CROSSLINKING COMONOMERS FOR HIGH PERFORMANCE DEGRADABLE THERMOSETS
20230416283 · 2023-12-28
Assignee
Inventors
Cpc classification
International classification
C07F7/18
CHEMISTRY; METALLURGY
Abstract
The present disclosure provides compounds of the formula (I): The present disclosure also provides copolymers prepared by polymerizing a first monomer (e.g., dicyclopentadiene) and the compounds. The copolymers may show increased degradability and increased or maintained glass-transition temperature, as compared to homopolymers of the first monomer.
##STR00001##
Claims
1. A compound of Formula (B): ##STR00057## or a salt thereof, wherein: W is carbon or silicon; Y is O or C(R.sup.Q).sub.2; each instance of R.sup.Q is independently hydrogen, halogen, or substituted or unsubstituted, C.sub.1-6 alkyl; each instance of R.sup.Y is independently hydrogen, halogen, or substituted or unsubstituted, C.sub.1-6 alkyl; each instance of R.sup.Z is independently hydrogen, halogen, or substituted or unsubstituted, C.sub.1-6 alkyl; R.sup.K1 is hydrogen, halogen, substituted or unsubstituted, C.sub.1-10 alkyl, substituted or unsubstituted, C.sub.2-10 alkenyl, substituted or unsubstituted, C.sub.2-10 alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, -L.sup.K1-(substituted or unsubstituted carbocyclyl), -L.sup.K1-(substituted or unsubstituted heterocyclyl), -L.sup.K1-(substituted or unsubstituted aryl), -L.sup.K1-(substituted or unsubstituted heteroaryl), or OR.sup.N1; L.sup.K1 is O, substituted or unsubstituted, alkylene, substituted or unsubstituted, C.sub.2-10 heteroalkylene, substituted or unsubstituted carbocyclylene, substituted or unsubstituted heterocyclylene, substituted or unsubstituted arylene, substituted or unsubstituted heteroarylene, or a combination thereof; R.sup.N1 is independently hydrogen, substituted or unsubstituted acyl, substituted or unsubstituted, C.sub.1-10 alkyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, or an oxygen protecting group; R.sup.K2 is halogen, substituted or unsubstituted, C.sub.2-10 alkenyl, substituted or unsubstituted C.sub.2-10 alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted heteroaryl, -L.sup.K2-(substituted or unsubstituted carbocyclyl), -L.sup.K2-(substituted or unsubstituted heterocyclyl), -L.sup.K2-(substituted or unsubstituted aryl), or OR.sup.N2-; L.sup.K2 is O, substituted or unsubstituted, C.sub.1-10 alkylene, substituted or unsubstituted, C.sub.2-10 heteroalkylene, substituted or unsubstituted carbocyclylene, substituted or unsubstituted heterocyclylene, substituted or unsubstituted arylene, substituted or unsubstituted heteroarylene, or a combination thereof; R.sup.N2 is independently hydrogen, substituted or unsubstituted acyl, substituted or unsubstituted, C1-io alkyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, or an oxygen protecting group; or R.sup.K1 and R.sup.K2 are joined with the intervening atom to form substituted or unsubstituted carbocyclyl or substituted or unsubstituted heterocyclyl; j is 1, 2, or 3; and k is 1, 2, or 3; provided that the compound is not of the formula: ##STR00058##
2. The compound of claim 1, or a salt thereof, provided that the compound is not of the formula: ##STR00059##
3-65. (canceled)
66. The compound of claim 1, or a salt thereof, wherein the compound is of the formula: ##STR00060##
67. The compound of claim 1, or a salt thereof, wherein the compound is of the formula: ##STR00061##
68. The compound of claim 1, or a salt thereof, wherein the compound is of the formula: ##STR00062##
69. A copolymer prepared by a method comprising polymerizing: one or more instances of a first monomer; one or more instances of a second monomer, wherein the second monomer is a compound of claim 1, or a salt thereof; and optionally one or more instances of a third monomer; wherein any two instances of the first monomer are the same as or different from each other, any two instances of the second monomer are the same as or different from each other, any two instances of the third monomer are the same as or different from each other, and each instance of the first monomer, the second monomer, and the third monomer if present, is different from each other; in the presence of a metathesis catalyst.
70. A method of preparing a copolymer of claim 69 comprising polymerizing: one or more instances of a first monomer; one or more instances of a second monomer, wherein the second monomer is a compound of claim 1, or a salt thereof; and optionally one or more instances of a third monomer; wherein any two instances of the first monomer are the same as or different from each other, any two instances of the second monomer are the same as or different from each other, any two instances of the third monomer are the same as or different from each other, and each instance of the first monomer, the second monomer, and the third monomer if present, is different from each other; in the presence of a metathesis catalyst.
71. A hydroxylated oligomer or hydroxylated polymer prepared by a method comprising hydrolyzing a copolymer of claim 69, wherein the step of hydrolyzing the copolymer comprises hydrolyzing one or more instances of the OSi bonds of the copolymer to form OH.
72. A method of preparing a hydroxylated oligomer or hydroxylated polymer comprising hydrolyzing a copolymer of claim 69, wherein the step of hydrolyzing the copolymer comprises hydrolyzing one or more instances of the OSi bonds of the copolymer to form OH.
73-100. (canceled)
101. A conjugate prepared by reacting a hydroxy-reacting substance with a hydroxylated oligomer or hydroxylated polymer of claim 71, wherein hydroxy-reacting substance comprises at least one instance of a hydroxy-reacting moiety.
102. A method of preparing a conjugate comprising reacting a hydroxy-reacting substance with a hydroxylated oligomer or hydroxylated polymer of claim 71.
103-109. (canceled)
110. A composition comprising: a compound of claim 1, of a salt thereof; and optionally an excipient.
111. A kit comprising: a compound of claim 1, or a salt thereof; and instructions for using the compound or salt.
112. A composition comprising: a copolymer of claim 69; and optionally an excipient.
113. A composition comprising: a hydroxylated oligomer or hydroxylated polymer of claim 71; and optionally an excipient.
114. A composition comprising: a conjugate of claim 101; and optionally an excipient.
115. A kit comprising: a copolymer of claim 69; and instructions for using the copolymer.
116. A kit comprising: a hydroxylated oligomer or hydroxylated polymer of claim 71; and instructions for using the hydroxylated oligomer or hydroxylated polymer.
117. A kit comprising: a conjugate of claim 101; and instructions for using the conjugate.
Description
BRIEF DESCRIPTION OF THE DRAWINGS
[0066] The figures are exemplary and do not limit the scope of the present disclosure.
[0067]
[0068]
[0069]
[0070]
[0071]
[0072]
[0073]
[0074]
[0075]
[0076]
[0077]
[0078]
[0079]
[0080]
[0081]
DETAILED DESCRIPTION OF CERTAIN EMBODIMENTS OF THE DISCLOSURE
[0082] The present disclosure provides the subject matter described herein, e.g., subject matter described in the claims. For example, the present disclosure provides compounds, copolymers, hydroxylated oligomers, hydroxylated polymers, conjugates, compositions, kits, methods of preparing the compounds, methods of preparing the hydroxylated oligomers and hydroxylated polymers, methods of preparing the copolymers, and methods of preparing the conjugates.
[0083] The compounds may be useful for preparing the copolymers, In certain embodiments, the compounds are second monomers (second comonomers) for preparing the copolymers. In certain embodiments, the first monomers (first comonomers) are dicyclopenta.diene (DCPD). Ring opening metathesis polymerization (ROMP) may be employed, in the presence of a metathesis catalyst, to prepare the copolymers. The copolymers may be thermosetting polymers. Thermosetting polymers are typically difficult to be recycled. The copolymers may be degradable (e.g., biodegradable). In certain embodiments, one or more OSi or OC bonds of the copolymers are the degradation sites. In certain embodiments, the presence of the second monomers in the preparation of the copolymers increase the degradability of the copolymers.
[0084] It may be desirable to increase or maintain the glass-transition temperature (T.sub.g) of the copolymers while the degradability of the copolymers is increased. In certain embodiments, the presence of the second monomers in the preparation of the copolymers increase the T.sub.g of the copolymers. In certain embodiments, the presence of the second monomers in the preparation of the copolymers do not significantly decrease the T.sub.g of the copolymers. In certain embodiments, the second monomers are crosslinking monomers, e.g., monomers with two or more polymerization handles (e.g., ROMP handles). in certain embodiments, the presence of the crosslinking monomers in the preparation of the copolymers increase the T. of the copolymers. In certain embodiments, the presence of the crosslinking monomers in the preparation of the copolymers do not significantly decrease the T.sub.g of the copolymers.
[0085] The hydroxylated oligomers and hydroxylated polymers may be degradation (e.g., hydrolysis) products of the copolymers. The hydroxylated oligomers and hydroxylated polymers may be soluble in, e.g., commercially available solvents (e.g., THF). The hydroxylated oligomers and hydroxylated polymers may be useful for recycling the copolymers. The hydroxylated oligomers and hydroxylated polymers may be useful as starting materials for preparing additional oligomers or polymers.
