Kinetic Control in the Alkylation of Pterin Photosensitizers: Synthetic, Photochemical, and Theoretical Studies

NILUKSHA WALALAWELA; MARIANA VIGNONI; MARÍA NOEL URRUTIA; SARAH BELH; EDYTA GREER; ANDRÉS H. THOMAS; ALEXANDER GREER

Tampa

Congreso; American Society for Photobiology (ASP) Biennial Meeting.; 2018

American Society for Photobiology

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 1O2 sensitizers . Insight on thermal and photostability of the alkylated pterins is also provided