Role of association in chiral catalysis: from asymmetric synthesis to spin selectivity

"This is the peer reviewed version of the following article: Ageeva, Aleksandra A., Ekaterina A. Khramtsova, Ilya M. Magin, Peter A. Purtov, Miguel A. Miranda, and Tatyana V. Leshina. 2018. Role of Association in Chiral Catalysis: From Asymmetric Synthesis to Spin Selectivity. Chemistry A European Journal 24 (70). Wiley: 18587 600. doi:10.1002/chem.201801625, which has been published in final form at https://doi.org/10.1002/chem.201801625. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving."[EN] The origin of biomolecules in the pre-biological period is still a matter of debate, as is the unclarified nature of the differences in enantiomer properties, especially for the medically important activity of chiral drugs. With regards to the first issue, significant progress was made in the last decade of the 20th century through experimental confirmation of Frank's popular theory on chiral catalysis in spontaneous asymmetric synthesis. Soai examined the chiral catalysis of the alkylation of achiral aldehydes by achiral reagents. Attempts to model this process demonstrated the key role of chiral compounds associates as templates for chiral synthesis. However, the elementary mechanism of alkylation and the role of free radicals in this process are still incompletely understood. Meanwhile, the influence of external magnetic fields on chiral enrichment in the radical path of alkylation has been predicted. In addition, the role of chiral dyad association in another radical process, electron transfer (ET), has been recently demonstrated by the following methods: chemically induced dynamic nuclear polarisation (CIDNP), NMR spectroscopy, XRD and photochemistry. The CIDNP analysis of ET in two dyads has revealed a phenomenon first observed for chiral systems, spin selectivity, which results in the difference between the CIDNP enhancement coefficients of dyad diastereomers. These dyads are linked systems consisting of the widespread drug (S)-naproxen (NPX) or its R analogue and electron donors, namely, (S)-tryptophan and (S)-N-methylpyrrolidine. Because NPX is one of the most striking examples of the difference in the therapeutic properties of enantiomers, the appearance of spin selectivity in dyads with (S)- and (R)-NPX and S donors can shed light on the chemical nature of these differences. This review is devoted to discussing the chemical nature of spin selectivity and the role of chiral associates in the chiral catalysis of an elementary radical reaction: ET in chiral dyads.The work was supported by the Russian Science Foundation (18-13-00047).Ageeva, A.; Khramtsova, E.; Magin, I.; Purtov, P.; Miranda Alonso, MÁ.; Leshina, T. (2018). Role of association in chiral catalysis: from asymmetric synthesis to spin selectivity. Chemistry - A European Journal. 24(70):18587-18600. https://doi.org/10.1002/chem.201801625S18587186002470Avalos, M., Babiano, R., Cintas, P., Jiménez, J. L., Palacios, J. C., & Barron, L. D. (1998). Absolute Asymmetric Synthesis under Physical Fields:  Facts and Fictions. Chemical Reviews, 98(7), 2391-2404. doi:10.1021/cr970096oLin, G.-Q., Zhang, J.-G., & Cheng, J.-F. (2011). Overview of Chirality and Chiral Drugs. Chiral Drugs, 3-28. doi:10.1002/9781118075647.ch1Liu, Y., & Gu, X.