[0086] In one aspect, the present disclosure provides compounds of Formula (B):
##STR00003##
and salts thereof, wherein:
[0087] W is carbon or silicon;
[0088] Y is O or C(R.sup.Q).sub.2;
[0089] each instance of R.sup.Q is independently hydrogen, halogen, or substituted or unsubstituted, C.sub.1-6 alkyl;
[0090] each instance of R.sup.Y is independently hydrogen, halogen, or substituted or unsubstituted, C.sub.1-6 alkyl;
[0091] each instance of R.sup.Z is independently hydrogen, halogen, or substituted or unsubstituted, C.sub.1-6 alkyl;
[0092] R.sup.K1 is hydrogen, halogen, substituted or unsubstituted, C.sub.1-10 alkyl, substituted or unsubstituted, C.sub.2-10 alkenyl, substituted or unsubstituted, C.sub.2-10alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, L.sup.K1-(substituted or unsubstituted carbocyclyl),-L.sup.K1-(substituted or unsubstituted heterocyclyl), -L.sup.K1-(substituted or unsubstituted aryl), 1L.sup.K1-(substituted or unsubstituted heteroaryl), or OR.sup.N1;
[0093] L.sup.K1 is O, substituted substituted or unsubstituted, C.sub.1-10 alkylene, substituted or unsubstituted, C.sub.2-10 heteroalkylene, substituted or unsubstituted carbocyclyiene, substituted or unsubstituted heterocyclylene, substituted or unsubstituted arylene, substituted or unsubstituted heteroarylene, or a combination thereof;
[0094] R.sup.N1 is independently hydrogen, substituted or unsubstituted acyl, substituted or unsubstituted, C.sub.1-10 alkyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, or an oxygen protecting group;
[0095] R.sup.K2 is halogen, substituted or unsubstituted, C.sub.2-10 alkenyl, substituted or unsubstituted, C.sub.2-10 alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted heteroaryl, -L.sup.K2-(substituted or unsubstituted carbocyclyl), -L.sup.K2-(substituted or unsubstituted aryl), or OR.sup.N2,
[0096] L.sup.K2 is O, substituted or unsubstituted, C.sub.1-10alkylene, substituted or unsubstituted, C.sub.2-10 heteroalkylene, substituted or unsubstituted carbocyclylene, substituted or unsubstituted heterocyclylene, substituted or unsubstituted arylene, substituted or unsubstituted heteroarylene, or a combination thereof;
[0097] R.sup.N2 is independently hydrogen, substituted or unsubstituted acyl, substituted or unsubstituted, Cr-to alkyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, or an oxygen protecting group;
[0098] or R.sup.K1 and R.sup.2 are joined with the intervening atom to form substituted or unsubstituted carbocyclyl or substituted or unsubstituted heterocyclyl;
[0099] j is 1, 2, or 3; and [0100] k is 1, 2, or 3;
provided that the compound is not of the formula:
##STR00004##
[0101] In certain embodiments, the compound is not of the formula:
##STR00005##
[0102] In certain embodiments, the compound comprises one non-aromatic CC or non-aromatic CC bond. In certain embodiments, the compound comprises two, three, or four non-aromatic CC and/or non-aromatic CC bonds,:ln certain embodiments, the compound comprises two (i.e., only two) non-aromatic CC and/or non-aromatic CC bonds, In certain embodiments, the compound comprises only three non-aromatic CC and/or non-aromatic CC bonds (i.e., the combined number of non-aromatic CC bonds and non-aromatic CC bonds is three). In certain embodiments, the compound comprises no CEEC bonds.
[0103] In certain embodiments, the compound is of the formula:
##STR00006##
or a salt thereof.
[0104] In certain embodiments, the compound is of the formula:
##STR00007##
or a salt thereof.
[0105] In certain embodiments, the compound is of the formula:
##STR00008##
or a salt thereof.
[0106] In certain embodiments, the compound is of the formula:
##STR00009##
or a salt thereof.
[0107] In certain embodiments, the compound is of the formula:
##STR00010##
or a salt thereof.
[0108] In certain embodiments, the compound is of the formula:
##STR00011##
or a salt thereof, wherein:
[0109] each instance of Y is independently O or C(R.sup.Q).sub.2;
[0110] each instance of R.sup.Q is independently hydrogen, halogen, or substituted or unsubstituted, C.sub.1-6 alkyl;
[0111] each instance of R.sup.Y is independently hydrogen, halogen, or substituted or unsubstituted, C.sub.1-6 alkyl;
[0112] each instance of R.sup.Z is independently hydrogen, halogen, or substituted or unsubsti ted, C.sub.1-6 alkyl;
[0113] j is 1, 2, or 3; and
[0114] k is 1, 2, or 3.
[0115] The compound of claim 7, or a salt thereof, wherein the compound is of the formula:
##STR00012##
or a salt thereof.
[0116] The compound of claim 7, or a salt thereof, wherein the compound is of the formula:
##STR00013##
or a salt thereof.
[0117] The compound of claim 7, or a salt thereof, wherein the compound is of the formula:
##STR00014##
or a salt thereof.
[0118] In certain embodiments, each instance of Y is O. In certain embodiments, one instance of Y is CH.sub.2, and the other instance of Y is O.
[0119] In certain embodiments, each instance of R.sup.Q is hydrogen.
[0120] In certain embodiments, each instance of R.sup.Y is hydrogen. In certain embodiments, each instance of R.sup.Y is independently hydrogen or unsubstituted C.sub.1-6 alkyl. In certain embodiments, at least one instance of R.sup.Y is substituted or unsubstituted, C.sub.1-6 alkyl.
[0121] In certain embodiments, each instance of R.sup.Z is hydrogen. In certain embodiments, each instance of is independently hydrogen or unsubstituted C1-6 alkyl. In certain embodiments, at least one instance of R.sup.Z is substituted or unsubstituted, C.sub.1-6 alkyl.
[0122] In certain embodiments, j is 1, and k is 1. in certain embodiments, j is I, and k is 2. In certain embodiments, j is 1, and k is 3. In certain embodiments, j is 2, and k is 2. In certain embodiments, j is 2, and k is 3.
[0123] In certain embodiments, W is carbon. in certain embodiments, W is silicon.
[0124] In certain embodiments, Y is O. In certain embodiments, Y is CH.sub.2.
[0125] In certain embodiments, each instance of R.sup.Q is hydrogen.
[0126] In certain embodiments, each instance of R.sup.Y is hydrogen. In certain embodiments, each instance of R.sup.Y is independently hydrogen or unsubstituted C.sub.1-6 alkyl. In certain embodiments, at least one instance of R.sup.Y is substituted or unsubstituted, C.sub.1-6 alkyl.
[0127] In certain embZdiments, each instance of R.sup.Y is hydrogen. In certain embodiments, each instance of R.sup.Y is independently hydrogen or unsubstituted C.sub.1-6 alkyl. In certain embodiments, at least one instance of R.sup.Zis substituted or unsubstituted, C.sub.1-6 alkyl.
[0128] In certain embodiments, j is 1, and k is 1. In certain embodiments, j is 1, and k is 2. In certain embodiments, j is 1, and k is 3. In certain embodiments, j is 2, and k is 2. In certain embodiments, j is 2, and k is 3.
[0129] In certain embodiments, R.sup.K1 is substituted or unsubstituted, C.sub.1-10 alkyl, substituted or unsubstituted, C.sub.2-10 alkenyl, substituted or unsubstituted, C.sub.2-10 alkenyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, -L.sup.K1-(substituted or unsubstituted carbocyclyl), -L.sup.K1-(substituted or unsubstituted heterocyclyl), -L.sup.K1-(substituted or unsubstituted aryl), -L.sup.K1-(substituted or unsubstituted heteroaryll), or OR.sup.N1.
[0130] In certain embodiments, R.sup.K1 is substituted or unsubstituted, C.sub.1-10 alkyl. In certain embodiments, R.sup.K1 is unsubstituted methyl, unsubstituted ethyl, unsubstituted propyl (e.g., unsubstituted n-propyl or unsubstituted isopropyl), or unsubstituted butyl (e.g., unsubstituted butyl).
[0131] In certain embodiments, R.sup.K1 is substituted or unsubstituted, saturated carbocyclyl. In certain embodiments, R.sup.K1 is unsubstituted cyclopropyl, unsubstituted cyclobutyl, unsubstituted cyclopentyl, unsubstituted cyclohexyl, or unsubstituted cycloheptyl.
[0132] In certain embodiments, R.sup.K1 is substituted or unsubstituted, partially unsaturated carbocyclyl, in certain embodiments, R.sup.K1 is substituted or unsubstituted carbocyclyl that comprises only one unsaturated bond in the carbocyclic ring system. In certain embodiments, R.sup.K1 is unsubstituted cyclobutenyl, unsubstituted cyclopentenyl, unsubstituted cyclohexenyl, or unsubstituted cycloheptenyl. In certain embodiments, R.sup.K1 is substituted or unsubstituted carbocyclyl that comprises only two unsaturated bonds in the carbocyclic ring system. In certain embodiments, R.sup.K1 is substituted or unsubstituted carbocyclyl that comprises no Cbonds in the carbocyclic ring system.
[0133] In certain embodiments, R.sup.K1 is:
##STR00015##
wherein:
##STR00016##
is Ring B, wherein Ring B is a substituted or unsubstituted, monocyclic carbocyclic ring, substituted or unsubstituted, monocyclic heterocyclic ring, substituted or unsubstituted, monocyclic aryl ring, or substituted or unsubstituted, monocyclic heteroaryl ring;
[0134] Z is C(R.sup.P).sub.2 or O;
[0135] each instance of R.sup.P is independently hydrogen, halogen, or substituted or unsubstituted, C.sub.1-6 alkyl;
[0136]
is a single bond or double bond; each instance of R.sup.H is independently hydrogen, halogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, OR.sup.a, OCN, OC(O)R.sup.a, OC)S)R.sup.a, OC(O)OR.sup.4, OC(O)N(R.sup.a).sub.2, OS(O)R.sup.1, OS(O)R.sup.3, OS(O)OR.sup.a, OS(O)N(R.sup.a).sub.2, OS(O).sub.2R.sup.a, OS(O).sub.2OR.sup.a, OS(O).sub.2N(R.sup.3).sub.2, OSi((R.sup.a). OSi(R.sup.a).sub.2(OR.sup.a), OSi(R.sup.3)(OR.sup.3).sub.2, OSi(OR.sup.3).sub.3, oxo, N(R.sup.a).sub.3, NC(R.sup.a).sub.2, NR.sup.a, NC, NCO, N.sub.3, NO.sub.2, NR.sup.aC(O)R.sup.a, NR.sup.aC(O)OR.sup.3, NR.sup.aC(O)N(R.sup.a.sub.2, NR.sup.aS(O)R.sup.a, NR.sup.aS(O)OR.sup.a, NR.sup.aS(O)OR.sup.a, NR.sup.aS(O)N(R.sup.a).sub.2, NR.sup.aNR.sup.3S(O).sub.2R.sup.a, NR.sup.aS(O).sub.2OR.sup.a, NR.sup.aS(O).sub.2N(R.sup.a).sub.2, SR.sup.a, SCN, S(O)R.sup.a, S(O)OR.sup.a, S(O)N(R.sup.3).sub.2, S(O).sub.2R.sup.a, S(O).sub.2OR.sup.a, S(O).sub.2N(R.sup.a.sub.2; SeR.sup.a, SeR.sup.a, halogen, CN, C(NR.sup.a(R.sup.a, C(NR.sup.a)OR.sup.a, C(NR.sup.a)OR.sup.a, C(NR.sup.a)N(R.sup.a), C(O)R.sup.a), C(O)OR.sup.a, C(O)SR.sup.a, C(S)OR.sup.a, or C(O)N(R.sup.a).sub.2;
[0137] or the two instances of R.sup.H are ioined with the intervening carbon atoms to form a substituted or unsubstituted, monocyclic carbocyclic ring, substituted or unsubstituted, monocyclic heterocyclic ring, substituted or unsubstituted, monocyclic aryl ring, or substituted or unsubstituted, monocyclic heteroaryl ring; and
[0138] each instance of R.sup.a is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted, monocyclic carbocyclyl, substituted or unsubstituted, monocyclic heterocyclyl, substituted or unsubstituted, monocyclic aryl, substituted or unsubstituted, monocyclic heteroaryl, a nitrogen protecting group when attached to a nitrogen atom, an oxygen protecting group when attached to an oxygen atom, or a sulfur protecting group when attached to a sulfur atom, or two instances of R.sup.a are joined to form substituted or unsubstituted heterocyclyl or substituted or unsubstituted heteroaryl.
