A SYSTEM AND METHOD FOR PROMOTING CHEMICAL REACTIONS
20210379557 · 2021-12-09
Inventors
- Ron NAAMAN (Yarkona, IL)
- Claudio FONTANESI (Rehovot, IL)
- Francesco TASSINARI (Rehovot, IL)
- Suryakant MISHRA (Rehovot, IL)
- Eyal CAPUA (Rehovot, IL)
- Yossef Paltiel (Maskeret Batya, IL)
- Shira Yochelis (Ness Ziona, IL)
- Tzuriel METZGER (Jerusalem, IL)
Cpc classification
B01J19/087
PERFORMING OPERATIONS; TRANSPORTING
B01J2219/0852
PERFORMING OPERATIONS; TRANSPORTING
B01J2219/0809
PERFORMING OPERATIONS; TRANSPORTING
International classification
B01J19/08
PERFORMING OPERATIONS; TRANSPORTING
Abstract
A system and method for use in synthesis and promoting interactions of chiral molecules. The system can include: a container configured for containing fluid mixture comprising one or more reactant molecules and at least one surface comprising ferromagnetic or paramagnetic material located to be in at least partial contact with reactants in said container. The ferromagnetic of paramagnetic material can be magnetizable with magnetization direction perpendicular to said at least one surface, thereby providing chiral selective synthesis from said one or more reactant molecules. The technique can enable selective interactions of enantiomers of selected handedness of chiral molecules or formation of selected enantiomers from achiral molecule reactants.
Claims
1. A system for use in synthesis of molecules, comprising: a container configured for containing fluid mixture comprising one or more reactant molecules, and at least one surface comprising ferromagnetic or paramagnetic material, located to be in at least partial contact with reactants in said container, said ferromagnetic or paramagnetic material being magnetizable with magnetization direction perpendicular to said at least one surface, thereby providing chiral selective synthesis from said one or more reactant molecules.
2. The system of claim 1, wherein said at least one surface comprises structured substrate comprising at least one layer of ferromagnetic or paramagnetic material.
3. The system of claim 2, wherein said structured substrate comprises at least one surface layer having affinity for adsorption with one or more selected reactants, thereby enabling molecular interactions between reactants at vicinity of the at least one surface.
4. The system of claim 3, further comprising at least one of: (i) at least one type of reactant molecules pre-adsorbed on said at least one surface, the pre-adsorbed reactant molecules being capable of selectively interacting with molecules of selected handedness in said fluid mixture or (ii) one or more additional types of reactant molecules being absorbed in corresponding one or more additional layers associated with enantiospecific interactions.
5. (canceled)
6. The system of claim 1, wherein said at least one surface is associated with an electrode providing electrical contact with said fluid mixture, thereby promoting electro-chemical reaction at vicinity of the at least one surface.
7. The system of claim 1, wherein said at least one surface comprising ferromagnetic or paramagnetic material is mounted to be selectively placed to be in contact with reactants in said container, and to be placed out of contact with said reactants.
8. The system of claim 1, configured for selectively promoting chemical reactions for enantiomers of selected handedness of chiral molecules in accordance with direction of magnetization perpendicular to said at least one surface being up or down with respect to said at least one surface.
9. A system for use in synthesis of molecules comprising: a container configured for containing fluid mixture that comprising one or more types of chiral molecules; an electrode arrangement comprising at least first and second electrodes, being configured for applying an electric field on said fluid mixture; said first electrode comprises at least one ferromagnetic or paramagnetic material providing at least one interface with said fluid mixture, said at least one ferromagnetic or paramagnetic material being selectively magnetized in up or down direction perpendicular to surface of said first electrode; said second electrode being located at a predetermined distance from said first electrode and being electrically insulated therefrom; wherein magnetization of said first electrode provides spin selectivity in electrons transmission in interaction with molecules in said fluid mixture, thereby providing enantioselective interaction with molecules in said fluid mixture; and a power unit configured for providing electrical voltage and current between said first and second electrodes.
10. The system of claim 9, wherein said first electrode comprises at least one ferromagnetic or paramagnetic material, said system further comprises at least one field generating unit configured to selectively apply magnetic field onto said first electrode providing selected magnetization direction of said first electrode.
11. The system of claim 9, configured for at least one of synthesis or separation of chiral molecules or at least one enantiospecific reaction such of selected enantiomer from racemic mixture.