-H. (2011). Pharmacology of Chiral Drugs. Chiral Drugs, 323-345. doi:10.1002/9781118075647.ch8Frank, F. C. (1953). On spontaneous asymmetric synthesis. Biochimica et Biophysica Acta, 11, 459-463. doi:10.1016/0006-3002(53)90082-1Soai, K., Kawasaki, T., & Matsumoto, A. (2014). Asymmetric Autocatalysis of Pyrimidyl Alkanol and Its Application to the Study on the Origin of Homochirality. Accounts of Chemical Research, 47(12), 3643-3654. doi:10.1021/ar5003208Soai, K., Kawasaki, T., & Matsumoto, A. (2014). The Origins of Homochirality Examined by Using Asymmetric Autocatalysis. The Chemical Record, 14(1), 70-83. doi:10.1002/tcr.201300028Soai, K., Matsumoto, A., & Kawasaki, T. (2017). Asymmetric Autocatalysis and the Origins of Homochirality of Organic Compounds. An Overview. Advances in Asymmetric Autocatalysis and Related Topics, 1-30. doi:10.1016/b978-0-12-812824-4.00001-0Matsumoto, A., Kawasaki, T., & Soai, K. (2017). Structural Study of Asymmetric Autocatalysis by X-Ray Crystallography. Advances in Asymmetric Autocatalysis and Related Topics, 183-202. doi:10.1016/b978-0-12-812824-4.00010-1Schiaffino, L., & Ercolani, G. (2010). Mechanism of the Asymmetric Autocatalytic Soai Reaction Studied by Density Functional Theory. Chemistry - A European Journal, 16(10), 3147-3156. doi:10.1002/chem.200902543Buono, F. G., & Blackmond, D. G. (2003). Kinetic Evidence for a Tetrameric Transition State in the Asymmetric Autocatalytic Alkylation of Pyrimidyl Aldehydes†. Journal of the American Chemical Society, 125(30), 8978-8979. doi:10.1021/ja034705nGridnev, I. D., & Vorobiev, A. K. (2012). Quantification of Sophisticated Equilibria in the Reaction Pool and Amplifying Catalytic Cycle of the Soai Reaction. ACS Catalysis, 2(10), 2137-2149. doi:10.1021/cs300497hGridnev, I. D., Serafimov, J. M., & Brown, J. M. (2004). Solution Structure and Reagent Binding of the Zinc Alkoxide Catalyst in the Soai Asymmetric Autocatalytic Reaction. Angewandte Chemie International Edition, 43(37), 4884-4887. doi:10.1002/anie.200353572Gridnev, I. D., Serafimov, J. M., & Brown, J. M. (2004). Solution Structure and Reagent Binding of the Zinc Alkoxide Catalyst in the Soai Asymmetric Autocatalytic Reaction. Angewandte Chemie, 116(37), 4992-4995. doi:10.1002/ange.200353572Noble-Terán, M. E., Cruz, J.-M., Micheau, J.-C., & Buhse, T. (2018). A Quantification of the Soai Reaction. ChemCatChem, 10(3), 642-648. doi:10.1002/cctc.201701554Girard, C., & Kagan, H. B. (1998). Nonlinear Effects in Asymmetric Synthesis and Stereoselective Reactions: Ten Years of Investigation. Angewandte Chemie International Edition, 37(21), 2922-2959. doi:10.1002/(sici)1521-3773(19981116)37:213.0.co;2-1Girard, C., & Kagan, H. B. (1998). Nichtlineare Effekte bei asymmetrischen Synthesen und stereoselektiven Reaktionen. Angewandte Chemie, 110(21), 3088-3127. doi:10.1002/(sici)1521-3757(19981102)110:213.0.co;2-aNoble-Terán, M. E., Buhse, T., Cruz, J.-M., Coudret, C., & Micheau, J.