[0139] In certain embodiments, R.sup.K1 is:
##STR00017##
[0140] In certain embodiments, Ring B is substituted or unsubstituted, monocyclic carbocyclic ring. In certain embodiments, Ring B is substituted or unsubstituted, monocyclic, saturated carbocyclyl. In certain embodiments, Ring B is unsubstituted cyclopropyl, unsubstituted cyclobutyl, unsubstituted cyclopentyl, unsubstituted cyclohexyl, or unsubstituted cycloheptyl. In certain embodiments, Ring B is substituted or - unsubstituted, monocyclic, partially unsaturated carbocyclyl. In certain embodiments, Ring B is substituted or unsubstituted, monocyclic carbocyclyl that comprises only one unsaturated bond in the carbocyclic ring system. In certain embodiments, Ring B is unsubstituted cyclobutenyl, unsubstituted cyclopentenyl, unsubstituted cyclohexenyl, or unsubstituted cycloheptenyl. in certain embodiments, Ring B is substituted or unsubstituted, monocyclic carbocyclyl that comprises only two unsaturated bonds in the carbocyclic ring system. in certain embodiments, Ring B is substituted or unsubstituted, monocyclic carbocyclyl that comprises no CC bonds in the carbocyclic ring system.
[0141] In certain embodiments, Z is CH.sub.2.
[0142] In certain embodiments, each R.sup.H is hydrogen. In certain embodiments, two instances of R.sup.H are joined with the intervening carbon atoms to form an unsubstituted monocyclic carbocyclic ring. In certain embodiments, two instances R.sup.H are joined with the intervening carbon atoms to form an unsubstituted monocylic heterocyclic ring.
[0143] In certain embodiments, R.sup.K1 is
##STR00018##
[0144] In certain embodiments, R.sup.K1 is -(substituted or unsubstituted, C.sub.1-10 alkylene)-(substituted or unsubstituted, partially saturated carbocyclyl). In certain embodiments, R.sup.K1 is -(unsubstituted C140 alkylene)-(substituted or unsubstituted carbocyclyl that comprises only one unsaturated bond in the carbocyclic ring system). In certain embodiments, R.sup.H is substituted or unsubstituted heterocyclyl or L.sup.K1-(substituted or unsubstituted heterocyclyl). In certain embodiments, R.sup.K1 is substituted or unsubstituted heterocyclyl that comprises OSi in the heterocyclic ring system or -L.sup.K1-(substituted or unsubstituted heterocyclyl that comprises OSi in the heterocyclic ring system). In certain embodiments, R.sup.K1 is -(substituted or unsubstituted, C.sub.1-10 alkylene)-(substituted ter unsubstituted heterocyclyl). In certain embodiments, R.sup.K1 is (substituted or unsubstituted, C.sub.1-10 alkylene)-substituted or unsubstituted heterocyclyl that comprises OSi in the heterocyclic ring system). In certain embodiments, R.sup.K1 is:
##STR00019##
In certain embodiments, R.sup.K1 is -(substituted or unsubstituted phenylene)-(substituted or unsubstituted, partially saturated heterocyclyl). In certain embodiments, R.sup.K1 is -(substituted or unsubstituted phenylene)-(substituted or unsubstituted heterocyclyl that comprises only one unsaturated bond in the heterocyclic ring system). In certain embodiments, R.sup.K1 is -(substituted or unsubstituted phenylene)-(substituted or unsubstituted, partially saturated heterocyclyl that comprises OSi in the heterocyclic ring system). In certain embodiments, R.sup.K1 is -(substituted or unsubstituted phenylene)-(substituted or unsubstituted heterocyclyl that comprises OSi and only one unsaturated bond in the heterocyclic ring system).
[0145] In certain embodiments, R.sup.K1 is
##STR00020##
In certain embodiments, R.sup.K1 is
##STR00021##
In certain embodiments, R.sup.K1 is
##STR00022##
[0146] In certain embodiments, R.sup.K1 is hydrogen. In certain embodiments, R.sup.K1 is OR.sup.N1.
[0147] In certain embodiments, R.sup.N1 is substitued or unsubstituted, C.sub.1-10 alkyl. In certain embodiments, R.sup.N1 is unsubstituted C.sub.1-2 alkyl.
[0148] In certain embodiments, R.sup.K2 is substituted or unsubstituted, C.sub.1-10 alkylene. In certain embodiments, L.sup.K1 is unsubstituted. C.sub.1-10 alkylene. In certain embodiments, L.sup.K3 is substituted or unsubstituted phenylene. In certain embodiments, R.sup.K2 is substituted or unsubstituted, saturated carbocyclyl. In certain embodiments, R.sup.K2 is unsubstituted cyclopropyl, unsubstituted cyclobutyl, unsubstituted cyclopentyl, unsubstituted cyclohexyl, or unsubstituted cycloheptyl.
[0149] In certain embodiments, R.sup.K2 is substituted or unsubstituted, partially unsaturated carbocyclyl. In certain embodiments, R.sup.K2 is substituted or unsubstituted carbocyclyl that commises only one unsaturated bond in the carbocyclic ring system. In certain embodiments, R.sup.K2 is unsubstituted cyclobutenyl, unsubstituted cyclopentenyl, unsubstituted cyclobexenyl, or unsubstituted cycloheptenyl. In certain embodiments, R.sup.K2 is substituted or unsubstituted carbocyclyl that comprises only two unsaturated bonds in the carbocyclic ring system. In certain embodiments, R.sup.K1 is substituted or unsubstituted carbocyclyl that comprises no CC bonds in the carbocyclic ring system.
[0150] in certain embodiments, R.sup.K2 is:
##STR00023##
wherein:
##STR00024##
is Ring B, wherein Ring B is a substituted or unsubstituted, monocyclic carbocyclic ring, substituted or unsubstituted, monocyclic heterocyclic ring, substituted or unsubstituted, monocyclic aryl ring, or substituted or unsubstituted, tnonocydic heteroaryl ring;
[0151] Z is C(R.sup.P).sub.2 or O;
[0152] each instance of R.sup.P is independently hydrogen, halogen, or substituted or unsubstituted, C.sub.1-6 alkyl;
[0153] is a single bond or double bond;
[0154] each instance of R.sup.H is independently hydrogen, halogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, OR.sup.a, OCN, OC(O)R.sup.a, OC(S)R.sup.a, OC(O)OR.sup.a, OC(O)N(R.sup.a).sub.2, OS(O)R.sup.a, OS(O)OR.sup.a, OS(O)N(R.sup.a).sub.2, OS(O).sub.2R.sup.a, OS(O).sub.2OR.sup.a, OS(O).sub.2N(R.sup.a).sub.2, OSi(R.sup.a).sub.2, OSi(R.sup.a).sub.2(OR.sup.a), OSi(R.sup.a)(OR.sup.a).sub.2, OSi(OR.sup.a)(OR.sup.a).sub.2, OSi(OR.sup.a).sub.3, oxo, N(R.sup.a).sub.2, NC(R.sup.a).sub.2, NR.sup.a, NC, NCO, N.sub.3, NO.sub.2, NR.sup.aC(O)R.sup.a, NR.sup.aC(O)(OR.sup.a, NR.sup.aC(O)N(R.sup.a).sub.2, NR.sup.aS(O)R.sup.a, NR.sup.aS(O)OR.sup.a, NR.sup.aS(O)N(R.sup.a).sub.2, NR.sup.aS(O).sub.2R.sup.a, NR.sup.aS(O).sub.2OR.sup.a, NR.sup.aS(O).sub.2, N(R.sup.a).sub.2, SR.sup.a, SCN, S(O)R.sup.a, S(O)OR.sup.a, S(O)N(R.sup.a, C(NR.sup.a)N(R.sup.a), C(O)R.sup.a, CO(R.sup.a, C(O)OR.sup.a, C(O)SR.sup.a, C(S)OR.sup.a, or C(O)N(R.sup.a).sub.2;
[0155] or the two instances of R.sup.H+ are kpomed wotj tje omtervemomg carbpm atp,s tp fpr, a substituted or unsubstituted, monocyclic carbocyclic ring, substituted or unsubstituted, monocyclic heterocyclic ring, substituted or unsubstituted, monocyclic aryl ring, or substituted or unsubstituted, monocyclic heteroaryl ring; and
[0156] each instance of R.sup.a is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted, monocyclic carbocyclyl, substituted or unsubstituted, monocyclic heterocyclyl, substituted or unsubstituted, monocyclic aryl, substituted or unsubstituted, monocyclic heteroaryl, a nitrogen protecting group when attached to a nitrogen atom, an oxygen protecting group when attached to an oxygen atom, or a sulfur protecting group when attached to a sulfur atom, or two instances of R.sup.a are joined to form substituted or unsubstituted heterocyclyl or substituted or unsubstituted heteroaryl,
[0157] In certain embodiments, R.sup.K2 is:
##STR00025##
[0158] In certain embodiments, :Ring B is substituted or unsubstituted, monocyclic carbocyclic ring. In certain embodiments, Ring B is substituted or unsubstituted, monocyclic, saturated carbocyclyl. In certain embodiments, Ring B is unsubstituted cyclopropyl, unsubstituted cyclobutyl, unsubstituted. cyclopentyl, unsubstituted cyclohexyl, or unsubstituted cycloheptyl. In certain embodiments, Ring B is substituted or unsubstituted, monocyclic, partially unsaturated carbocyclyl. In certain embodiments, Ring B is substituted or unsubstituted, monocyclic carbocyclyl that comprises only one unsaturated bond in the carbocyclic ring system. In certain embodiments, Ring B is unsubstituted unsubstituted cyclopentenyl, unsubstituted cyclohexenyl, or unsubstituted cycloheptenyl. In certain embodiments, Ring B is substituted or unsubstituted, monocyclic carbocyclyl that comprises only two unsaturated bonds in the carbocyclic ring system. In certain embodiments, Ring B is substituted or unsubstituted, monocyclic carbocyclyl that comprises no CC bonds in the carbocyclic ring system.
