Alkane Chain-extended Pterin Through a Pendent Carboxylic Acid Acts as Triple Functioning Fluorophore, 1O2 Sensitizer and Membrane Binder

Abstract

In order to develop a new long alkane chain pterin that leaves the pterin core largely unperturbed, we synthesized and photochemically characterized decyl pterin-6-carboxyl ester (CapC) that preserves the pterin amide group. CapC contains a decyl-chain at the carboxylic acid position and a condensed DMF molecule at the N2 position. Occupation of the long alkane chain on the pendent carboxylic acid group retains the acid-base equilibrium of the pterin headgroup due to its somewhat remote location. This new CapC compound has relatively high fluorescence emission and singlet oxygen quantum yields attributed to the lack of through-bond interaction between the long alkane chain and the pterin headgroup. The calculated lipophilicity is higher for CapC compared to parent pterin and pterin-6-carboxylic acid (Cap) and comparable to previously reported O- and N-decyl-pterin derivatives. CapC's binding constant Kb (8000 M-1 in L-α-phosphatidylcholine from egg yolk) and ΦF :Φ∆ ratio (0.26:0.40) point to a unique triple function compound, although the hydrolytic stability of CapC is modest due to its ester conjugation. CapC is capable of the general triple action not only as a membrane intercalator, but also fluorophore and 1 O2 sensitizer, leading to a "self-monitoring" membrane fluorescent probe and a membrane photodamaging agent.