Highly specific G-quadruplex recognition covering physiological pH range by a new water-soluble cationic porphyrin with low self-aggregation tendency

Abstract

A new water-soluble cationic porphyrin derivative m-TMPyEOPP (5,10,15,20-tetrakis{4-[2-(O-(N-methylpyridyl)ethoxyl]oxyphenly}porphyrin) has been designed, synthesized, and fully characterized. This porphyrin derivative combines the advantages of two cationic porphyrins used in G-quadruplex recognition and stabilization studies, i.e., the widely investigated G-quadruplex ligand TMPyP4 and TMPipEOPP reported by us. That is to say, the presence of four bulky side-arm substituents endows the m-TMPyEOPP derivative with the capacity for colorimetric and fluorescence-based recognition of G-quadruplexes with high specificity. By virtue of almost negligible pH-dependent self-aggregation, and hence reduced single- and double-stranded DNA-templated aggregation behavior, it can also work well under acidic conditions. By combining the fluorescence signals obtained at different excitation wavelengths (690 or 260 nm), specific G-quadruplex recognition can be achieved by m-TMPyEOPP in the pH range 5.0–7.5, which almost covers the physiological pH range. Ratiometric signal output mode might confer G-quadruplex recognition with high accuracy, reliability and repeatability. This work demonstrates that the aggregation behaviours of water-soluble cationic porphyrins can be controlled by adjusting the nature of the substituents on their side arms, thus endowing them with different G-quadruplex-specific recognition abilities suitable for different pH conditions.