12. (canceled)
13. The system of claim 11, wherein the enantiospecific reaction is electrochemical oxidation or reduction reactions.
14. The system of claim 9, wherein at least said first electrode is mounted to be selectively insert into said container for selectively start and stop said interaction with reactants in said fluid mixture.
15. A method for use in molecular synthesis, the method comprising: providing at least one substrate having magnetization perpendicular to surface of said substrate; bringing said substrate in contact with one or more types of reactant molecules for promoting one or more molecular reactions on or in vicinity of surface of said substrate; wherein magnetization direction of said at least one substrate provides spin selectivity of electrons participating in said one or more molecular reactions resulting in enantioselective reactions.
16. The method of claim 15, wherein said one or more molecular reactions comprise electro-chemical reaction, the method further comprises applying selected electrical voltage on said at least one substrate thereby receiving or donating electrons of selected spin polarization to perform said one or more molecular reactions.
17. The method of claim 15, further comprising adsorbing one or more selected reactants onto said surface of said at least one substrate prior to bringing said substrate in contact with one or more types of reactant molecules, thereby providing enantioselective interactions between said one or more types of reactant molecules and said one or more selected reactants adsorbed on said surface.
18. The method of claim 15, wherein said one or more types of reactant molecules comprise chiral molecules, said enantioselective reactions provide at least one of reactions of enantiomers of one handedness selected in accordance with direction of magnetization of said at least one substrate or formation of chiral products having handedness selected in accordance with direction of magnetization of said at least one substrate.
19. (canceled)
20. (canceled)
21. The method of claim 18, further comprising transferring said at least one substrate to container comprising buffer solution for removing molecules of said selected handedness from said at least one substrate to enable enantiomer separation by physical adsorption enantiomers of selected handedness.
22. A method for use in separation of chiral molecules, the method comprising: providing at least one substrate having magnetization perpendicular to surface of said substrate; bringing said substrate in contact with mixture of chiral molecules for a selected time and removing said substrate from said mixture to remove the adsorbed molecules therefrom; wherein magnetization direction of said at least one substrate provides preferred adsorption of molecules of one enantiomer over molecules of the opposite enantiomer thereby removing molecules of a selected enantiomer from said mixture.
23. The method of claim 22, further comprising at least one of washing adsorbed molecules from said substrate in a second container, thereby providing a solution of substantially enantiomer pure mixture or repeatedly bring said substrate into contact with said mixture of chiral molecules for selected time and washing said substrate in a second container to thereby provide a continuous separation process.
24. (canceled)
25. The method of claim 22, comprising using a plurality of substrates and repeating said separation process with each of said substrates.
Description
BRIEF DESCRIPTION OF THE DRAWINGS
[0047] In order to better understand the subject matter that is disclosed herein and to exemplify how it may be carried out in practice, embodiments will now be described, by way of non-limiting example only, with reference to the accompanying drawings, in which:
[0048]
[0049]
[0050]
[0051]
[0052]
[0053]
DETAILED DESCRIPTION OF EMBODIMENTS
[0054] Reference is made to
[0055] The obtained CD signals indicate that after the electrochemical reaction, one enantiomer remains in the solution, while the molecules of the other enantiomer have been reduced, providing increase CD signal with respect to the racemic mixture. This result demonstrates enantioselective electrochemical redox process of camphor sulfonic acid, so that one enantiomer was reduced and the other remain mainly unaffected. It should be noted that the enantioselectivity in electrochemical reaction (e.g. electro-oxidization, electro-hydrogenation) is not specific to camphor sulfonic acid and may be used with various other molecules.
[0056] As described above, when a molecule approaches a substrate (being a surface or other molecules), charge rearrangement occurs, and an induced dipole is formed, in which fractions of an electron or hole is located at the negative and positive poles respectively. A moving electron with its spin has a certain helicity, i.e. relation between the spin and the linear momentum of the electron. The similarity between the electron helicity and chirality of a molecules is exemplified in
[0057] Typically, if the ground state of the electron is a singlet state, the spins at the electric poles will be anticorrelated, so that the total spin of the molecule remains zero. As described above, this effect varies with the adsorption of molecules on the magnetized substrates depending on the spin of the electron pointing towards the surface. Accordingly, for a chemical bond to be formed between the molecule and the substrate, the electron that is donated by the molecule and the one donated by the magnetized substrate to the bond formation, should be of opposite spins. This effect is similar upon interaction between two molecules. The electrons in the magnetized substrate that can participate in the bond with the molecule, have a well-defined spin due to magnetization of the substrate. Therefore, the electron donated by the molecule must or should have the opposite spin. This leaves the molecule with (partially) unpaired electron in the electric pole farther away from the substrate and this electron has the same spin as the ferromagnetic layer, as long as the system is coherent.
