Department of Chemistry, Brooklyn College, City University of New York, Brooklyn, NY.
Ph.D. Program in Chemistry, The Graduate Center of the City University of New York, New York, NY.
Photochem Photobiol. 2018 Sep;94(5):834-844. doi: 10.1111/php.12905. Epub 2018 Mar 15.
Alkylation patterns and excited-state properties of pterins were examined both experimentally and theoretically. 2D NMR spectroscopy was used to characterize the pterin derivatives, revealing undoubtedly that the decyl chains were coupled to either the O4 or N3 sites on the pterin. At a temperature of 70°C, the pterin alkylation regioselectively favored the O4 over the N3. The O4 was also favored when using solvents, in which the reactants had increased solubility, namely N,N-dimethylformamide and N,N-dimethylacetamide, rather than solvents in which the reactants had very low solubility (tetrahydrofuran and dichloromethane). Density functional theory (DFT) computed enthalpies correlate to regioselectivity being kinetically driven because the less stable O-isomer forms in higher yield than the more stable N-isomer. Once formed these compounds did not interconvert thermally or undergo a unimolecular "walk" rearrangement. Mechanistic rationale for the factors underlying the regioselective alkylation of pterins is suggested, where kinetic rather than thermodynamic factors are key in the higher yield of the O-isomer. Computations also predicted greater solubility and reduced triplet state energetics thereby improving the properties of the alkylated pterins as O sensitizers. Insight on thermal and photostability of the alkylated pterins is also provided.
我们通过实验和理论研究考察了蝶呤的烷基化模式和激发态性质。二维 NMR 光谱用于表征蝶呤衍生物，明确证实了癸基链与蝶呤上的 O4 或 N3 位点相连。在 70°C 的温度下，蝶呤的烷基化具有区域选择性，优先选择 O4 而不是 N3。当使用反应物溶解度增加的溶剂（如 N,N-二甲基甲酰胺和 N,N-二甲基乙酰胺）而不是反应物溶解度非常低的溶剂（如四氢呋喃和二氯甲烷）时，O4 也受到青睐。密度泛函理论（DFT）计算的焓值与区域选择性相关，这是由动力学驱动的，因为不太稳定的 O-异构体比更稳定的 N-异构体以更高的产率形成。一旦形成，这些化合物不会在热或经历单分子“行走”重排中相互转化。提出了蝶呤区域选择性烷基化的因素的机理依据，其中动力学因素而非热力学因素是 O-异构体高产率的关键。计算还预测了更大的溶解度和降低的三重态能量，从而改善了作为 O 敏化剂的烷基化蝶呤的性质。还提供了对烷基化蝶呤的热和光稳定性的深入了解。