[0159] In certain embodiments, Z is CH.sub.2.
[0160] In certain embodiments, each R.sup.H is hydrogen. In certain embodiments, two instances of R.sup.H are joined with the intervening carbon atoms to form an unsubstituted monocyclic carbocyclic ring. In certain embodiments, two instances of R.sup.H are joined with the intervening carbon atoms to form an unsubstituted monocylic heterocyclic ring.
[0161] In certain embodiments, R.sup.K2 is
##STR00026##
[0162] In certain embodiments, R.sup.K2 is (substituted or unsubstituted, C.sub.1-10 alkylene)-(substituted or unsubstituted, partially saturated carbocyclyl). In certain embodiments, R.sup.K2 is -(unsubstituted C140 alkylene)(substituted or unsubstituted carbocyclyl that comprises only one unsaturated bond in the carbocyclic ring system).
[0163] In certain embodiments, R.sup.K2 is substituted or unsubstituted heterocyclyl or (substituted or unsubstituted heterocyclyl). In certain embodiments, R.sup.K2 is substituted or unsubstituted heterocyclyl that comprises OSi in the heterocyclic ring system or -L.sup.K2-(substituted or unsubstituted heterocyclyl that comprises OSi in the heterocyclic ring system). In certain embodiments, R.sup.K2 is -(substituted or unsubstituted, C.sub.1-10 alkylene)-(substituted or unsubstituted heterocyclyl). In certain embodiments, R.sup.K2 -(substituted or unsubstituted, C.sub.1-10 alkylene)--substituted or unsubstituted heterocyclyl that comprises OSi in the heterocyclic ring system). In certain embodiments, R.sup.K2 is:
##STR00027##
In certain embodiments, R.sup.K2 is -(substituted or unsubstituted phenylene)-(substituted or unsubstituted, partially saturated heterocyclyl). In certain embodiments, R.sup.K2 is -(substituted or unsubstituted phenylene)-(substituted or unsubstituted heterocyclyl that comprises only one unsaturated bond in the heterocyclic ring system). In certain embodiments, R.sup.K2 is -(substituted or unsubstituted phenylene)-(substituted or unsubstituted, partially saturated heterocyclyl that comprises OSi in the heterocyclic ring system). In certain embodiments, R.sup.K2 is -(substituted or unsubstituted phenylene)-(substituted or unsubstituted heterocyclyl that comprises OSi and only one unsaturated bond in the heterocyclic ring system).
[0164] In certain embodiments, R.sup.K2 is
##STR00028##
In certain embodiments, R.sup.K2 is
##STR00029##
In certain embodiments, R.sup.K2 is
##STR00030##
[0165] In certain embodiments, R.sup.K2 is hydrogen. in certain embodiments, R.sup.K2 is OR.sup.N2.
[0166] In certain embodiments, R.sup.N2 is substituted or unsubstituted, C.sub.1-10 alkyl. In certain embodiments, R.sup.N2 is unsubstituted C.sub.1-6 alkyl.
[0167] In certain embodiments, L.sup.K2 is O or substituted or unsubstituted, C.sub.1-10 alkylene. In certain embodiments, L.sup.K2 is unsubstituted C.sub.1-6 alkylene. In certain embodiments, L.sup.K2 is substituted or unsubstituted phenylene.
[0168] In certain embodiments, R.sup.K1 and R.sup.K2 are joined with the intervening atom to form substituted or unsubstituted, partially unsaturated carbocyclyl. In certain embodiments, R.sup.K1 and R.sup.K2 are joined with the intervening atom to form substituted or unsubstituted, monocyclic carbocyclyl that comprises only one unsaturated bond in the carbocyclic ring system. In certain embodiments, R.sup.K1 and R.sup.K2 are joined with the intervening atom to form unsubstituted cyclobutenyl, unsubstituted cyclopentenyl, unsubstituted cyclohexenyl, or unsubstituted cycloheptenyl. In certain embodiments, R.sup.K1 and R.sup.K2 are joined with the intervening atom to form substituted or unsubstituted, monocyclic carbocyclyl that comprises only two unsaturated bonds in the carbocyclic ring system. In certain embodiments, R.sup.K1and R.sup.K2 are joined with the intervening atom to form substituted or unsubstituted carbocyclyl that comprises no CC bonds in the carbocyclic ring system.
[0169] In certain embodiments, R.sup.K1 and R.sup.K2 are joined with the intervening atom to form substituted or unsubstituted, partially unsaturated heterocyclyi. In certain embodiments, R.sup.K1 and R.sup.K2 are joined with the intervening atom to form substituted or unsubstituted, monocyclic heterocyclyl that comprises only one unsaturated bond in the heterocyclic ring system. In certain embodiments, R.sup.K1 and R.sup.K2 are joined with the intervening atom to form substituted or unsubstituted, monocyclic heterocyclyl that comprises only two unsaturated bonds in the heterocyclic ring system. In certain embodiments, R.sup.K1 and R.sup.K2 are joined with the intervening atom to form substituted or unsubstituted heterocyclyl that comprises no CC bonds in the heterocyclic ring system.
[0170] In certain embodiments, the CC bond in the heterocyclic ring that comprises OWY is of the (Z)-configuration. In certain embodiments, the CC bond in the heterocyclic ring that comprises OWY is of the (F)-configuration.
[0171] In certain embodiments, the compound is of the formula:
##STR00031##
or a salt thereof.
[0172] In certain embodiments, the compound is of the formula:
##STR00032##
or a salt thereof.
[0173] In certain embodiments, the compound is of the formula:
##STR00033##
or a salt thereof.
[0174] In certain embodiments, a compound of the present disclosure is a compound of Formula (B), or a salt thereof.
[0175] In another aspect, the present disclosure provides copolymers (copolymers of the present disclosure) prepared by a method comprising polymerizing:
[0176] one or more instances of a first monomer;
[0177] one or more instances of a second monomer, wherein the second monomer is a compound of the present disclosure, or a salt thereof; and
[0178] optionally one or more instances of a third monomer;
[0179] wherein any two instances of the first monomer are the same as or different from each other, any two instances of the second monomer are the same as or different from each other, any two instances of the third monomer are the same as or different from each other, and each instance of the first monomer, the second monomer, and the third monomer if present, is different from each other;
[0180] in the presence of a metathesis catalyst.
[0181] In another aspect, the present disclosure provides methods of preparing a copolymer of the present disclosure comprising polymerizing:
[0182] one or more instances of a first monomer; one or more instances of a second monomer, whereine second monomer is a compound of the present disclosure, or a salt thereof; and
[0183] optionally one or more instances of a third monomer;
[0184] wherein any two instances of the first monomer are the same as or different from each other, any two instances of the second monomer are the same as or different from each other, any two instances of the third monomer are the same as or different from each other, and each instance of the first monomer, the second monomer, and the third monomer if present, is different from each other;
[0185] in the presence of a metathesis catalyst.
[0186] In another aspect, the present disclosure provides hydroxylated oligomers (hydroxylated oligomers of the present disclosure) or hydroxylated polymers (hydroxylated polymers of the present disclosure) prepared by a method comprising hydrolyzing a copolymer of the present disclosure, wherein the step of hydrolyzing the copolymer comprises hydrolyzing one or more instances of the OSi bonds of the copolymer to form OH.
[0187] In another aspect, the present disclosure provides methods of preparing a hydroxylated oligomer or hydroxylated polymer comprising hydrolyzing a copolymer of the present disclosure, wherein the step of hydrolyzing the copolymer comprises hydrolyzing one or more instances of the OSi bonds of the copolymer to form OH.
[0188] In certain embodiments, the step of polymerizing (Step (a)) is substantially free of solvents. In certain embodiments, Step (a) further comprises the presence of a solvent (e.g., organic solvent).
[0189] In certain embodiments, Step (a) is substantially free of a chain transfer agent.
[0190] In certain embodiments, the temperature of Step (a) is between 20 and 40, between 40 and 60, between 60 and 80, between 80 and 100, between 100 and 120, between 120 and 140, or between 140 and 160 C., inclusive, In certain embodiments, the temperature of Step (a) is between 100 and 140 C., inclusive.
[0191] In certain embodiments, the time duration of Step (a) is between 1 and 10 minutes, between 10 and 60 minutes, between 1 and 6 hours, between 6 and 24 hours, between 1 and 3 days, or between 3 and 7 days, inclusive. In certain embodiments, the time duration of Step (a) is between 10 minutes and 2 hours, inclusive.
[0192] In certain embodiments, the polymerizing of Step (a) is ROMP.
[0193] In certain embodiments, the method of preparing the copolymer further comprises (b) exposing the copolymer to a solvent.
[0194] In certain embodiments, the method of preparing the copolymer further comprises (c) solid-liquid phase separation. In certain embodiments, Step (c) is subsequent to Step (b).
[0195] In certain embodiments, the method of preparing the copolymer further comprises curing. In some embodiments, curing forms a resin. In certain embodiments, curing is carried out at 70 to 150 C., inclusive. In certain embodiments, curing is carried out at 100 to 150 C., inclusive. In certain embodiments, curing is carried out at 100 to 130 C., inclusive. In certain embodiments, curing is carried out at 110 to 120 C., inclusive. In some embodiments, curing is carried out at about 110 C. in some embodiments, curing is carried out at about 120 C. In some embodiments, curing is carried out for 1 minute to 3 hours, inclusive. In some embodiments, curing is carried out for 15 minutes to 1 hour, inclusive. In some embodiments, curing is carried out for 15 minutes. In certain embodiments, curing is carried out for 30 minutes. In some embodiments, curing is carried out for 1 hour. In certain embodiments, curing is carried out at ambient pressure. In some embodiments, curing is carried out at lower-than-ambient pressure. In some embodiments, curing is carried out at higher-than-ambient pressure.
[0196] The preparation of the copolymers may involve a metathesis reaction. In certain embodiments, the metathesis reaction is a ring-opening metathesis copolymerization (ROMP) (see, e.g., Liu el at Am. Chem. Soc. 2012, 134, 16337; Liu, J.; Gao, A. X.; Johnson, J. A. J Vis Exp 2013, e50874).
