Lipophilic Decyl Chain–Pterin Conjugates with Sensitizer Properties

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

MOLECULAR PHARMACEUTICS

AMER CHEMICAL SOC

Año: 2018 vol. 15 p. 798 - 807

1543-8384

A new series of decyl chain [−(CH2)9CH3]pterinconjugates have been investigated by photochemical and photophysicalmethods, and with theoretical solubility calculations. To synthesize thepterins, a nucleophilic substitution (SN2) reaction was used for theregioselective coupling of the alkyl chain to the O site over the N3 site.However, the O-alkylated pterin converts to N3-alkylated pterin underbasic conditions, pointing to a kinetic product in the former and athermodynamic product in the latter. Two additional adducts were alsoobtained from an N-amine condensation of DMF solvent molecule asbyproducts. In comparison to the natural product pterin, the alkyl chainpterins possess reduced fluorescence quantum yields (ΦF) and increasedsinglet oxygen quantum yields (ΦΔ). It is shown that the DMF-condensedpterins were more photostable compared to the N3- and O-alkylatedpterins bearing a free amine group. The alkyl chain pterins efficiently intercalate in large unilamellar vesicles, which is a goodindicator of their potential use as photosensitizers in biomembranes. Our study serves as a starting point where the synthesis canbe expanded to produce a wider series of lipophilic, photooxidatively active pterins.