Spin Selectivity in Chiral Linked Systems

"This is the peer reviewed version of the following article: Ageeva, Aleksandra A., Ekaterina A. Khramtsova, Ilya M. Magin, Denis A. Rychkov, Peter A. Purtov, Miguel A. Miranda, and Tatyana V. Leshina. 2018. "Spin Selectivity in Chiral Linked Systems." Chemistry - A European Journal 24 (15). Wiley: 3882-92. doi:10.1002/chem.201705863, which has been published in final form at https://doi.org/10.1002/chem.201705863. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Self-Archiving."[EN] This work has shown spin selectivity in electron transfer (ET) of diastereomers of (R,S)-naproxen-(S)-N-methylpyrrolidine and (R,S)-naproxen-(S)-tryptophan dyads. Photoinduced ET in these dyads is interesting because of the still unexplained phenomenon of stereoselectivity in the drug activity of enantiomers. The chemically induced dynamic nuclear polarization (CIDNP) enhancement coefficients of (R,S)-diastereomers are double those of the (S,S)-analogue. These facts are also interesting because spin effects are among the most sensitive, even to small changes in spin and molecular dynamics of paramagnetic particles. Therefore, CIDNP reflects the difference in magnetoresonance parameters (hyperfine interaction constants (HFIs), g-factor difference) and lifetimes of the paramagnetic forms of (R,S)- and (S,S)-diastereomers. The difference in HFI values for diastereomers has been confirmed by a comparison of CIDNP experimental enhancement coefficients with those calculated. Additionally, the dependence of the CIDNP enhancement coefficients on diastereomer concentration has been observed for the naproxen-N-methylpyrrolidine dyad. This has been explained by the participation of ET in homo-(R,S-R,S or S,S-S,S) and hetero-(R,S-S,S) dimers of dyads. In this case, the effectivity of ET, and consequently, CIDNP, is supposed to be different for (R,S)- and (S,S)-homodimers, heterodimers, and monomers. The possibility of dyad dimer formation has been demonstrated by using high-resolution X-ray and NMR spectroscopy techniques.The work was supported by the Russian Foundation for Fundamental Research (14-03-00192).Ageeva, A.; Khramtsova, E.; Magin, I.; Richkov, D.; Purtov, P.; Miranda Alonso, MÁ.; Leshina, T. (2018). Spin Selectivity in Chiral Linked Systems. Chemistry - A European Journal. 24(15):3882-3892. https://doi.org/10.1002/chem.201705863S388238922415Lin, G.-Q., Zhang, J.-G., & Cheng, J.-F. (2011). Overview of Chirality and Chiral Drugs. Chiral Drugs, 3-28. doi:10.1002/9781118075647.ch1Lin, G.-Q., You, Q.-D., & Cheng, J.-F. (Eds.). (2011). Chiral Drugs. doi:10.1002/9781118075647Krasulova, K., Siller, M., Holas, O., Dvorak, Z., & Anzenbacher, P. (2015). Enantiospecific effects of chiral drugs on cytochrome P450 inhibitionin vitro. 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Effect of Amino Group Charge on the Photooxidation Kinetics of Aromatic Amino Acids

The kinetics of the photooxidation of aromatic amino acids histidine (His), tyrosine (Tyr), and tryptophan (Trp) by 3,3′,4,4′-benzophenonetetracarboxylic acid (TCBP) has been investigated in aqueous solutions using time-resolved laser flash photolysis and time-resolved chemically induced dynamic nuclear polarization. The pH dependence of quenching rate constants is measured within a large pH range. The chemical reactivities of free His, Trp, and Tyr and of their acetylated derivatives, <i>N</i>-AcHis, <i>N</i>-AcTyr, and <i>N</i>-AcTrp, toward TCBP triplets are compared to reveal the influence of amino group charge on the oxidation of aromatic amino acids. The bimolecular rate constants of quenching reactions between the triplet-excited TCBP in the fully deprotonated state and tryptophan, histidine, and tyrosine with a positively charged amino group are <i>k</i>_q = 2.2 × 10⁹ M^–1 s^–1 (4.9 < pH < 9.4), <i>k</i>_q = 1.6 × 10⁹ M^–1 s^–1 (6.0 < pH < 9.2), and <i>k</i>_q = 1.5 × 10⁹ M^–1 s^–1 (4.9 < pH < 9.0), respectively. Tryptophan, histidine, and tyrosine with a neutral amino group quench the TCBP triplets with the corresponding rate constants <i>k</i>_q = 8.0 × 10⁸ M^–1 s^–1 (pH > 9.4), <i>k</i>_q = 3.0 × 10⁸ M^–1 s^–1 (pH > 9.2), and <i>k</i>_q = (4.0–10.0) × 10⁸ M^–1 s^–1 (9.0 < pH < 10.1) that are close to those for the N-acetylated derivatives. Thus, it has been established that the presence of charged amino group changes oxidation rates by a significant factor; i.e., His with a positively charged amino group quenches the TCBP triplets 5 times more effectively than <i>N</i>-AcHis and His with a neutral amino group. The efficiency of quenching reaction between the TCBP triplets and Tyr and Trp with a positively charged amino group is about 3 times as high as that of both Tyr and Trp with a neutral amino group, <i>N</i>-AcTyr and <i>N</i>-AcTrp