[0197] In certain embodiments, the metathesis catalyst (e.g., ROMP catalyst) is a tungsten (W), molybdenum (Mo), or ruthenium (Ru), metathesis catalyst. In certain embodiments, the metathesis catalyst is a ruthenium metathesis catalyst. Metathesis catalysts useful in the synthetic methods described herein include catalysts as depicted below, and as described in Grubbs et al., Acc. Chem, Res. 1995, 28, 446-452; U.S. Pat. No. 5,811,515; Schrock et al., Organometallics (1982) 1 1645; Gallivan et al., Tetrahedron Leiters (2005) 46:2577-2580; Furstner et al., J. Am. Chem, Soc. (1999) 121:9453; and Chem. Eur. J. (2001) 7:5299; the entire contents of each of which are incorporated herein by reference.
[0198] In certain embodiments, the metathesis catalyst is a Grubbs catalyst. In certain embodiments, the Grubbs catalyst is selected from the group consisting of:
##STR00034##
[0199] Benzylidenebis-(tricyclohexylphosphine)-dichlororutheniurn (XCl); Benzyliclenebis-(tricyclohexylphosphine)-dibromoruthenium (XBr); Benzylidenebis-(tricyclohexylphosphine)-diiodonithenium (XI);
##STR00035##
[0200] 1,3-(Bis(mesityl)-2-imidazolidinylidene)dichloro-(phenyhnethylene) (tricyclohexyl-phosphine)ruthenium (X Cl; R=cyclohexyl); 1,3-(Bis(mesityl)-2-imidazolidinylidene)dibromo-(phenyhnethylene) (tricyclohexyl-phosphine)nithertium (XBr; R=cyclohexyl); 1,3-(Bis(mesityl)-2-imidazolidinylidene)diiodo-(phenylmothylene) (tricyclohexyl-phosphine)rathenium (XI; R=cyclohexyl); 1,3-(Bis(mesityl)-2-imidiazolidinylidene)dichloro-(phenylmothylene) (triphenylphosphine)ruthenium (XCl; R=phenyl); 1,3-(Bis(mesityl)-2-imidazolidinylidene)dichloro-(phenylmethylene) (tribenzylphosphine)ruthenium (XCl; R=benzyl);
##STR00036##
[0201] In certain embodiments, the metathesis catalyst is a Grubbs-Hoveyda catalyst. In certain embodiments, the Grubbs-Hoveyda catalyst is selected from the group consisting of:
##STR00037##
[0202] In certain embodiments, t e metathesis catalyst is selected from the group consisting of:
##STR00038##
[0203] In certain embodiments, the metathesis catalyst is of the formula:
##STR00039##
[0204] In certain embodiments, the metathesis catalyst is the second-generation Grubbs catalyst. In certain embodiments, the ratio of the combined molar amounts of the first monomer, second monomer, and third monomer if present to the molar amount of the metathesis catalyst is not less than 1,000. In certain embodiments, the ratio of the combined molar amounts of the first monomer, second monomer, and third monomer if present to the molar amount of the metathesis catalyst is between 100 and 300, inclusive. In certain embodiments, the ratio of the combined molar amounts of the first monomer, second monomer, and third monomer if present to the molar amount of the metathesis catalyst is between 300 and 1,000, inclusive. in certain embodiments, the ratio of the combined molar amounts of the first monomer, second monomer, and third monomer if present to the molar amount of the metathesis catalyst is between 1,000 and 1,50, inclusive. In certain embodiments, the ratio of the combined molar amounts of the first monomer, second monomer, and third monomer if present to the molar amount of the metathesis catalyst is between 1,500 and 2,000, inclusive. In certain embodiments, the ratio of the combined molar amounts of the first monomer, second monomer, and third monomer if present to the molar amount of the metathesis catalyst is between 2,000 and 10,000, inclusive. In certain embodiments, the ratio of the combined molar amounts of the first monomer, second monomer. and third monomer if present to the molar amount of the metathesis catalyst is between 10,000 and 30,000, inclusive. In certain embodiments, the ratio of the combined molar amounts of the first monomer, second monomer, and third monomer if present to the molar amount of the metathesis catalyst is between 30,000 and 100,000, inclusive.
[0205] The ROMP can he conducted in one or more aprotic solvents. The term aprotic solvent means a non-nucleophilic solvent having a boiling point range above ambient temperature, preferably from about 25 C. to about 190 C. at atmospheric pressure. In certain embodiments, the aprotic solvent has a boiling point from about 80 C. to about 160 C. at atmospheric pressure. In certain embodiments, the aprotic solvent has a boiling point from about 80 C. to about 150 C. at atmospheric pressure. Examples of such solvents are methylene chloride, acetonitrile, toluene, DMF, diglyme, THF, and DMSO.
[0206] The ROMP can be quenched with a vinyl ether of the formula
##STR00040##
Each of R.sup.V1, R.sup.V2, R.sup.V3, and R.sup.V4 is independently optionally substituted alkyl, optionally substituted alkenyl, optionally substituted alkynyl, optionally substituted carbocyclyl, optionally substituted phenyl, optionally substituted heterocyclyl, or optionally substituted heteroaryl, In certain embodiments, R.sup.V1 is optionally substituted alkyl, and R.sup.V2, R.sup.V3, and R.sup.V4 are hydrogen. In certain embodiments, R.sup.V1 is unsubstituted alkyl, and R.sup.V2, R.sup.V3, and R.sup.V4 are hydrogen. In certain embodiments, R.sup.V1 is substituted alkyl, and R.sup.V2, R.sup.V3, and R.sup.V4 are hydrogen. In certain embodiments, R.sup.V1 is methyl, and R.sup.V2, R.sup.V3, and R.sup.V4 are hydrogen. In certain embodiments, R.sup.V1 is ethyl, and R.sup.V2, R.sup.V3, and R.sup.V4 are hydrogen. In certain embodiments, R.sup.V1 is propyl, and R.sup.V2, R.sup.V3, and R.sup.V4 are hydrogen. In certain embodiments, R.sup.V1 is optionally substituted alkenyl, and R.sup.V2, R.sup.V3, and R.sup.V4 are hydrogen. In certain embodiments, R.sup.V1 is unsubstituted alkenyl, and R.sup.V2, R.sup.V3, and R.sup.V4 are hydrogen. In certain embodiments, R.sup.V1 is vinyl, and R.sup.V2 and R.sup.V3, and R.sup.V4 are hydrogen. In certain embodiments, at least one of R.sup.V1, R.sup.V2, R.sup.V3, and R.sup.V4 is conjugated with a diagnostic agent as defined above. in certain embodiments, the ROMP is quenched by ethyl vinyl ether. Excess ethyl vinyl ether can be removed from the copolymer under reduced pressure.
[0207] In certain embodiments, at least two instances of a variable (e.g., a moiety) are different from each other. In certain embodiments, all instances of a variable are different from each other. In certain embodiments, all instances of a variable are the same. For example, when a compound, copolymer, hydroxylated oligomer, or hydroxylated polymer comprises two or more instances of a moiety, any two instances of the moiety may be the same or different from each other, unless otherwise provided. For example, when a compound of Formula (B) comprises two instances of R.sup.K1, the two instances of R.sup.K1 may be the same or different from each other.
[0208] In certain embodiments, at least one instance of the first monomer is of Formula:
##STR00041##
or salt thereof, wherein
[0209] each instance of Z is independently C(R.sup.P).sub.2 or O;
[0210] each instance of R.sup.P is independently hydrogen, halogen, or substituted or unsubstituted, C.sub.1-10 alkyl;
[0211] each instance of is independently a single bond or double bond;
[0212] each instance of R.sup.H is independently hydrogen, halogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyi, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, OR.sup.a, OCN, OC(O)R.sup.a, OC(S)R.sup.a, OC(O)OR.sup.3, OC(O)N(R.sup.3).sub.2, OS(O)R.sup.a, OS(O)OR.sup.4, OC(O)N(R.sup.a).sub.2, OS(O).sub.2R.sup.a, OS(O).sub.2OR.sup.a, OS(O.sub.2N(R.sup.a).sub.2, OS(R.sup.a), OS(R.sup.a).sub.2(OR.sup.a), OS(R.sup.a((OR.sup.a).sub.2, OSi(OR.sup.a).sub.3), oxo, N(R.sup.a).sub.2, NC(R.sup.a).sub.2, NR.sup.a, NC, NCO, N.sub.3, NO.sub.2, NR.sup.aC(O)R.sup.a, NR.sup.aC(O)OR.sup.a, NR.sup.aC(O)N(R.sup.a).sub.2, NR.sup.aS(O)R.sup.a, NR.sup.aS(O)OR.sup.a, NR.sup.aS(O)N(R.sup.a).sub.2, NR.sup.aS(O).sub.2R.sup.a, NR.sup.aS(O).sub.2OR.sup.a, NR.sup.aS(O).sub.2N(R.sup.a).sub.2, SR.sup.a, S(O)R.sup.a, S(O)OR.sup.a, S(O)N(R.sup.a).sub.2, S(O).sub.2R.sup.a, S(O).sub.2OR.sup.a, S(O).sub.2N(R.sup.a).sub.2, SeR.sup.a, halogen, CN, C(NR.sup.a)R.sup.a, C(NR.sup.a)OR.sup.a, C(NR.sup.a)N(R.sup.a).sub.2, C(NR.sup.a)N(R.sup.a).sub.2, C(O)R.sup.a, C(O)OR.sup.a, C(O)SR.sup.2, C(S)OR.sup.2, or C(O)N(R.sup.3).sub.2,
[0213] or the two instances of R.sup.H of one or more instances of
##STR00042##
are joined with the intervening carbon atoms to independently form a substituted or unsubstituted, monocyclic carbocyclic ring, substituted or unsubstituted, monocyclic heterocyclic ring, substituted or unsubstituted, monocyclic aryl ring, or substituted or unsubstituted, monocyclic heteroaryl ring; and
[0214] each instance of R.sup.a is independently hydrogen, substituted or unsubstituted alkyl, substituted or unsubstituted alkenyl, substituted or unsubstituted alkynyl, substituted or unsubstituted, monocyclic carbocyclyl, substituted or unsubstituted, monocyclic heterocyclyl, substituted or unsubstituted, monocyclic aryl, substituted or unsubstituted, monocyclic heteroaryl, a nitrogen protecting group when attached to a nitrogen atom, an oxygen protecting group when attached to an oxygen atom, or a sulfur protecting group when attached to a sulfur atom, or two instances of R.sup.a are joined to form substituted or unsubstituted heterocyclyl or substituted or unsubstituted heteroaryl.