-C. (2016). Nonlinear Effects in Asymmetric Synthesis: A Practical Tool for the Discrimination between Monomer and Dimer Catalysis. ChemCatChem, 8(10), 1836-1845. doi:10.1002/cctc.201600216Blackmond, D. G. (2000). Kinetic Aspects of Nonlinear Effects in Asymmetric Catalysis. Accounts of Chemical Research, 33(6), 402-411. doi:10.1021/ar990083sMatsumoto, A., Abe, T., Hara, A., Tobita, T., Sasagawa, T., Kawasaki, T., & Soai, K. (2015). Crystal Structure of the Isopropylzinc Alkoxide of Pyrimidyl Alkanol: Mechanistic Insights for Asymmetric Autocatalysis with Amplification of Enantiomeric Excess. Angewandte Chemie International Edition, 54(50), 15218-15221. doi:10.1002/anie.201508036Matsumoto, A., Abe, T., Hara, A., Tobita, T., Sasagawa, T., Kawasaki, T., & Soai, K. (2015). Crystal Structure of the Isopropylzinc Alkoxide of Pyrimidyl Alkanol: Mechanistic Insights for Asymmetric Autocatalysis with Amplification of Enantiomeric Excess. Angewandte Chemie, 127(50), 15433-15436. doi:10.1002/ange.201508036Ashby, E. C., Lopp, I. G., & Buhler, J. D. (1975). Mechanisms of Grignard reactions with ketones. Polar vs. single electron transfer pathways. Journal of the American Chemical Society, 97(7), 1964-1966. doi:10.1021/ja00840a066Ashby, E. C. (1988). Single-electron transfer, a major reaction pathway in organic chemistry. An answer to recent criticisms. Accounts of Chemical Research, 21(11), 414-421. doi:10.1021/ar00155a005Hegstrom, R. A., & Kondepudi, D. K. (1996). Influence of static magnetic fields on chirally autocatalytic radical-pair reactions. Chemical Physics Letters, 253(3-4), 322-326. doi:10.1016/0009-2614(96)00248-5K. M. Salikhov Yu. N. Molin R. Z. Sagdeev A. L. Buchachenko Spin Polarization and Magnetic Effects in Radical Reactions 1984 Akademiai Kiado Budapest Hungary 65 72Welch, C. J., Zawatzky, K., Makarov, A. A., Fujiwara, S., Matsumoto, A., & Soai, K. (2017). Can the analyte-triggered asymmetric autocatalytic Soai reaction serve as a universal analytical tool for measuring enantiopurity and assigning absolute configuration? Organic & Biomolecular Chemistry, 15(1), 96-101. doi:10.1039/c6ob01939kAgeeva, A. A., Khramtsova, E. A., Magin, I. M., Rychkov, D. A., Purtov, P. A., Miranda, M. A., & Leshina, T. V. (2018). Spin Selectivity in Chiral Linked Systems. Chemistry - A European Journal, 24(15), 3882-3892. doi:10.1002/chem.201705863Khramtsova, E. A., Sosnovsky, D. V., Ageeva, A. A., Nuin, E., Marin, M. L., Purtov, P. A., … Leshina, T. V. (2016). Impact of chirality on the photoinduced charge transfer in linked systems containing naproxen enantiomers. Physical Chemistry Chemical Physics, 18(18), 12733-12741. doi:10.1039/c5cp07305gKhramtsova, E. A., Ageeva, A. A., Stepanov, A. A., Plyusnin, V. F., & Leshina, T. V. (2017). Photoinduced Electron Transfer in Dyads with (R)-/(S)-Naproxen and (S)-Tryptophan. Zeitschrift für Physikalische Chemie, 231(3). doi:10.1515/zpch-2016-0842Magin, I. M., Polyakov, N. E., Kruppa, A. I., Purtov, P. A., Leshina, T. V., Kiryutin, A. S., … Marin, M. L. (2016). Low field photo-CIDNP in the intramolecular electron transfer of naproxen–pyrrolidine dyads. Physical Chemistry Chemical Physics, 18(2), 901-907. doi:10.1039/c5cp04233jDuggan, K. C., Hermanson, D. J., Musee, J., Prusakiewicz, J. J., Scheib, J. L., Carter, B. D., … Marnett, L. J. (2011). (R)-Profens are substrate-selective inhibitors of endocannabinoid oxygenation by COX-2. Nature Chemical Biology, 7(11), 803-809. doi:10.1038/nchembio.663Duggan, K. C., Walters, M. J., Musee, J., Harp, J. M., Kiefer, J. R., Oates, J. A., & Marnett, L. J. (2010). Molecular Basis for Cyclooxygenase Inhibition by the Non-steroidal Anti-inflammatory Drug Naproxen. Journal of Biological