Chiral platinum complex, method for preparing the same, and method for using the same

Abstract

A chiral platinum complex having a chemical formula (I): ##STR00001##
A method for synthesizing the chiral platinum complex (I), includes: dissolving 0.700 g of Pt(DMSO).sub.2(NO.sub.3).sub.2 in 30 mL of dichloromethane as a solvent to yield a solution; adding 0.450 g of 1,4-(4R)-diphenyl-2-oxazolinyl benzene to the solution, and reflux a resulting mixture for reaction for 48 hrs, and stopping the reaction; filtrating reaction products; and adding dichloromethane and petroleum ether, and naturally volatilizing to yield a binuclear platinum complex single crystal. A method for condensation of benzophenone imine and trimethylsilitrile by using the chiral platinum complex as a catalyst. A method for treating cancer includes administering the chiral platinum complex to a patient in need thereof. The cancer includes: lung cancer (A549), nasopharyngeal carcinoma (KB), anti-drug-resistant nasopharyngeal carcinoma (KB-VIn), and human breast cancer (MCF-7).

Claims

1. A method for condensation of benzophenone imine and trimethylsilitrile comprising using the chiral platinum complex having a chemical formula (I): ##STR00005##

Description

BRIEF DESCRIPTION OF THE DRAWINGS

(1) FIG. 1 is an X-ray diffraction analysis drawing of binuclear platinum complex crystal;

(2) FIG. 2 is a NMR spectrogram of binuclear platinum complex crystal;

(3) FIG. 3 is a nuclear magnetic carbon spectrum of binuclear platinum complex crystal.

DETAILED DESCRIPTION OF THE EMBODIMENTS

(4) 1. Platinum Bichloride and Dimethyl Sulfoxide Complex

(5) 1.2042 g of platinum bichloride, 10 mL of DMSO, and 30 mL of dichloromethane were added to a 100 mL two-mouth flask to yield a mixture. The mixture was refluxed for 60 hrs, the reaction was stopped, and a resulting reaction mixture was stood. A solid dimethyl sulfoxide platinum complex was obtained with a yield thereof being 45%.

(6) Elemental analysis results were as follows:

(7) Test values: C: 11.78%, H: 2.91%;

(8) Calculated values: C: 11.38%, H: 2.86%, IR (KBr): 1157, 1134, 450, 430.

(9) 2. Dimethyl Sulfoxide and Platinum Nitrate Complex

(10) To a two-mouth flask, 0.3521 g of dimethyl sulfoxide platinum chloride, 0.5135 g of silver nitrate, and 20 mL of dichloromethane as solvent, were added for carrying out reaction in dark by using an aluminum foil at room temperature for 30 hrs. A resulting reaction mixture was filtrated and added with dichloromethane/trichloromethane in a volume ratio of 1/1 to prepare a solution. The resulting solution was naturally volatilized to obtain a dimethyl sulfoxide platinum nitrate complex in a solid form, with a yield thereof being 42%.

(11) 3. Preparation of Dimethyl Sulfoxide Binuclear Platinum Complex Crystal

(12) 0.700 g of Pt(DMSO).sub.2(NO.sub.3).sub.2 were taken and dissolved with 30 mL of dichloromethane as the solvent to yield a resulting solution. 0.450 g of 1,4-(4R)-diphenyl-2-oxazolinyl benzene was added to the resulting solution for reflux reaction for 48 hrs. The reaction was stopped. Thereafter, reaction products were filtrated, and added with dichloromethane and petroleum ether, and naturally volatilized, to obtain a new single crystal of binuclear platinum complex, with a yield thereof being 90%, m.p. 121-122° C.; [α]5D=+125.0° (c 0.04, DMF). Elemental analysis: C156H144N24048Pt6: Test values: C, 43.90, H, 3.71, N, 7.51; Calculated values: (%) C, 43.64, H, 3.38, N, 7.83; .sup.1H NMR (600 MHz, DMSO), δ ppm 7.95 (s, 8H, ArH), 7.12-7.32 (m, 20H, ArH), 4.56-4.64 (m, 4H, CH), 4.45-4.49 (m, 4H, CH), 4.16 (t, J=7.9 Hz, 4H, CH), 3.04 and 3.02 (dd, J=6.1, 6.8 Hz, 4H, 2×CH2), 2.85 and 2.82 (dd, J=7.3, 7.3 Hz, 4H, 2×CH2); 13C NMR (150 MHz, DMSO) 162.7, 138.5, 130.4, 129.8, 128.8, 128.6, 126.8, 72.3, 67.8, 41.3; ν.sub.max (cm.sup.−1) 3448, 3026, 2924, 2854, 2426, 1645, 1610, 1571, 1510, 1497, 1454, 1384, 1281, 1259, 1084, 1063, 1015, 967, 919, 861, 839, 756, 728, 699;