[0058] The present technique utilizes such spin preference in interaction between molecules and magnetized substrates (or between molecules in the vicinity of magnetized substrates). Such spin preference holds not only for covalent bonding but for any strength of interaction between the molecules and the ferromagnetic substrate, being adsorption, electron exchange, etc. More specifically, magnetized surface/substrate can donate or receive electron of a selected spin. Additionally, when molecules are adsorbed on the surface, the unpaired electron located on the opposite pole of the molecule, away from the surface, is generally similarly spin polarized. This extends the effect of the surface magnetization and resulting chiral selectivity to molecule-molecule interaction. More specifically, such unpaired, spin polarized electron of molecules may interact in enantio-specific manner with additional chiral molecules, as well as with non-chiral molecules. This enables promoting chiral selective interactions, where chiral molecules of selected handedness participate in the interaction, while same molecules with opposite handedness do not take part in the reaction. Additionally, such spin selectivity of the electrons facilitating chemical reaction, may lead to selected chiral symmetry of reaction products, even if the initial reactants are non-chiral.
[0059] Reference is made to
[0060] As exemplified in
[0061] To remove the reaction products from the magnetized substrate 50, it may be transferred to a third container 76 including solvent material. The A-B product molecules are removed from the magnetized structure 50 and can be moved for further processing or use. At this stage, the A-B reaction products generally contain a high ratio of one enantiomer (e.g. concentration ratio of 0.8 to 1 of a selected enantiomer). The process may be repeated for production of further complex molecules and it may include additional stages such as washing the magnetized structure. It should also be noted that the magnetized structure may be used as electrode for one or more electrochemical reactions with reactants of selected handedness. This is exemplified in
[0062] The system 100 exemplified in
[0063] Reference is made to
[0064] The distance between the magnetized ferromagnetic substrate and the chiral molecules was achieved and controlled by selecting the length of the linker molecules. More specifically, the linker molecules, forming a monolayer of stationary phase, were composed of molecules with the general structure HS—(CH.sub.2).sub.X-1—COO.sup.−, where the thiol group acts to link the molecules to the substrate and the number X of carbon groups determined length of the linker. The tests were conducted several times using linker molecules of different lengths, i.e. different numbers X of carbon groups. The easy axis in this ferromagnetic Ni layer is set to be perpendicular to the substrate and it can be magnetized at the up direction (+) or down direction (−). The interaction of the chiral molecules with the stationary monolayer is based on electrostatic bonds. Two enantiomers of R or S 1-amino-2-propanol were prepared in ethanol (pH˜7) solvent for all or most experiments. In this situation of about pH-7, both the carboxyl group and the amine group are charged, so that an electrostatic interaction between them is possible. The hydroxyl group, apart from defining the chiral center, acts as an Fourier-transform infrared spectroscopy (FTIR) marker for stretch modes in the wavenumber range of 3200-3500 cm.sup.−1.
[0065]
[0066] The OH stretch signals appears in S enantiomer under down (−) magnetization direction at about 3300-3450 cm.sup.−1 after 2-minute interaction in
[0067] By changing the linker length, location of the interacting ends of the molecules with respect to the magnetized surface changes. Increased linker lengths results in decay of spin polarization of the electrons participating in the interaction, reducing selectivity of the interaction. The use of linker molecules of varying lengths enables to monitor this effect. The inventors have found that the decay of the selectivity is clearly noticed with linker length of more than 3 carbons (X=3), which relates to linker length of 6.3 Å under assumption of tetrahedral angle and 0.77 Å covalent radius of carbon in c-c bonding. Thus, the selectivity decays at distances larger than 6.3 Å. With any longer linkers, the interaction does not show selectivity with respect to chirality of the molecules and magnetization of the substrate. Thus, the adsorption rate, using linkers longer than 6.3 Å is similar for up or down magnetization and R or S enantiomers. At this case, the interaction shows similar characteristics to the case where no magnetization is applied on the surface. The system was verified also for mercaptohexanoic acid (with X=6) and mercaptooctanoic acid (with X=8). Both did not show any qualitative difference, there was no selective adsorption and the analyte adsorbed in the same rate under up or down or without magnetization. These results suggest that the length dependence decay is due to losing the electron spin coherency in the linker molecules biased by the magnetic field on the ferromagnet.