Chemistry, 285(45), 34950-34959. doi:10.1074/jbc.m110.162982Miners, J. O., Coulter, S., Tukey, R. H., Veronese, M. E., & Birkett, D. J. (1996). Cytochromes P450, 1A2, and 2C9 are responsible for the human hepatic O-demethylation of R- and S-naproxen. Biochemical Pharmacology, 51(8), 1003-1008. doi:10.1016/0006-2952(96)85085-4Levkin, P. A., Kokorin, A. I., Schurig, V., & Kostyanovsky, R. G. (2006). Solid-state ESR differentiation between racemate versus enantiomer. Chirality, 18(4), 232-238. doi:10.1002/chir.20242Khlestkin, V. K., Glasachev, Y. I., Kokorin, A. I., & Kostyanovsky, R. G. (2004). ESR study of stereochemistry in chiral nitroxide radical crystals. Mendeleev Communications, 14(6), 318-320. doi:10.1070/mc2004v014n06abeh002055Mäurer, M., & Stegmann, H. B. (1990). Chiral recognition of diastereomeric esters and acetals by EPR and NMR investigations. Chemische Berichte, 123(8), 1679-1685. doi:10.1002/cber.19901230817Kreilick, R. W., Becher, J., & Ullman, E. F. (1969). Stable free radicals. V. Electron spin resonance studies of nitronylnitroxide radicals with asymmetric centers. Journal of the American Chemical Society, 91(18), 5121-5124. doi:10.1021/ja01046a032Schuler, P., Schaber, F.-M., Stegmann, H. B., & Janzen, E. (1999). Recognition of chirality in nitroxides using EPR and ENDOR spectroscopy. Magnetic Resonance in Chemistry, 37(11), 805-813. doi:10.1002/(sici)1097-458x(199911)37:113.0.co;2-kNaaman, R., & Waldeck, D. H. (2012). Chiral-Induced Spin Selectivity Effect. The Journal of Physical Chemistry Letters, 3(16), 2178-2187. doi:10.1021/jz300793yYin, P., Zhang, Z.-M., Lv, H., Li, T., Haso, F., Hu, L., … Liu, T. (2015). Chiral recognition and selection during the self-assembly process of protein-mimic macroanions. Nature Communications, 6(1). doi:10.1038/ncomms7475Ishida, Y., & Aida, T. (2002). Homochiral Supramolecular Polymerization of an «S»-Shaped Chiral Monomer:  Translation of Optical Purity into Molecular Weight Distribution. Journal of the American Chemical Society, 124(47), 14017-14019. doi:10.1021/ja028403hSato, K., Itoh, Y., & Aida, T. (2014). Homochiral supramolecular polymerization of bowl-shaped chiral macrocycles in solution. Chem. Sci., 5(1), 136-140. doi:10.1039/c3sc52449cDubinets, N. O., Safonov, A. A., & Bagaturyants, A. A. (2016). Structures and Binding Energies of the Naphthalene Dimer in Its Ground and Excited States. The Journal of Physical Chemistry A, 120(17), 2779-2782. doi:10.1021/acs.jpca.6b03761‘Excimer’ fluorescence VII. Spectral studies of naphthalene and its derivatives. (1965). Proceedings of the Royal Society of London. Series A. Mathematical and Physical Sciences, 284(1399), 551-565. doi:10.1098/rspa.1965.0080Jiménez, M. C., Pischel, U., & Miranda, M. A. (2007). Photoinduced processes in naproxen-based chiral dyads. Journal of Photochemistry and Photobiology C: Photochemistry Reviews, 8(3), 128-142. doi:10.1016/j.jphotochemrev.2007.10.001Kerr, H. E., Softley, L. K., Suresh, K., Hodgkinson, P., & Evans, I. R. (2017). Structure and physicochemical characterization of a naproxen–picolinamide cocrystal. Acta Crystallographica Section C Structural Chemistry, 73(3), 168-175. doi:10.1107/s2053229616011980Hatton, J. V., & Richards, R. E. (1962). Solvent effects in N.M.R. spectra of amide solutions. Molecular Physics, 5(2), 