Lipophilic Decyl Chain–Pterin Conjugates with Sensitizer Properties

BONESI, SERGIO M.; VIGNONI, MARIANA; GREER, ALEXANDER; WALALAWELA, NILUKSHA; THOMAS, ANDRÉS H.; BONESI, SERGIO M.; VIGNONI, MARIANA; GREER, ALEXANDER; WALALAWELA, NILUKSHA; THOMAS, ANDRÉS H.

MOLECULAR PHARMACEUTICS

AMER CHEMICAL SOC

Lugar: Washington; Año: 2018 vol. 15 p. 798 - 807

1543-8384

A new series of decyl chain [-(CH2)9CH3] pterin conjugates have been investigated by photochemical and photophysical methods, and with theoretical solubility calculations. To synthesize the pterins, a nucleophilic substitution (SN2) reaction was used for the regioselective coupling of the alkyl chain to the O site over the N3 site. However, the O-alkylated pterin converts to N3-alkylated pterin under basic conditions, pointing to a kinetic product in the former and a thermodynamic product in the latter. Two additional adducts were also obtained from an N-amine condensation of DMF solvent molecule as byproducts. In comparison to the natural product pterin, the alkyl chain pterins possess reduced fluorescence quantum yields (ΦF) and increased singlet oxygen quantum yields (ΦΔ). It is shown that the DMF-condensed pterins were more photostable compared to the N3- and O-alkylated pterins bearing a free amine group. The alkyl chain pterins efficiently intercalate in large unilamellar vesicles, which is a good indicator of their potential use as photosensitizers in biomembranes. Our study serves as a starting point where the synthesis can be expanded to produce wider series lipophilic, photooxidatively active pterins.