Lipophilic Decyl Chain–Pterin Conjugates with Sensitizer Properties

Abstract

A new series of decyl chain [-(CH)CH] pterin conjugates have been investigated by photochemical and photophysical methods, and with theoretical solubility calculations. To synthesize the pterins, a nucleophilic substitution (S2) reaction was used for the regioselective coupling of the alkyl chain to the O site over the N site. However, the O-alkylated pterin converts to N-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 (Φ) and increased singlet oxygen quantum yields (Φ). It is shown that the DMF-condensed pterins were more photostable compared to the N- 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 a wider series of lipophilic, photooxidatively active pterins.

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

“…Figure shows the 1 O 2 emission that was detected for CapC when exciting at 366 nm. The 1 O 2 quantum yield (Φ ∆ ) obtained was 0.40 ± 0.01, which is quite good and is similar to the Φ ∆ values reported for O ‐ and N ‐decyl‐pterins 1 – 4 (Φ ∆ = 0.35 to 0.50) .…”

“…Having the same Φ F might be attributed to the fact that CapC has the chain attached to the substituent group and not directly to the ring, thereby not affecting the chromophore directly. In contrast, previously synthesized decyl‐pterins 1 – 4 , which have the chain attached to the ring , have Φ F an order of magnitude lower than CapC. Fluorescence emission was also study for CapC in methanol.…”

“…Fluorescence properties of CapC were studied in acetonitrile solution. Acetonitrile was chosen in order to compare CapC's fluorescence properties with the previously reported O ‐ and N ‐decyl‐pterins 1 – 4 , also done in acetonitrile . CapC showed an absorption spectrum similar to the one previously observed for the acid form of CapC in methanol/water (Fig.…”

“…). This spectral shifting pattern is typical of the aromatic water‐soluble pterins and was not observed for O ‐ and N ‐decyl‐pterins 1 – 4 , since the alkylation to the amide group eliminated the acidic site. Therefore, these results offer further support for the structure of CapC as deduced by NMR analysis ( vide supra ); in which, the structure is capable of the acid–base equilibrium depicted in Fig.…”

“…Over the past 6–8 years, “smart” compounds that possess dual fluorescence sensing and singlet oxygen sensitizing properties have become a hot topic , with success reported in dual function image‐guided and photodynamic therapy applications (PDT) . Indeed, our previous O ‐ and N ‐decyl‐pterins possessed good singlet oxygen quantum yields (Φ ∆ ), but had poor fluorescence quantum yields (Φ F ) some 4–30 fold less compared to native pterin, thereby fulfilling only two of three facets, even though a minor fluorescence increase was observed when intercalated in the membrane . As a result, we surmised that the low Φ F was related to the position of the alkylation, as the chain is attached to the aromatic ring, significantly reducing their capacity as fluorescent imaging probes in lipid membranes.…”