[0215] In certain embodiments, each instance of the first monomer is independently of Formula (D1) or (D2):
##STR00043##
or a salt thereof, wherein:
[0216] each instance of x is independently 0, 1, or 2; and
[0217] each instance of y is independently 0, 1, or 2.
[0218] In certain embodiments, at least one instance of Z is C(R.sup.P).sub.2. In certain embodiments, each instance of Z is C(R.sup.P).sub.2. In certain embodiments, at least one instance of Z is CH.sub.2. In certain embodiments, each instance of Z is CH.sub.2.
[0219] In certain embodiments, each instance of R.sup.P is hydrogen. In certain embodiments, at least one instance of R.sup.P is hydrogen. In certain embodiments, at least one instance of R.sup.P is halogen. In certain embodiments, at least one instance of R.sup.P is unsubstituted, C.sub.1-6 alkyl or C.sub.1-6 alkyl substituted with one or more halogen. In certain embodiments, at least one instance of R.sup.P is unsubstituted methyl.
[0220] In certain embodiments, at least one instance of R.sup.H is hydrogen. In certain embodiments, each instance of R.sup.H is hydrogen.
[0221] In certain embodiments, at least one instance of R.sup.H is substituted or unsubstituted alkyl (e.g., CF.sub.3). In certain embodiments, at least one instance of R.sup.H is CN. In certain embodiments, at least one instance of R.sup.H is C(O)OR.sup.a (e.g., C(P)OCH.sub.3). In certain embodiments, at least one instance of R.sup.H is C(O)R.sup.a. In certain embodiments, at least one instance of R.sup.H is C(O)N(R.sup.a).
[0222] In certain embodiments, each instance of the linear units is of the formula:
##STR00044##
[0223] In certain embodiments, each instance of the first monomer is of Formula (D1), or a salt thereof. In certain embodiments, each instance of the first monomer is of Formula (D1).
[0224] In certain embodiments, at least one instance of the first monomer is of the formula:
##STR00045##
[0225] In certain embodiments, each instance of the first monomer is of the formula:
##STR00046##
[0226] In certain embodiments, each instance of the first monomer is of the formula:
##STR00047##
[0227] In certain embodiments, the two instances of R.sup.H of one or more instances of
##STR00048##
are joined with the intervening carbon atoms to independently form a substituted or unsubstituted, monocyclic carbocyclic ring, or substituted or unsubstituted, monocyclic heterocyclic ring. In certain embodiments, the two instances of R.sup.H of one or more instances of
##STR00049##
are joined with the intervening carbon atoms to independently form a substituted or unsubstituted, monocyclic cycloalkenyl ring. In certain embodiments, the two instances of R.sup.H of one or more instances of
##STR00050##
are joined with the intervening carbon atoms to independently form a substituted or un substituted, monocyclic, saturated heterocyclic ring. In certain embodiments, at least one instance of the first monomer comprises a substituted or unsubstituted partially unsaturated monocyclic carbocyclic ring or a substituted or unsubstituted partially unsaturated monocyclic heterocyclic ring.
[0228] certain embodiments, each instance of the linear units is of the formula:
##STR00051##
[0229] In certain embodiments, each instance of the first monomer is of Formula (D2), or a salt thereof. In certain embodiments, each instance of the first monomer is of Formula (D2).
[0230] In certain embodiments, each instance of x is 0. In certain embodiments, each instance of x is 1. In certain embodiments, each instance of x is 2.
[0231] In certain embodiments, each instance of y is 1. In certain embodiments, each instance of y is 0. In certain embodiments, each instance of v is 2.
[0232] In certain embodiments, each instance of x is 1, and each instance of y is 1. In certain embodiments, each instance of x is 1, and each instance of y is 0. In certain embodiments, each instance of x is 0, and each instance of y is 1.
[0233] In certain embodiments, each instance of the first monomer is of the formula:
##STR00052##
In certain embodiments, each instance of the first monomer is of the formula:
##STR00053##
In certain embodiments, each instance of the first monomer is of the formula:
##STR00054##
[0234] In certain embodiments, at least one instance of the first monomer is of the formula:
##STR00055##
[0235] In certain embodiments, at least one instance of the first monomer is of the formula:
##STR00056##
or salt thereof.
[0236] In certain embodiments, the hydroxylated oligomer or hydroxylated polymer, hydroxylated polymer, or copolymer is crosslinked. In certain embodiments, the hydroxylated oligomer or hydroxylated polymer is crosslinked because it comprises one or more instances of the crosslinking units. In certain embodiments, the crosslinking degree is between 5% and 50%, inclusive, mole:mole. In certain embodiments, the crosslinking degree is between 5% and 10%, inclusive, mole:mole. In certain embodiments, the crosslinking degree is between 10% and 20%, inclusive, mole:mole. In certain embodiments, the crosslinking degree is between 20% and 30%, inclusive, mole:mole. In certain embodiments, the crosslinking degree is between 30% and 40%, inclusive, mole:mole. In certain embodiments, the crosslinking degree is between 40% and 5(1%, inclusive, mole:mole. In certain embodiments, the crosslinking degree is not greater than the concentration of all the instances of the second in onotner in the hydroxylated oligomer or hydroxylated polymer, hydroxylated polymer, or copolymer, mole:mole. In certain embodiments, the hydroxylated polymer is a thermosetting polymer. In certain embodiments, the hydroxylated polymer is a thermosetting polymer. In certain embodiments, the copolymer is a thermosetting polymer.
[0237] In certain embodiments, the aqueous solubility of the hydroxylated oligomer or hydroxylated polymer is between 0.1 and 0.3, between 0.3 and 1, between 1 and 3, between 3 and 10, between 10 and 30, or between 30 and 100, inclusive, g/L, at 1 atmosphere and 20 C. In certain embodiments, the aqueous solubility of the hydroxylated oligomer or hydroxylated polymer is between 1 and 10, inclusive, g/L, at 1 atmosphere and 20 C.
[0238] In certain embodiments, the aqueous solubility of the hydroxylated polymer is between and 0.3, between 0.3 and 1, between 1 and 3, between 3 and 10, between 10 and 30, or between 30 and 100, inclusive, g/L, at 1 atmosphere and 20 C. In certain embodiments, the aqueous solubility of the hydroxylated polymer is between 1 and 10, inclusive, g/L, at 1 atmosphere and 20 C.
[0239] In certain embodiments, the molar ratio of the one or more instances of the first monomer to the one or more instances of the second monomer is between 100:1 and 30:1, between 30:1 and 10:1, between 10:1 and 3:1, or between 3:1 and 1:1, inclusive. In certain embodiments, the molar ratio of the one or more instances of the first monomer to the one or more instances of the second monomer is between 12:1 and 1.3:1, inclusive. In certain embodiments, the molar ratio of the one or more instances of the first monomer to the one or more instances of the second monomer is between 8:1 and 2:1, inclusive. In certain embodiments, the molar ratio of the one or more instances of the first monomer to the one or more instances of the second monomer is between 30:1 and 3:1, inclusive. In certain embodiments, the molar ratio of the one or more instances of the first monomer to the one or more instances of the second monomer is between 20:1 and 5:1, inclusive. In certain embodiments, the molar ratio of the one or more instances of the first monomer to the one or more instances of the second monomer is between 60:1 and 6:1, inclusive. In certain embodiments, the molar ratio of the one or more instances of the first monomer to the one or more instances of the second monomer is between 40:1 and 10:1, inclusive. In certain embodiments, the molar ratio of the one or more instances of the first monomer to one or more instances of a second monomer is between 1:2 and 2:1, inclusive, 6:1 and 19:1, inclusive, or 5:1 and 35:1, inclusive. In certain embodiments, the molar ratio of the one or more instances of the first monomer to the one or more instances of the second monomer is between 1:2 and 2:1, inclusive. In certain embodiments, the molar ratio of the one or more instances of the first monomer to the one or more instances of the second monomer is between 1:10 and 10:1 (e.g., between 1:5 and 5:1), inclusive. In some embodiments, the molar ratio of the one or more instances of the first monomer to the one or more instances of the second monomer is between 1:35 and 35:1, inclusive. In some embodiments, the molar ratio of the one or more instances of the second monomer to the one or more instances of the first monomer is between 1:33 and 1:27, inclusive. In some embodiments, the molar ratio of the one or more instances of the second monomer to the one or more instances of the first monomer is between 1:17 and 1:11, inclusive, In some embodiments, the molar ratio of the one or more instances of the second monomer to the one or more instances of the first monomer is between 1:11 and 1:6, inclusive. In certain embodiments, the molar ratio of the one or more instances of the first monomer to the one or more instances of the second monomer is about 1:1.
[0240] In certain embodiments, the volume ratio of the one or more instances of the first monomer to the one or more instances of the second monomer is between 100:1 and 30:1, between 30:1 and 10:1, between 10:1 and 3:1, or between 3:1 and 1:1, inclusive. In certain embodiments, the volume ratio of the one or more instances of the first monomer to the one or more instances of the second monomer is between 12:1 and 1.3:1. inclusive. In certain embodiments, the volume ratio of the one or more instances of the first monomer to the one or more instances of the second monomer is between 8:1 and 2:1, inclusive. In certain embodiments, the volume ratio of the one or more instances of the first monomer to the one or more instances of the second monomer is between 30:1 and 3:1, inclusive. In certain embodiments, the volume ratio of the one or more instances of the first monomer to the one or more instances of the second monomer is between 20:1 and 5:1, inclusive. In certain embodiments, the volume ratio of the one or more instances of the first monomer to the one or more instances of the second monomer is between 60:1 and 6:1, inclusive. In certain embodiments, the volume ratio of the one or more instances of the first monomer to the one or more instances of the second monomer is between 40:1 and 10:1, inclusive.
[0241] In certain embodiments, the average molecular weight of the hydroxylated. oligomer or hydroxylated polymer is between 300 Da and 1 kDa, between 1 kDa and 3 kDa, between 3 kDa and 10 kDa, between 10 kDa and 100 kDa, or between 100 kDa and 1,000 kDa, inclusive. In certain embodiments, the average molecular weight of the hydroxylated oligomer or hydroxylated polymer is between 1 kDa and 10 kDa, inclusive. In certain embodiments, the average molecular weight is as determined by gel permeation chromatography, in certain embodiments, the average molecular weight of the hydroxylated oligomer car hydroxylated polymer as determined by gel permeation chromatography is between 300 Da and 1,000 kDa, inclusive. in certain embodiments, the average molecular weight of the hydroxylated oligomer or hydroxylated polymer as determined by get permeation chromatography is between 1 kDa. and 8 kDa, inclusive.