(13) The data of the complex crystal are as follows:

(14) Empirical formula: C156H144N24O48Pt6

(15) Molecular weight: 4293.49

(16) Temperature: 293.19(10)K

(17) Wavelength: 1.54184 Å

(18) Crystal system, spatial group: Monoclinic system, C2

(19) crystal cell parameters: a=33.373 Å; α=90°.

(20) b=9.580(3) Å; β=118.303(6°).

(21) c=32.316 (9) Å; γ=90°.

(22) Volume: 9096 (4) Å {circumflex over ( )}3

(23) Electric density: 2, 1.380 Mg/m{circumflex over ( )}3

(24) Absorption, correction parameter: 4.696 mm{circumflex over ( )}−1

(25) Number of electrons in a single cell: 3682.0.0

(26) Crystal size: 0.20×0.12×0.06 mm

(27) Theta angle range: 4.472 to 50

(28) Index collection range of HKL: −39<=h<=39, −11<k<11, −38<l<=38

(29) Collect/Independent diffraction data: 16001/4652[R(int)=0.0752]

(30) Method of absorption correction: Multilayer scanning

(31) Method used for refinement: Least square method of matrix of F{circumflex over ( )}2

(32) Number of data/number of use limit/number of parameters: 4652/499/803

(33) Method used for refinement: 0.995

(34) Coincidence factor for diffraction point: R1=0.0902, ωR2=0.2485

(35) Coincidence factor of observable diffraction: R1=0.1416, ωR2=0.2892

(36) Maximum peak and valley on the difference Fourier diagram: 1.00 and −2892 e.Math.Å{circumflex over ( )}−3

(37) Typical Bond Length Data for Crystal are Listed as Follows:

(38) TABLE-US-00001 Atom Atom Length/Å C.sub.1 C.sub.4 1.42(3) C.sub.1 N.sub.1 1.36(3) C.sub.1 O.sub.1 1.30(2) C.sub.2 C.sub.3 1.58(3) C.sub.2 O.sub.1 1.37(3) C.sub.3 C.sub.20 1.56(3) C.sub.3 N.sub.1 1.53(2) C.sub.4 C.sub.5 1.42(3) C.sub.4 C.sub.9 1.34(3) C.sub.5 C.sub.6 1.29(3) C.sub.6 C.sub.7 1.51(3) C.sub.7 C.sub.8 1.20(3) C.sub.7 C.sub.10 1.49(3) C.sub.8 C.sub.9 1.51(3) C.sub.10 N.sub.3 1.29(3) C.sub.10 O.sub.3 1.33(2) C.sub.11 C.sub.12 1.61(2) C.sub.11 O.sub.3 1.55(2) C.sub.12 C.sub.13 1.39(3) C.sub.12 N.sub.3 1.48(2) C.sub.13 C.sub.14 1.47(2) C.sub.14 C.sub.15 1.3900 C.sub.14 C.sub.19 1.3900 C.sub.15 C.sub.16 1.3900 C.sub.16 C.sub.17 1.3900 C.sub.17 C.sub.18 1.3900 C.sub.18 C.sub.19 1.3900 C.sub.20 C.sub.21 1.53(2) C.sub.21 C.sub.22 1.3900 C.sub.21 C.sub.26 1.3900 C.sub.22 C.sub.23 1.3900 C.sub.23 C.sub.24 1.3900 C.sub.24 C.sub.25 1.3900 C.sub.25 C.sub.26 1.3900 C.sub.27 C.sub.28 1.46(3) C.sub.27 C.sub.46 1.53(3) C.sub.27 N.sub.2 1.47(3) C.sub.28 O.sub.2 1.38(3) C.sub.29 C.sub.30 1.40(3) C.sub.29 N.sub.2 1.36(3) C.sub.29 O.sub.2 1.34(2) C.sub.30 C.sub.31 1.37(3) C.sub.30 C.sub.35 1.46(3) C.sub.31 C.sub.32 1.46(3) C.sub.32 C.sub.33 1.41(3) C.sub.33 C.sub.34 1.37(3) C.sub.33 C.sub.36 1.53(3) C.sub.34 C.sub.35 1.25(3) C.sub.36 N.sub.4 1.29(3) C.sub.36 O.sub.4 1.26(3) C.sub.37 C.sub.38 1.47(3) C.sub.37 O.sub.4 1.35(2) C.sub.38 C.sub.39 1.66(3) C.sub.38 N.sub.4 1.43(3) C.sub.39 C.sub.40 1.59(2) C.sub.40 C.sub.41 1.3900 C.sub.40 C.sub.45 1.3900 C.sub.41 C.sub.42 1.3900 C.sub.42 C.sub.43 1.3900 C.sub.43 C.sub.44 1.3900 C.sub.44 C.sub.45 1.3900 C.sub.46 C.sub.47 1.49(2) C.sub.47 C.sub.48 1.3900 C.sub.47 C.sub.52 1.3900 C.sub.48 C.sub.49 1.3900 C.sub.49 C.sub.50 1.3900 C.sub.50 C.sub.51 1.3900 C.sub.51 C.sub.52 1.3900 N.sub.1 Pt.sub.1 2.141(18) N.sub.2 Pt.sub.1 2.025(14) N.sub.3 Pt.sub.2 2.080(16) N.sub.4 Pt.sub.2 2.152(13) C.sub.53 C.sub.67.sup.1 1.44(8) C.sub.53 N.sub.5 1.19(4) C.sub.53 O.sub.5 1.42(4) C.sub.54 C.sub.55 1.73(5) C.sub.54 O.sub.5 1.38(5) C.sub.55 C.sub.56 1.61(3) C.sub.55 N.sub.5 1.45(4) C.sub.56 C.sub.57 1.32(3) C.sub.57 C.sub.58 1.3900 C.sub.57 C.sub.62 1.3900 C.sub.58 C.sub.59 1.3900 C.sub.59 C.sub.60 1.3900 C.sub.60 C.sub.61 1.3900 C.sub.61 C.sub.62 1.3900 C.sub.63 C.sub.64 1.60(3) C.sub.63 N.sub.6 1.36(4) C.sub.63 O.sub.6 1.43(4) C.sub.64 C.sub.65 1.3900 C.sub.64 C.sub.69 1.3900 C.sub.65 C.sub.66 1.3900 C.sub.66 C.sub.67 1.3900 C.sub.67 C.sub.53.sup.1 1.44(4) C.sub.67 C.sub.68 1.3900 C.sub.68 C.sub.69 1.3900 C.sub.70 C.sub.71 1.51(3) C.sub.70 O.sub.6 1.42(2) C.sub.71 C.sub.72 1.38(4) C.sub.71 N.sub.6 1.45(4) C.sub.72 C.sub.73 1.36(4) C.sub.73 C.sub.74 1.3900 C.sub.73 C.sub.78 1.3900 C.sub.74 C.sub.75 1.3900 C.sub.75 C.sub.76 1.3900 C.sub.76 C.sub.77 1.3900 C.sub.77 C.sub.78 1.3900 N.sub.5 Pt.sub.3 1.99(3) N.sub.6 Pt.sub.3 2.09(2) N.sub.7 O.sub.7 1.09(3) N.sub.7 O.sub.8 1.24(3) N.sub.7 O.sub.9 1.29(3) .sup.1−X, +Y, −Z