139-152. doi:10.1080/00268976200100141Muñoz, M. ., Ferrero, R., Carmona, C., & Balón, M. (2004). Hydrogen bonding interactions between indole and benzenoid-π-bases. Spectrochimica Acta Part A: Molecular and Biomolecular Spectroscopy, 60(1-2), 193-200. doi:10.1016/s1386-1425(03)00206-3Mäurer, M., Stegmann, H. B., Hiller, W., & Müller, B. (1992). Stereoelectronic and Steric Effects in the Synthesis and Recognition of Diastereomeric Ethers by NMR and EPR Spectroscopy. Chemische Berichte, 125(4), 857-865. doi:10.1002/cber.1992125041

Thermodynamic properties of nanodrops. Molecular dynamics simulations

Paper presented at the 9th International Conference on Heat Transfer, Fluid Mechanics and Thermodynamics, Malta, 16-18 July, 2012.dc201

Low field photo-CIDNP in the intramolecular electron transfer in naproxen-pyrrolidine dyads

[EN] Photoinduced processes with partial (exciplex) and full charge transfer in donor-acceptor systems are of interest because they are frequently used for modeling drug-protein binding. Low field photo-CIDNP (chemically induced dynamic nuclear polarization) for these processes in dyads, including the drug, (S)-and (R)-naproxen and (S)-N-methyl pyrrolidine in solutions with strong and weak permittivity have been measured. The dramatic influence of solvent permittivity on the field dependence of the N-methyl pyrrolidine H-1 CIDNP effects has been found. The field dependences of both (R, S)-and (S, S)-dyads in a polar medium are the curves with a single extremum in the area of the S-T+ terms intersection. Moreover, the CIDNP field dependences of the same protons measured in a low polar medium present curves with several extrema. The shapes of the experimental CIDNP field dependence with two extrema have been described using the Green function approach for the calculation of the CIDNP effects in the system without electron exchange interactions. The article discusses the possible causes of the differences between the CIDNP field dependence detected in a low-permittivity solvent with the strong Coulomb interactions and in a polar solvent.This study was supported by the grant 14-03-00-192 of the Russian Foundation of Basic Research. The authors are also deeply grateful to Professor Hans-Martin Vieth for the given opportunity to conduct experiments on his unique equipment.Magin, I.; Polyakov, N.; Kruppa, AI.; Purtov, P.; Leshina, TV.; Kiryutin, AS.; Miranda Alonso, MÁ.... (2016). Low field photo-CIDNP in the intramolecular electron transfer in naproxen-pyrrolidine dyads. Physical Chemistry Chemical Physics. 18(2):901-907. https://doi.org/10.1039/C5CP04233JS901907182Reece, S. Y., & Nocera, D. G. (2009). Proton-Coupled Electron Transfer in Biology: Results from Synergistic Studies in Natural and Model Systems. Annual Review of Biochemistry, 78(1), 673-699. doi:10.1146/annurev.biochem.78.080207.092132Richert, S., Rosspeintner, A., Landgraf, S., Grampp, G., Vauthey, E., & Kattnig, D. R. (2013). Time-Resolved Magnetic Field Effects Distinguish Loose Ion Pairs from Exciplexes. Journal of the American Chemical Society, 135(40), 15144-15152. doi:10.1021/ja407052tAich, S., & Basu, S. (1998). Magnetic Field Effect: A Tool for Identification of Spin State in a Photoinduced Electron-Transfer Reaction. The Journal of Physical Chemistry A, 102(4), 