Fluorescent di-(2-picolyl)amine based drug-like ligands and their Re(CO)3 complexes towards biological applications

Abstract

Herein we report two new fac-Re(I) tricarbonyl complexes, fac-[Re(CO)3(N(SO2)(1-nap)dpa)]PF6 (C1) and fac-[Re(CO)3(N(SO2)(2-nap)dpa)]PF6 (C2), of two naphthalene derivatized tridentate ligands (N(SO2)(1-nap)dpa (L1) and N(SO2)(2-nap)dpa (L2)) and one reported Re(I) complex, fac-[Re(CO)3(N(SO2Me2Nnap)dpa)]PF6 (C3), of a dansyl appended di-2-picolylamine ligand (N(SO2Me2Nnap)dpa (L3)). The properties of the compounds were elucidated using spectrophotometric measurements (UV–Vis, FTIR and 1H NMR). A single crystal X-ray study was carried out for the three ligands. The 1H NMR spectra of the three complexes obtained in DMSO‑d6 displayed two doublets (exo-CH and endo-CH) for the magnetically inequivalent methylene protons, compared to their uncoordinated ligands where the methylene protons show a singlet peak. The formation of the metal complexes was further supported by FTIR spectra in which the SN stretching band for the metal complexes appears at lower wavenumbers compared to that of the corresponding free ligands. In comparison with the uncoordinated ligands, the Re(I) complexes, C1 and C3, displayed a bathochromic shift while C2 showed a hypsochromic shift in the absorption spectra in methanol. The fluorescent maxima and the fluorescence quantum yield (ΦF) of L1 and L2 were 338 nm (ΦF = 0.056) and 343 nm (ΦF = 0.039), respectively. Interestingly, all the compounds except C2 showed excellent fluorescent emissions. Biologically, the compounds were investigated for their cytotoxicity in vitro on human lymphocytes following the Trypan blue dye exclusion method. It was observed that both Re(I) complexes as well as the ligands show low toxicity towards human lymphocytes at working concentrations below 10 mg/ml (L1, L2: 0.026 M, L3: 0.023 M, C1, C2, C3: 0.012 M). In silico studies revealed that the ligands are potential candidates for anti-inflammatory agents and this was further supported by molecular docking studies, in which they showed a higher affinity for Prostaglandin synthase 2. These drug-like molecules, having an affinity to bovine serum albumin, are thus potential drug leads for anti-inflammatory agents.