Synthesis of water‐soluble phthalocyanines containing 1‐methyl‐1H‐imidazole‐2‐thiol: Investigation of DNA nuclease, α‐glucosidase inhibitory, and photo‐physicochemical properties

Abstract

In this work, we have presented on the synthesis and characterization of novel 3‐(1‐methyl‐1 H ‐imidazole‐2‐thiol)phthalonitrile ( 1 ) as a ligand and its nonperipherally (M = 2H ( 2 ), Zn(II) ( 3 ), and GaCl(III) ( 4 )) phthalocyanines and their highly water‐soluble hydrochloride derivatives ( 2a–4a ), containing 1‐methyl‐1 H ‐imidazole‐2‐thiol substituents. All compounds were supported by FT‐IR, UV–Vis, 1 H‐NMR, 13 C‐NMR, and MALDI‐TOF mass spectra. The molecular structure of the novel compound ( 1 ) and its intermolecular interactions have been elucidated by analyzing the results of X‐ray diffraction measurements. In order to determine the supercoiled pBR322 plasmid DNA nuclease properties of compounds ( 2a–4a ), agarose gel electrophoresis was used. The plasmid DNA nuclease did not observe without light irradiation on increasing concentrations ( 2a–4a ). When irradiated at 10 and 20 J/cm 2 , the band intensities changed on agarose gel, displaying photonuclease activity on supercoiled pBR322 plasmid DNA of compounds ( 2a–4a ); 4a had the highest photonuclease activities in a concentration‐dependent manner at 10 and 20 J/cm 2 . The in vitro α‐glucosidase inhibitory effects of compounds ( 2a–4a ) were investigated to determine whether they can be used in potential agents for diabetes mellitus. Compounds ( 2a–4a ) showed higher inhibitory effects than acarbose (63.03 ± 2.14 μM) against α‐glucosidase enzyme. Lineweaver–Burk analysis showed that K m increased and V max remained the same on increasing concentrations of compounds ( 2a–4a ). The finding results claimed that the compounds inhibited α‐glucosidase enzyme via competitive manner. Dixon plots showed that K i values of compounds ( 2a–4a ) were 14.70 ± 0.70, 11.20 ± 0.50, and 12.60 ± 0.20 μM, respectively. Besides, the effect of including metal ion on photochemical and photophysical features of the compounds was studied in DMSO and water, comparatively. The compounds gave high singlet oxygen quantum yields (Φ Δ = 0.86 for ( 4a ), 0.77 for ( 3a ), and 0.59 for ( 2a )) in DMSO. The results showed that the compounds are also very suitable for photodynamic therapy applications.