Kinetic Control in the Regioselective Alkylation of Pterin Sensitizers: A Synthetic, Photochemical and Theoretical Study

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

Boston, Massachusetts

Congreso; 256th American Chemical Society (ACS) National Meeting & Exposition; 2018

American Chemical Society (ACS)

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