[0242] In certain embodiments, the average molecular weight of the hydroxylated polymer is between 300 Da and 1 kDa, between 1 kDa, and 3 kDa, between 3 kDa. and 10 kDa, between 10 kDa and 100 kDa, or between 100 kDa and 1,000 kDa., inclusive. In certain embodiments, the average molecular weight of the hydroxylated polymer is between 1 kDa and 10 kDa, inclusive.
[0243] In certain embodiments, the average molecular weight is as determined by gel permeation chromatography. In certain embodiments, the average molecular weight of the hydroxylated polymer as determined by gel permeation chromatography is between 300 Da and 1,000 kDa, inclusive. In certain embodiments, the average molecular weight of the hydroxylated polymer as determined by gel permeation chromatography is between 1 kDa and 8 kDa, inclusive.
[0244] In certain embodiments, the average molecular weight of the copolymer is between 10 kDa and 10,000 kDa, inclusive. In certain embodiments, the average molecular weight of the copolymer is between 10 kDa, and 30 kDa, between 30 kDa, and 100 kDa, between 100 kDa and 1,000 kDa, between 1,000 kDa and 10,000 kDa, or between 10,000 kDa and 100,000 kDa, inclusive. In certain embodiments, the average molecular weight of the copolymer is between 10 kDa and 100 kDa, inclusive. In certain embodiments, the average molecular weight is as determined by gel permeation chromatography. In certain embodiments, the average molecular weight of the copolymer as determined by gel permeation chromatography is between 10 kDa, and 100,000 kDa, inclusive. In certain embodiments, the number average polymerization degree is between 2 and 1,000, inclusive, with respect to the first monomer; and between 2 and 1,000, inclusive, with respect to the second monomer. In certain embodiments, the number average polymerization degree is between 10 and 200, inclusive, with respect to the first monomer; and between 10 and 200, inclusive, with respect to the second monomer. In certain embodiments, the number average polymerization degree is between 15 and 100, inclusive, with respect to the first monomer; and between 15 and 100, inclusive, with respect to the second monomer. In certain embodiments, the number average polymerization degree is between 2 and 1,000, between 10 and 1,000, between 100 and 1,000, between 2 and 100, between 10 and 100, between 2 and 10, inclusive, with respect to the first monomer. In certain embodiments, the number average polymerization degree is between 2 and 1,000, between 10 and 1,000, between 100 and 1,000, between 2 and 100, between 10 and 100, between 2 and 10, inclusive, with respect to the second, monomer.
[0245] In certain embodiments, the dispersity (I)) of the copolymer is between 1 and 2, between 1.1 and 2, between 1.3 and 2, between 1.5 and 2, between 1.1 and 1.5. between 1.1 and 1.3, between 1.3 and 2, between 1.3 and 1.5, between 1.5 and 2, inclusive.
[0246] In certain embodiments, the average hydrodynamic diameter of the hydroxylated oligomer or hydroxylated polymer is between 1 and 100 nm, inclusive. In certain embodiments, the average hydrodynamic diameter of the hydroxylated oligomer or hydroxylated polymer is between 1 and 10 nm, inclusive. In certain embodiments, the average hydrodynamic diameter of the hydroxylated oligomer or hydroxylated polymer is between 10 and 30 nm, inclusive. In certain embodiments, the average hydrodynamic diameter of the hydroxylated oligomer or hydroxylated polymer is between 30 and 100 nm, inclusive. In certain embodiments, the average hydrodynamic diameter of the hydroxylated polymer is between 1 and 100 nm, inclusive. In certain embodiments, the average hydrodynamic diameter of the hydroxylated polymer is between 1 and 10 nm, inclusive. In certain embodiments, the average hydrodynamic diameter of the hydroxylated polymer is between 10 and 30 nm, inclusive. In certain embodiments, the average hydrodynamic diameter of the hydroxylated polymer is between 30 and 100 nm, inclusive. In certain embodiments, the average hydrodynamic diameter is as determined by diffusion ordered spectroscopy (DOSY).
[0247] In certain embodiments, the copolymer is a block copolymer, preferably a block polymer comprising at least four consecutive blocks, wherein:
[0248] each of the first consecutive block and the third consecutive block independently comprises one or more repeating units formed from the first monomer or the third monomer if present; and
[0249] each of the second consecutive block and the fourth consecutive block independently comprises one or more repeating units formed from the second monomer.
[0250] In certain embodiments, the copolymer is a random copolymer.
[0251] In certain embodiments, the step of polymerizing is substantially free (e.g., between 90%-99% free) of a chain transfer agent.
[0252] In certain embodiments, the step of hydrolyzing the copolymer comprises hydrolyzing at least 50% of the OSi bonds of the copolymer to form OH. In certain embodiments, the step of hydrolyzing the copolymer comprises hydrolyzing between 50% and 70%, inclusive, of the OSi bonds of the copolymer to form OH. In certain embodiments, the step of hydrolyzing the copolymer comprises hydrolyzing between 70% and 90%, inclusive, of the OSi bonds of the copolymer to form OH. In certain embodiments, the step of hydrolyzing the copolymer comprises hydrolyzing between 90% and 99%, inclusive, of the OSi bonds of the copolymer to form OH. In certain embodiments, the step of hydrolyzing the copolymer comprises hydrolyzing at least 95% of the OSi bonds of the copolymer to form OH.
[0253] In certain embodiments, the step of hydrolyzing the copolymer comprises ambient temperature, ambient pressure, and a reaction time of between 1 hour and 48 hours (e.g., between 1 hour and 6 hours, between 6 hour and 24 hours, between 24 hour and 48 hours), inclusive.
[0254] In certain embodiments, the step of hydrolyzing the copolymer comprises reacting the copolymer with a fluoride source. In certain embodiments, the fluoride source is tetra(unsubstitutedalkyl)-ammonium fluoride. In certain embodiments, the fluoride source is tetra(unsubstituted C.sub.1-6 alkyl)-ammonium fluoride (e.g., TBAF). In certain embodiments, the fluoride source is a metal fluoride (e.g., alkali metal fluoride or alkaline earth metal fluoride). In certain embodiments, a polymer is chemically degradable in the presence of tetra-n-butylammonium fluoride (TBAF). In certain embodiments, the fluoride source is an acidic fluoride source (e.g., HF). In certain embodiments, the fluoride source is a latent fluoride source (e.g., tris(dimethylamino)suffonium difluorotrimethyl silicate (TASF)).
[0255] In some embodiments, the amount of the fluoride source is about 1 equivalent (mole:mole) relative to the amount of the second monomer. In some embodiments, the amount of the fluoride source is in excess (e.g., about 2 equivalents) relative to the amount of the second monomer. In certain embodiments, the step of hydrolyzing the copolymer comprises reacting the copolymer with an acid.
[0256] In certain embodiments, the acid is an aqueous solution of an acid. In certain embodiments, the acid is an inorganic acid. In certain embodiments, the acid is an organic acid. In certain embodiments, the acid has a pK.sub.a value of less than 3, less than 2, less than 1, or less than 0, under ambient conditions, in certain embodiments, the acid is HCl, HBr, HI, HClO.sub.4, HNO.sub.3, H.sub.2SO.sub.4, CH.sub.3SO.sub.3H, or CF.sub.3SO.sub.3H. In certain embodiments, the acid is HCl. In certain embodiments, the acid is CF.sub.3CO.sub.2H.
[0257] In some embodiments, the amount of the acid is about 1 equivalent (mole:mole) relative to the amount of the second monomer. In some embodiments, the amount of the acid is in excess (e.g., about 2 equivalents) relative to the amount of the second monomer.
[0258] In another aspect, the present disclosure provides conjugates (conjugates of the present disclosure) prepared by reacting a hydroxy-reacting substance with a hydroxylated oligomer or hydroxylated polymer of the present disclosure, wherein hydroxy-reacting substance comprises at least one instance of a hydroxy-reacting moiety.
[0259] In another aspect, the present disclosure provides methods of preparing a conjugate comprising reacting a hydroxy-reacting substance with a hydroxylated oligomer or hydroxylated polymer of the present disclosure.
[0260] In certain embodiments, the hydroxy-reacting substance is a hydroxy-reacting small molecule. In certain embodiments, the hydroxy-reacting substance is a carboxylic acid, a carboxylic halide, a carboxylic anhydride, a sulfonic acid, a sulfonyl halide, a sulfonic anhydride, a sulfinic acid, a sulfinyl halide, or a sulfinic anhydride. In certain embodiments, the hydroxy-reacting substance is lactide. In certain embodiments, the hydroxy-reacting substance is a hydroxy-reacting polymer. In certain embodiments, the average molecular weight of the hydroxy-reacting polymer is between 1 kDa and 3 kDa, between 3 kDa and 10 kDa, between 10 kDa and 30 kDa, between 30 kDa and 100 kDa, or between 100 kDa and 1,000 kDa, inclusive. In certain embodiments, the average molecular weight of the hydroxy-reacting polymer is between 3 kDa and 30 kDa, inclusive, In certain embodiments. the average molecular weight is as determined by gel permeation chromatography. in certain embodiments, the average molecular weight of the hydroxy-reacting polymer as determined by gel permeation chromatography is between 1 kDa and 1,000 kDa, inclusive.
[0261] In certain embodiments, the hydroxy-reacting substance is a polysiloxane, wherein the polysiloxane comprises at least one instance of a hydroxy-reacting moiety. In certain embodiments, the hydroxy-reacting substance is a polydimethylsiloxane (PDMS), wherein the PDMS comprises at least one instance of a hydroxy-reacting moiety (e.g., hydride (e.g., Si(IV-H)).
[0262] In certain embodiments, at least one instance of the hydroxy-reacting moiety is Si(IV)-H, Si(IV)-(a leaving group), C(IV)-(a leaving group), C(O)OH, C(O)-(a leaving group), C(O)O, C(O)OC(O), S)O)OH, S(O)-(a leaving group), S(O.sub.2OH, S(O).sub.2-(a leaving group, OH, or O-(a leaving grouip). In certain embodiments, at least one instance of the hydroxy-reacting moiety is Si(IV)-H. In certain embodiments, at least one instance of the hydroxy-reacting moiety is C(O)-(a leaving group). In certain embodiments, at least one instance of the hydroxy-reacting moiety is O-(a leaving group).