[0068] As indicated, at large distance (longer than length of 3 carbons' covalent bonds) electrostatic bonds may be created at the same rate with and without magnetic field for the two enantiomers. At these conditions the OH stretch signal appears after 30 minutes, indicating time of interaction between the 1-amino-2-propanol molecules and the linker molecules. Generally, if the interaction with the substrate is stronger, the first signal of the OH stretch is expected to appear faster, while if it is weaker the signal is expected to appear after longer interaction time. Table 1 exemplifies minimal absorption durations for different linker lengths and magnetizations, normalized by the time of adsorption with long linkers where enantioselectivity vanishes. More specifically, the time of the appearance of the OH stretch signal in FTIR measurements for interaction with short linkers is normalized by the time of appearance of the OH stretch signal after interaction with long linkers where the substrate magnetization does not play a role. In table 1, the first and the second rows are the normalized times relevant to reaction of R 1-amino-2-propanol, and the third and fourth last rows are the normalized times relevant to reaction of S 1-amino-2-propanol. The interaction rates were correlated to the first appearance of the OH stretch signal, defined by integrating the peak area having a signal that is two folds higher than that shown in FTIR of the TGA monomers. The measured time was measured and averaged over 5 samples. The time under up (+) magnetization direction for the R enantiomer is faster than under down (−) magnetization direction. The S enantiomer displays the opposite trend. When 4 carbons (7.5 Å) are used, no selective absorbance is achieved.
TABLE-US-00001 TABLE 1 Analyte, condition/ Thioglycolic Mercaptopropionic Mercaptobutiric Stationary phase acid acid acid (monolayer) (2 Carbons ~5 Å) (3 Carbons ~6.3 Å) (4 Carbons ~7.5 Å) (R)-1-Amino-2- ⅓ ½ 1 propanol magnetic field direction (+) (R)-1-Amino-2- 3 1.5 1 propanol magnetic field direction (−) (S)-1-Amino-2- 2 3 1 propanol magnetic field direction (+) (S)-1-Amino-2- 1/15 ⅓ 1 propanol magnetic field direction (−)
[0069] As shown in table 1, the use of short linking layers to magnetized surface provide enantioselective interactions. As indicated above, this is considered to be associated with the CISS exchange interactions being stronger due to spin polarization of interacting electrons. For enantiomers of selected handedness, weaker interaction is shown as well as longer adsorption rates for one magnetization direction, while in the opposite magnetization direction, shorter adsorption rates are shown. The enantiomers of opposite handedness behave similarly for opposite magnetization directions. The shorter the linkers the selectivity becomes stronger. For linkers having length associated with 2 carbon bonds, the selectivity reaches a factor of 9 for the R enantiomer and a factor of 30 for the S enantiomer. For linker length of 3 carbons, the selectivity reaches a factor of 3 for the R enantiomer and a factor of 9 for the S enantiomer. With 4 carbons linkers, the selectivity disappears.
[0070] To relate the asymmetrical electrostatic adsorption properties to magnetic spin, the same chemical layout was deposited on sensitive Hall devices based on GaAs/AlGaAs heterostructure with shallow 2D electron gas. Reference is made to
[0071]
[0072] The results above indicate stereo-chemistry and enantioselective reactions provided by promoting physical and chemical molecular interactions at the vicinity of magnetized surfaces. More specifically, the present technique provides enantioselective interactions on, or at selected distances (generally not exceeding 0.7 nm) from magnetized surface (being ferromagnetic or paramagnetic surface). Furthermore, the enantio-selective interactions are stable for relatively long period of time, in response to adsorption onto the magnetized surface.
[0073] Thus, the present technique provides for promoting enantioselective interaction between selected chiral molecules. Generally, unlike the conventional techniques using chromatographic systems with selected lock and key features that are specific for selected molecules. The present technique enables the use of physical bonds and CISS controlled reaction that provide generic differentiation between enantiomers, where similar system configuration provides enantioselective interactions to various reactants. Further, the present technique is also relevant for selective interactions using chiral, helical as well as non-chiral and non-helical molecules, where in the later cases, the selectivity is manifested in chirality of the reaction products. Accordingly, the present technique demonstrates spin-based chemistry, exemplifying selected enantioselective interactions where the interaction centers are on, or in vicinity of a surface having magnetization perpendicular to the surface.