(39) Typical bond angle data for crystal are listed as follows:

(40) TABLE-US-00002 Atom Atom Atom Angle/° Atom Atom Atom Angle/° N.sub.1 C.sub.1 C.sub.4 126.5(18) C.sub.52 C.sub.47 C.sub.46 118.1(12) O.sub.1 C.sub.1 C.sub.4 121.9(17) C.sub.47 C.sub.48 C.sub.49 120.0 O.sub.1 C.sub.1 N.sub.1 111.6(17) C.sub.50 C.sub.49 C.sub.48 120.0 O.sub.1 C.sub.2 C.sub.3 104.6(17) C.sub.49 C.sub.50 C.sub.51 120.0 C.sub.20 C.sub.3 C.sub.2 108.5(19) C.sub.52 C.sub.51 C.sub.50 120.0 N.sub.1 C.sub.3 C.sub.2 100.0(17) C.sub.51 C.sub.52 C.sub.47 120.0 N.sub.1 C.sub.3 C.sub.20 106.5(14) C.sub.1 N.sub.1 C.sub.3 108.4(16) C.sub.1 C.sub.4 C.sub.5 116.8(17) C.sub.1 N.sub.1 Pt.sub.1 126.7(13) C.sub.9 C.sub.4 C.sub.1 120.8(19) C.sub.3 N.sub.1 Pt.sub.1 124.9(13) C.sub.9 C.sub.4 C.sub.5 122.2(19) C.sub.27 N.sub.2 Pt.sub.1 128.5(13) C.sub.6 C.sub.5 C.sub.4 121.1(19) C.sub.29 N.sub.2 C.sub.27 102.2(16) C.sub.5 C.sub.6 C.sub.7 118(2) C.sub.29 N.sub.2 Pt.sub.1 128.8(13) C.sub.8 C.sub.7 C.sub.6 119.8(18) C.sub.10 N.sub.3 C.sub.12 109.5(15) C.sub.8 C.sub.7 C.sub.10 122.6(17) C.sub.10 N.sub.3 Pt.sub.2 126.9(11) C.sub.10 C.sub.7 C.sub.6 117.6(16) C.sub.12 N.sub.3 Pt.sub.2 123.1(11) C.sub.7 C.sub.8 C.sub.9 124.3(19) C.sub.36 N.sub.4 C.sub.38 102.6(16) C.sub.4 C.sub.9 C.sub.8 114.0(19) C.sub.36 N.sub.4 Pt.sub.2 130.1(14) N.sub.3 C.sub.10 C.sub.7 127.9(15) C.sub.38 N.sub.4 Pt.sub.2 127.3(12) N.sub.3 C.sub.10 O.sub.3 119.3(16) C.sub.1 O.sub.1 C.sub.2 O.sub.3 C.sub.10 C.sub.7 112.8(17) C.sub.29 O.sub.2 C.sub.28 O.sub.3 C.sub.11 C.sub.12 101.6(12) C.sub.10 O.sub.3 C.sub.11 C.sub.13 C.sub.12 C.sub.11 115.5(15) C.sub.36 O.sub.4 C.sub.37 C.sub.13 C.sub.12 N.sub.3 115.1(14) N.sub.2 Pt.sub.1 N.sub.1 N.sub.3 C.sub.12 C.sub.11 102.6(14) N.sub.3 Pt.sub.2 N.sub.4 C.sub.12 C.sub.13 C.sub.14 115.2(16) N.sub.5 C.sub.53 C.sub.67.sup.1 C.sub.15 C.sub.14 C.sub.13 118.9(12) N.sub.5 C.sub.53 O.sub.5 C.sub.15 C.sub.14 C.sub.19 120.0 O.sub.5 C.sub.53 C.sub.67.sup.1 C.sub.19 C.sub.14 C.sub.13 121.0(12) O.sub.5 C.sub.54 C.sub.55 C.sub.14 C.sub.15 C.sub.16 120.0 C.sub.56 C.sub.55 C.sub.54 C.sub.17 C.sub.16 C.sub.15 120.0 N.sub.5 C.sub.55 C.sub.54 C.sub.16 C.sub.17 C.sub.18 120.0 N.sub.5 C.sub.55 C.sub.56 C.sub.19 C.sub.18 C.sub.17 120.0 C.sub.57 C.sub.56 C.sub.55 C.sub.18 C.sub.19 C.sub.14 120.0 C.sub.56 C.sub.57 C.sub.58 C.sub.21 C.sub.20 C.sub.3 109.8(17) C.sub.56 C.sub.57 C.sub.62 C.sub.22 C.sub.21 C.sub.20 119.8(13) C.sub.58 C.sub.57 C.sub.62 C.sub.22 C.sub.21 C.sub.26 120.0 C.sub.57 C.sub.58 C.sub.59 C.sub.26 C.sub.21 C.sub.20 120.2(13) C.sub.60 C.sub.59 C.sub.58 C.sub.21 C.sub.22 C.sub.23 120.0 C.sub.61 C.sub.60 C.sub.59 C.sub.22 C.sub.23 C.sub.24 120.0 C.sub.60 C.sub.61 C.sub.62 C.sub.25 C.sub.24 