Synthesis and Characterization of Heteroleptic Copper Complexes: As Prospective Antimicrobial, Cytotoxic and Antioxidative Agents

Abstract

Copper(I) halide complexes with N,Nʹ-disubstituted thioureas and triphenylphosphine have been synthesized by the reaction of halotris(triphenylphosphine)copper(I) and respective thioureas (121) at 60 °C. The newly synthesized complexes were fully characterized by various instrumental techniques like FT-IR, multinuclear (1H, 13C, 19F, 31P) NMR spectroscopy while elemental analyses were carried out using a CHNS analyzer and atomic absorption spectroscopy. Some of the copper(I)-N,Nʹ-disubstituted thiourea complexes (A3, A7, A9, A16, B1, B3, B4, B6, B13, B14, B18, B19, C1, C3, C8, C9, C10, C12, C14, and C15) were analyzed via single crystal XRD for structural elucidation. From single crystal XRD it has been identified that copper(I) adopted distorted tetrahedral geometry in coordination with sulphur (substituted thiourea), two phosphorus (triphenylphosphine) and halogen. Most of the complexes were stabilized by intramolecular hydrogen bonding. The synthesized complexes were screened for cytotoxicity (Brine shrimp), antibacterial, antifungal, antileishmanial, antioxidant and DNA binding studies. In Brine shrimp lethality assay complexes B17 and B11 were the most active with LC50 of 19.6 µg mL–1 and 20.1 µg mL–1, respectively. In case of antibacterial activities, in the chlorinated series (A), the most active complex against E. Aerogens was A15, against B. Bronchiseptaca it was A12 and against S. Typhimurium were A9 and A3 with ZOI value comparable to that of the reference commercial drug. Similarly, in the iodinated series (C), the most active complex against B. Bronchiseptaca was C13 and against S. Typhimurium it was C9 with ZOI values of 20±1.46 and 19±1.27 mm, respectively. Against A. fumagatus(Fungi) the most active complex was B14 with a ZOI value of 19.5±1.46 mm which was comparable to that of the reference value. In Leishmanicidal activity all the test samples were active against L. tropica with LC50 values in the range of 20 to 50 µg mL–1. In the assay of DPPH Free-Radical Scavenging, all the test samples were significantly active toward DPPH and the antioxidant activity of the complexes was found within the range of 54.96-62.67%. From UV-vis spectroscopy and molecular docking studies it has also been observed that copper(I) tetrahedral complexes interact strongly with the DNA via a groove binding mode. From molecular docking the highest value of Kb was found to be 1.08×105 for A12 which is attributed to the intra-strand cross linking of benzo[d]thiazol-2-yl of thiourea in the complex with DA17 and DT6 base pairs of DNA in addition to groove binding interactions.