722-729. doi:10.1021/jp972264mVayá, I., Pérez-Ruiz, R., Lhiaubet-Vallet, V., Jiménez, M. C., & Miranda, M. A. (2010). Drug–protein interactions assessed by fluorescence measurements in the real complexes and in model dyads. Chemical Physics Letters, 486(4-6), 147-153. doi:10.1016/j.cplett.2009.12.091Werner, U., & Staerk, H. (1995). Magnetic Field Effect in the Recombination Reaction of Radical Ion Pairs: Dependence on Solvent Dielectric Constant. The Journal of Physical Chemistry, 99(1), 248-254. doi:10.1021/j100001a038Kattnig, D. R., Rosspeintner, A., & Grampp, G. (2008). Fully Reversible Interconversion between Locally Excited Fluorophore, Exciplex, and Radical Ion Pair Demonstrated by a New Magnetic Field Effect. Angewandte Chemie International Edition, 47(5), 960-962. doi:10.1002/anie.200703488Kattnig, D. R., Rosspeintner, A., & Grampp, G. (2011). Magnetic field effects on exciplex-forming systems: the effect on the locally excited fluorophore and its dependence on free energy. Phys. Chem. Chem. Phys., 13(8), 3446-3460. doi:10.1039/c0cp01517bVayá, I., Lhiaubet-Vallet, V., Jiménez, M. C., & Miranda, M. A. (2014). Photoactive assemblies of organic compounds and biomolecules: drug–protein supramolecular systems. Chem. Soc. Rev., 43(12), 4102-4122. doi:10.1039/c3cs60413fPolyakov, N. E., Taraban, M. B., & Leshina, T. V. (2004). Photo-CIDNP Study of the Interaction of Tyrosine with Nifedipine. An Attempt to Model the Binding Between Calcium Receptor and Calcium Antagonist Nifedipine¶. Photochemistry and Photobiology, 80(3), 565. doi:10.1562/0031-8655(2004)0802.0.co;2Cao, H., Fujiwara, Y., Haino, T., Fukazawa, Y., Tung, C.-H., & Tanimoto, Y. (1996). Magnetic Field Effects on Intramolecular Exciplex Fluorescence of Chain-Linked Phenanthrene andN,N-Dimethylaniline: Influence of Chain Length, Solvent, and Temperature. Bulletin of the Chemical Society of Japan, 69(10), 2801-2813. doi:10.1246/bcsj.69.2801Magin, I. M., Polyakov, N. E., Khramtsova, E. A., Kruppa, A. I., Tsentalovich, Y. P., Leshina, T. V., … Marin, M. L. (2011). Spin effects in intramolecular electron transfer in naproxen-N-methylpyrrolidine dyad. Chemical Physics Letters, 516(1-3), 51-55. doi:10.1016/j.cplett.2011.09.057Khramtsova, E. A., Plyusnin, V. F., Magin, I. M., Kruppa, A. I., Polyakov, N. E., Leshina, T. V., … Miranda, M. A. (2013). Time-Resolved Fluorescence Study of Exciplex Formation in Diastereomeric Naproxen–Pyrrolidine Dyads. The Journal of Physical Chemistry B, 117(50), 16206-16211. doi:10.1021/jp4083147Magin, I. M., Purtov, P. A., Kruppa, A. I., & Leshina, T. V. (2005). Peculiarities of Magnetic and Spin Effects in a Biradical/Stable Radical Complex (Three-Spin System). Theory and Comparison with Experiment. The Journal of Physical Chemistry A, 109(33), 7396-7401. doi:10.1021/jp051115ySubramanian, V., Bellubbi, B. S., & Sobhanadri, J. (1993). Dielectric studies of some binary liquid mixtures using microwave cavity techniques. Pramana, 41(1), 9-20. doi:10.1007/bf02847313Acemioğlu, B., Arık, M., Efeoğlu, H., & Onganer, Y. (2001). Solvent effect on the ground and excited state dipole moments of fluorescein. Journal of Molecular Structure: THEOCHEM, 548(1-3), 165-171. doi:10.1016/s0166-1280(01)00513-9Grosse, S., Gubaydullin, F., Scheelken, H., Vieth, H.