C.sub.23 120.0 C.sub.61 C.sub.62 C.sub.57 120.0 C.sub.24 C.sub.25 C.sub.26 120.0 N.sub.6 C.sub.63 C.sub.64 130(2) C.sub.25 C.sub.26 C.sub.21 120.0 N.sub.6 C.sub.63 O.sub.6 124(2) C.sub.28 C.sub.27 C.sub.46 117.3(19) O.sub.6 C.sub.63 C.sub.64 104(2) C.sub.28 C.sub.27 N.sub.2 106.9(18) C.sub.65 C.sub.64 C.sub.63 115.8(18) N.sub.2 C.sub.27 C.sub.46 107.7(17) C.sub.65 C.sub.64 C.sub.69 120.0 O.sub.2 C.sub.28 C.sub.27 107.6(18) C.sub.69 C.sub.64 C.sub.63 123.4(18) N.sub.2 C.sub.29 C.sub.30 120.9(18) C.sub.66 C.sub.65 C.sub.64 120.0 O.sub.2 C.sub.29 C.sub.30 121.3(19) C.sub.65 C.sub.66 C.sub.67 120.0 O.sub.2 C.sub.29 N.sub.2 116.9(18) C.sub.66 C.sub.67 C.sub.53.sup.1 119(2) C.sub.29 C.sub.30 C.sub.35 121.5(19) C.sub.68 C.sub.67 C.sub.53.sup.1 120(2) C.sub.31 C.sub.30 C.sub.29 116.9(19) C.sub.68 C.sub.67 C.sub.66 120.0 C.sub.31 C.sub.30 C.sub.35 118.9(19) C.sub.69 C.sub.68 C.sub.67 120.0 C.sub.30 C.sub.31 C.sub.32 117.5(18) C.sub.68 C.sub.69 C.sub.64 120.0 C.sub.33 C.sub.32 C.sub.31 119.1(18) O.sub.6 C.sub.70 C.sub.71 112(3) C.sub.32 C.sub.33 C.sub.36 114.4(18) C.sub.72 C.sub.71 C.sub.70 118(3) C.sub.34 C.sub.33 C.sub.32 117.5(18) C.sub.72 C.sub.71 N.sub.6 114(3) C.sub.34 C.sub.33 C.sub.36 127.9(19) N.sub.6 C.sub.71 C.sub.70 106(3) C.sub.35 C.sub.34 C.sub.33 126.2(19) C.sub.73 C.sub.72 C.sub.71 131(3) C.sub.34 C.sub.35 C.sub.30 119.3(19) C.sub.72 C.sub.73 C.sub.74 118.3(19) N.sub.4 C.sub.36 C.sub.33 121(2) C.sub.72 C.sub.73 C.sub.78 121.0(19) O.sub.4 C.sub.36 C.sub.33 119(2) C.sub.74 C.sub.73 C.sub.78 120.0 O.sub.4 C.sub.36 N.sub.4 120(2) C.sub.75 C.sub.74 C.sub.73 120.0 O.sub.4 C.sub.37 C.sub.38 105.4(16) C.sub.74 C.sub.75 C.sub.76 120.0 C.sub.37 C.sub.38 C.sub.39 108.9(19) C.sub.77 C.sub.76 C.sub.75 120.0 N.sub.4 C.sub.38 C.sub.37 104.9(18) C.sub.76 C.sub.77 C.sub.78 120.0 N.sub.4 C.sub.38 C.sub.39 104.6(17) C.sub.77 C.sub.78 C.sub.73 120.0 C.sub.40 C.sub.39 C.sub.38 114.9(16) C.sub.53 N.sub.5 C.sub.55 107(3) C.sub.41 C.sub.40 C.sub.39 120.8(12) C.sub.53 N.sub.5 Pt.sub.3 129(2) C.sub.41 C.sub.40 C.sub.45 120.0 C.sub.55 N.sub.5 Pt.sub.3 124(2) C.sub.45 C.sub.40 C.sub.39 119.2(12) C.sub.63 N.sub.6 C.sub.71 100(2) C.sub.40 C.sub.41 C.sub.42 120.0 C.sub.63 N.sub.6 Pt.sub.3 130.3(17) C.sub.41 C.sub.42 C.sub.43 120.0 C.sub.71 N.sub.6 Pt.sub.3 128(2) C.sub.42 C.sub.43 C.sub.44 120.0 C.sub.54 O.sub.S C.sub.53 101(3) C.sub.45 C.sub.44 C.sub.43 120.0 C.sub.70 O.sub.6 C.sub.63 96(2) C.sub.44 C.sub.45 C.sub.40 120.0 N.sub.5 Pt.sub.3 N.sub.6 176.0(11) C.sub.47 C.sub.46 C.sub.27 117.0(17) O.sub.7 N.sub.7 O.sub.8 126(3) C.sub.48 C.sub.47 C.sub.46 121.6(12) O.sub.7 N.sub.7 O.sub.9 123(2) C.sub.48 C.sub.47 C.sub.52 120.0 O.sub.8 N.sub.7 O.sub.9 104(3) .sup.1−X, +Y, −Z