[0263] In certain embodiments, the hydroxy-reacting substance is a polylactic acid (PLA). in certain embodiments, the hydroxy-reacting substance is a polyethylene glycol (PEG). In certain embodiments, the hydroxy-reacting substance is a PEG, wherein the average molecular weight of the PEG as determined by gel permeation chromatography is between 300 Da and I kDa., between 1 kDa and 3 kDa, between 3 kDa and 10 kDa, between 10 kDa and 30 kDa, between 30 kDa and 100 kDa, or between 100 kDa and 1,000 kDa, inclusive.
[0264] In another aspect, the present disclosure provides compositions (compositions of the present disclosure) comprising:
[0265] a compound, copolymer, hydroxylated oligomer, hydroxylated polymer, or conjugate of the present disclosure; and
[0266] optionally an excipient.
[0267] In certain embodiments, the composition of the present disclosure is a pharmaceutical composition. In certain embodiments, the composition of the present disclosure further comprises excipient. In certain embodiments, the pharmaceutical composition of the present disclosure further comprises a pharmaceutically acceptable excipient.
[0268] Compositions described herein can be prepared by any method known in the art. In general, such preparatory methods include bringing the hydroxylated polymer into association with an excipient, and/or one or more other accessory ingredients, and then, if necessary and/or desirable, shaping, and/or packaging the product into a desired unit.
[0269] In another aspect, the present disclosure provides kits comprising:
[0270] a compound, copolymer, hydroxylated oligomer, hydroxylated polymer, or conjugate of the present disclosure; and
[0271] instructions for using the compound, copolymer, hydroxylated oligomer, hydroxylated polymer, or conjugate.
[0272] Kits may be commercial packs or reagent packs. The kits may further comprise a container (e.g., a vial, ampule, bottle, syringe, and/or dispenser package, or other suitable container). In certain embodiments, a kit further comprises instructions for using the compound. In certain embodiments, a kit further comprises instructions for using the copolymer. In certain embodiments, a kit further comprises instructions for using the hydroxylated polymer (e.g., for preparing a conjugate). In certain embodiments, a kit further comprises instructions for using the conjugate. The details of certain embodiments of the invention are set forth in the present section.
[0273] Other features, objects, and advantages of the invention will be apparent from the Definitions, Figures, Examples, and Claims. The aspects described herein are not limited to specific embodiments, methods, apparati, or configurations, and as such can, of course, vary. The terminology used herein is for the purpose of describing particular aspects only and, unless specifically defined herein, is not intended to be limiting.
EXANIPLES
[0274] In order that the invention described herein may be more fully understood, the following examples are set forth. The synthetic and biological examples described herein are offered to illustrate the present disclosure and are not to be construed in any way as limiting their scope.
Example 1
[0275] 2.64 g of cis-butene diol (30 mmol) was dissolved in 1.5 L of dichloromethane. Next, 4.08 g of imidazole (60 mmol) was added. Finally, 30 mmol of dichlorosilane ((5-bicyclo[2.2.1]hept-2-enyl)methyldichlorosilane or [(5-bicyclo[2.2.1]hept-2-enypethyl]methyldichlorosilane) in 100 mL of DOA was added dropwise over 1 hour. A significant quantity of white precipitate formed. The solution was then filtered through a 222 in. pad of silica and concentrated to yield the corresponding XL monomer compounds as clear oils. The XI monomer prepared from 5-bicyclo[2.2.1]hept-2-enypmethyldichlorosilane was XLSi7. The XL monomer prepared from [(5-bicyclo[2.2,1]hept-2-enyl)ethyl]methyldichlorosilane was XISi7-2. Exemplary results are shown in
Example 2
[0276] 100 L of XL monomer was added to a 1 mL vial, followed by 900 L of DCPD and mixed thoroughly by vortex. Separately, 2.0 mg of finely powdered Grubbs 2nd generation catalyst were weighed into a 1 mL vial. The DCPD/XL monomer mixture was added to the catalyst, vortexed until complete dissolution, and transferred in 150 L aliquots to 1 mL vials. The samples were immediately cured at 120 C. for 30 minutes, then cooled to room temperature and removed form the vials with a hammer. The resulting copolymer was DCPD-XLSi7 or DCPD-XLSi7-2.
[0277] Samples were then placed in 5 mL of 0.2M tetrabutylammonium fluoride in THF, and heated to 50 C. on a hot plate overnight, resulting in full degradation of solids. Final solid pieces were removed from solution, and the solution was concentrated under vacuum to 1 mL, then slowly dropped into 100 mL acetone under rapid stirring. The resulting precipitate was filtered off, dissolved in CDCl3 and NMR spectra were taken. Exemplary results are shown in
Example 3
[0278] 100 L of XL monomer was added to a 1 mL vial, followed by 900 L of DCPD and mixed thoroughly by vortex. Separately, 2.0 mg of finely powdered Grubbs 2nd generation catalyst were weighed into a 1 mL vial. The DCPD/XL monomer mixture was added to the catalyst, vortexed until complete dissolution, and transferred in 300 L aliquots to rectangular silicon molds. The samples were immediately cured in the molds at 120 C. for 30 minutes, then cooled to room temperature and removed from the molds. The resulting copolymer was DCPD-XLSi7.
[0279] The samples were sanded down to have cross-sectional dimensions 2.53.0 mm, and 0 were analyzed by dynamic mechanical analysis in triplicate, in tensile mode using a TA Instruments DMAQ800. Samples were measured using 125% force tracking, 0.1N preload force and 10 m amplitude strain at 1 Hz, from room temperature to 220 C. at a heating rate of 3 C. min .sup.1. Exemplary results are shown in
Example 4
[0280] 2.72 g of imidazole was dissolved in 1 L of dry DCM. To this solution was added 2.02 g of (Z)-pent-2-ene-1,5-diol and 1.69 g of SiCl.sub.4, each dissolved in DCII to a final volume of 24 mL, over the course of two hours with a syringe pump. The resulting cloudy mixture was then filtered through a 222 in. plug of silica and concentrated to yield 150 mg of SpiroSi as a moisture-sensitive clear oil.
Example 5
[0281] 900 L of DCPD was added to 100 L of SpiroSi. The mixture was added to a vial containing 2 mg/mL of finely powdered Grubbs' 2nd generation catalyst The resulting mixture was added as 200 mg portions into glass vials, and heated at 120 C. for 30 minutes to cure. The vials were then broken to release the samples. Those samples were 10% v/v samples of SpiroSi-doped pDCPD.
[0282] An analogous protocol using 950 L of DCPD and 50 L of SpiroSi was used to synthesize 5% v/v samples of SpiroSi-doped pDCPD.
[0283] A sample was incubated with 5 mL of 0.2 M TBAF in THY for 24 hours. The soluble fragments were carefully removed by pipette and the residual solids were resuspended in fresh THF. The fragments were redissolved in chloroform, concentrated, and characterized by NMR. Exemplary results are shown in
Example 6
[0284] 0.880 g of cis-butane-diol and 1.36 g of imidazole were dissolved in 1 L of dry DCM. Next, (5-bicycle[2.2.1]hept-2-enyl)methyldichlorosilane in 100 mL of DCM was added dropwise over 1 hour. The solution was then filtered through a 222 plug of silica and concentrated to yield 0.95 g of NbMeSi as a clear oil. Exemplary NMR results are shown in
Examples 7
[0285] 1 mL of monomer solution was added to a vial containing 2 mg/mL of finely powdered Grubbs' 2nd generation catalyst. The resulting mixture was added into a silicone mold (approximately 300 L per mold). The samples were heated at 120 C. for 30 minutes, then taken out of the oven and cut out of the mold. The samples were further sanded before measurement by Dynamic Mechanical Analysis (DMA).
[0286] DMA was conducted in tensile mode using a TA Instruments Q800. Temperature sweeps were conducted using 10 m fixed amplitude, 0.01N preload force and 125.0% force tracking, with a frequency of 1 Hz and a heating rate of 3 degrees Celsius per minute, from room temperature to 220 Celsius.
EQUIVALENTS AND SCOPE
[0287] In the claims articles such as a, an, and the may mean one or more than one unless indicated to the contrary or otherwise evident from the context. Claims or descriptions that include or between one or more members of a group are considered satisfied if one, more than one, or all of the group members are present in, employed in, or otherwise relevant to a given product or process unless indicated to the contrary or otherwise evident from the context, The invention includes embodiments in which exactly one member of the group is present in, employed in, or otherwise relevant to a given product or process. The invention includes embodiments in which more than one, or all of the group members are present in, employed in, or otherwise relevant to a given product or process.
[0288] Furthermore, the invention encompasses all variations, combinations, and permutations in which one or more limitations, elements, clauses, and descriptive terms from one or more of the listed claims is introduced into another claim. For example, any claim that is dependent on another claim can be modified to include one or more limitations found in any other claim that is dependent on the same base claim. Where elements are presented as lists, e.g, in Markush group format, each subgroup of the elements is also disclosed, and any element(s) can be removed from the group. It should it be understood that, in general, where the invention, or aspects of the invention, is,/are referred to as comprising particular elements and/or features, certain embodiments of the invention or aspects of the invention consist, or consist essentially of, such elements and/or features. For purposes of simplicity, those embodiments have not been specifically set forth in hoer: verha herein. It is also noted that the terms comprising, including, and containing, and all other tenses thereof, are intended to be open and permits the inclusion of additional possibilities (e4;., elements or steps). Where ranges are given, endpoints are included. Furthermore, unless otherwise indicated or otherwise evident from the context and understanding of one of ordinary skill in the art, values that are expressed as ranges can assume any specific value or sub-range within the stated ranges in different embodiments of the invention, to the tenth of the unit of the lower limit of the range, unless the context clearly dictates otherwise.
[0289] This application refers to various issued patents, published patent applications, journal articles, and other publications, all of which are incorporated herein by reference. If there is a conflict between any of the incorporated references and the instant specification, the specification shall control. In addition, any particular embodiment of the present invention that falls within the prior art may be explicitly excluded from any one or more of the claims. Because such embodiments are deemed to be known to one of ordinary skill in the art, they may be excluded even if the exclusion is not set forth explicitly herein. Any particular embodiment of the invention can be excluded from any claim, for any reason, whether or not related to the existence of prior art.
[0290] Those skilled in the art will recognize or be able to ascertain using no more than routine experimentation many equivalents to the specific embodiments described herein. The scope of the present embodiments described herein is not intended to be limited to the above Description, but rather is as set forth in the appended claims. Those of ordinary skill in the art will appreciate that various changes and modifications to this description may be made without departing from the spirit or scope of the present invention, as defined in the following claims.