-M., & Yurkovskaya, A. V. (1999). Field cycling by fast NMR probe transfer: Design and application in field-dependent CIDNP experiments. Applied Magnetic Resonance, 17(2-3), 211-225. doi:10.1007/bf03162162Magin, I. M., Polyakov, N. E., Khramtsova, E. A., Kruppa, A. I., Stepanov, A. A., Purtov, P. A., … Marin, M. L. (2011). Spin Chemistry Investigation of Peculiarities of Photoinduced Electron Transfer in Donor–Acceptor Linked System. Applied Magnetic Resonance, 41(2-4), 205-220. doi:10.1007/s00723-011-0288-3C. K. Mann and K. K.Barnes, Electrochemical Reactions in Nonaqueous Systems, M. Dekker, New York, 1970N. S. Landolt-Bornstein , Numerical Data and Functional Relationship in Science and Technology: Magnetic Properties of Free Radicals, Springer-Verlag, Berlin, 1988Grigoryants, V. M., Anisimov, O. A., & Molin, Y. N. (1982). Study of the radical-cations of triethylamine and benzene derivatives by the optical detection of the EPR spectra of radical-ion Pairs. Journal of Structural Chemistry, 23(3), 327-333. doi:10.1007/bf00753466Bargon, J. (1977). CIDNP from geminate recombination of radical-ion pairs in polar solvents. Journal of the American Chemical Society, 99(25), 8350-8351. doi:10.1021/ja00467a054Purtov, P. A., & Doktorov, A. B. (1993). The Green function method in the theory of nuclear and electron spin polarization. I. General theory, zero approximation and applications. Chemical Physics, 178(1-3), 47-65. doi:10.1016/0301-0104(93)85050-iPurtov, P. A., Doktorov, A. B., & Popov, A. V. (1994). The green function method in the theory of nuclear and electron spin polarization. II. The first approximation and its application in the CIDEP theory. Chemical Physics, 182(2-3), 149-166. doi:10.1016/0301-0104(93)e0449-6K. M. Salikhov , Yu. N.Molin, R. Z.Sagdeev and A. L.Buchachenko, in Spin Polarization and Magnetic Field Effects in Radical, ed. Yu. N. Molin, Akademiai Kiado, Budapest, 1984Polyakov, N. E., Purtov, P. A., Leshina, T. V., Taraban, M. B., Sagdeev, R. Z., & Salikhov, K. M. (1986). Application of the semiclassical description of hyperfine interaction to studies of the dependence of the CIDNP effect on an external magnetic field. Chemical Physics Letters, 129(4), 357-361. doi:10.1016/0009-2614(86)80358-xShiotani, M., Sjoeqvist, L., Lund, A., Lunell, S., Eriksson, L., & Huang, M. B. (1990). An ESR and theoretical ab initio study of the structure and dynamics of the pyrrolidine radical cation and the neutral 1-pyrrolidinyl radical. The Journal of Physical Chemistry, 94(21), 8081-8090. doi:10.1021/j100384a020De Kanter, F. J. J., den Hollander, J. A., Huizer, A. H., & Kaptein, R. (1977). Biradical CIDNP and the dynamics of polymethylene chains. Molecular Physics, 34(3), 857-874. doi:10.1080/00268977700102161De Kanter, F. J. J., Kaptein, R., & Van Santen, R. A. (1977). Magnetic field dependent biradical CIDNP as a tool for the study of conformations of polymethylene chains. Chemical Physics Letters, 45(3), 575-579. doi:10.1016/0009-2614(77)80093-6Tsentalovich, Y. P., Yurkovskaya, A. V., Sagdeev, R. Z., Obynochny, A. A., Purtov, P. A., & Shargorodsky, A. A. (1989). Kinetics of nuclear polarization in the geminate recombination of biradicals. Chemical Physics, 139(2-3), 307-315. doi:10.1016/0301-0104(89)80143-0Popov, A. V., Purtov, P. A., & Yurkovskaya, A. V. (2000). Calculation of CIDNP field dependences in biradicals in the photolysis of large-ring cycloalkanones. Chemical