(41) Condensation Reaction Between Benzophenone Imine and Trimethylsilitrile

(42) ##STR00004##

(43) 0.025 mL of benzophenone imine and 0.4 mL of trimethylsilitrile was taken and added to a 25 mL small flask, then, 1 mL of THF and 0.0157 g of the compound I were added, and stirred at room temperature for 8 hrs. A small number of the sample was taken for nuclear magnetic detection. The conversion rate was more than 99%; .sup.1H NMR (600 MHz, CDCl.sub.3, 27° C.), δ7.23-7.59 (m, 10H), 4.10 (s, 2H).

(44) Application of Anti-Cancer Activity

(45) Platinum complex designed and synthesized according to the structure of the active natural product in the present application exhibits strong inhibitory activity (ED.sub.50<10.0 μg/mL) for the treatment of A549 (lung cancer), KB (nasopharyngeal carcinoma), KB-VIn (anti-drug-resistant nasopharyngeal carcinoma) and human breast cancer (MCF-7). Therefore, it is expected that this compound can be used to treat various kinds of cancers, including lung cancer, breast cancer, oral cancer cells, and breast cancer cells. Part of this compound's anti-cancer activity test results are listed in Table 1:

(46) TABLE-US-00003 TABLE 1 Anti-cancer Activity Data of Platinum Complex (I) Cell line Human lung cancer Human oral cancer cells Human breast cancer cells Human breast cancer A549 cell MDA-MB-231 KB-VIN cell MCF-7 Average Standard Average Standard Average Standard Average Standard Sample value deviation value deviation value deviation value deviation Platinum complex 6.12 ±0.22 6.92 ±0.13 4.06 ±0.13 2.43 ±0.02 (I) Cisplatin 4.96 ±0.09 26.41 ±0.74 3.01 ±0.07 29.99 ±0.93