Physics, 252(1-2), 83-95. doi:10.1016/s0301-0104(99)00293-1Magin, I. M., Shevel’kov, V. S., Obynochny, A. A., Kruppa, A. I., & Leshina, T. V. (2002). CIDNP study of the third spin effect on the singlet–triplet evolution in radical pairs. Chemical Physics Letters, 357(5-6), 351-357. doi:10.1016/s0009-2614(02)00544-4Schulten, K., & Wolynes, P. G. (1978). Semiclassical description of electron spin motion in radicals including the effect of electron hopping. The Journal of Chemical Physics, 68(7), 3292-3297. doi:10.1063/1.436135Kalneus, E. V., Stass, D. V., & Molin, Y. N. (2005). Typical applications of MARY spectroscopy: Radical ions of substituted benzenes. Applied Magnetic Resonance, 28(3-4), 213-229. doi:10.1007/bf03166757Kruppa, A. I., Leshina, T. V., Sagdeev, R. Z., Korolenko, E. C., & Shokhirev, N. V. (1987). Low-field CIDNP study of photoinduced electron transfer reactions. Chemical Physics, 114(1), 95-101. doi:10.1016/0301-0104(87)80022-

Impact of chirality on the photoinduced charge transfer in linked systems containing naproxen enantiomers

[EN] The model reaction of photoinduced donor-acceptor interaction in linked systems (dyads) has been used to study the comparative reactivity of a well-known anti-inflammatory drug, (S)-naproxen (NPX) and its (R)-isomer. (R)- or (S)-NPX in these dyads is linked to (S)-N-methylpyrrolidine (Pyr) using a linear or cyclic amino acid bridge (AA or CyAA), to give (R)-/(S)-NPX-AA-(S)-Pyr flexible and (R)-/(S)-NPX-CyAA-(S)-Pyr rigid dyads. The donor-acceptor interaction is reminiscent of the binding (partial charge transfer, CT) and electron transfer (ET) processes involved in the extensively studied inhibition of the cyclooxygenase enzymes (COXs) by the NPX enantiomers. Besides that, both optical isomers undergo oxidative metabolism by enzymes from the P450 family, which also includes ET. The scheme proposed for the excitation quenching of the (R)- and (S)-NPX excited state in these dyads is based on the joint analysis of the chemically induced dynamic nuclear polarization (CIDNP) and fluorescence data. The H-1 CIDNP effects in this system appear in the back electron transfer in the biradical-zwitterion (BZ), which is formed via dyad photoirradiation. The rate constants of individual steps in the proposed scheme and the fluorescence quantum yields of the local excited (LE) states and exciplexes show stereoselectivity. It depends on the bridge's length, structure and solvent polarity. The CIDNP effects (experimental and calculated) also demonstrate stereodifferentiation. The exciplex quantum yields and the rates of formation are larger for the dyads containing (R)-NPX, which let us suggest a higher contribution from the CT processes with the (R)-optical isomer.The work was supported by the Russian Foundation for Fundamental Research (14-03-00192, 14-03-00692). All QS calculations were carried out on a cluster computer in the regional center for shared computer equipment at the Ufa Institute of Chemistry of RAS.Khramtsova, E.; Sosnovsky, D.; Ageeva, A.; Nuin Plá, NE.; Marín García, ML.; Purtov, P.; Borisevich, S.... (2016). Impact of chirality on the photoinduced charge transfer in linked systems containing naproxen enantiomers. Physical Chemistry Chemical Physics. 18(18):12733-12741. https://doi.org/10.1039/C5CP07305GS1273312741181