Hybrid surfactants decorated with copper ions: aggregation behavior, antimicrobial activity and anti-proliferative effect

Abstract

In the present study, the emphasis is laid on the self aggregation behavior of copper based inorganic-organic hybrids in aqueous media. The two complexes, cationic hexadecyl pyridinium trichloro cuprate (1 : 1), [Cp](+)[CuCl3](-), and bishexadecylpyridinium tetrachloro cuprate (2 : 1), [Cp2](2+)[CuCl4](2-), were synthesized using the ligand insertion method. The complexes were characterized using elemental analysis, Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), nuclear magnetic resonance (NMR) and thermogravimetric analysis. The copper complexes were found to be thermally stable, and in the solid state, they possessed the perovskite arrangement with [Cp2](2+)[CuCl4](2-) exhibiting superior stability and crystallinity. The self aggregation behavior of the prepared complexes was analyzed in solution phase (in aqueous medium) using surface tension, conductivity, XRD and small angle neutron scattering (SANS). The results show that the presence of copper as a co-ion in both the stoichiometries results in lower critical micellization concentrations than their precursor. Micellization was thermodynamically spontaneous and micelles formed were ellipsoidal in shape and underwent a prolate ellipsoidal growth with an increase in the concentration of metallosurfactant, as estimated from the SANS. Furthermore, these metallosurfactants were investigated for biocompatibility (using hemolytic assay), antimicrobial activity (fungus and bacteria) and cytotoxicity using human cancerous cells. The hemolysis activity was found to depend on the aggregated state of the metallosurfactants, displaying the highest activity in the monomeric state, and the minimum for post micellar concentrations. The surfactants were found to enhance the antibacterial activity by twofold or more, with the addition of metal in both the stoichiometries. On the contrary, for anticancer and antifungal activities, barely any regular trend or generalization could be obtained. Nevertheless, the copper complexes exhibited high IC50 values for fR2 (healthy cells) signifying their higher safety in comparison to the cancerous cells.

Copper as an alternative antimicrobial coating for implants - an in vitro study

“…Copper ions attack the bacteria at different sites[44-46]. They can interact with the outer membrane of bacteria and subsequently disintegrate the bacterial cell wall which is known as the bacteriolytic effect.…”

Designed Meso‐macroporous Silica Framework Impregnated with Copper Oxide Nanoparticles for Enhanced Catalytic Performance

“…Cu‐CPC with molecular formula [CP] 2 + [CuCl 4 ] 2− was synthesized as reported previously . Briefly, CuCl 2 ⋅ 2 H 2 O and CPC were mixed in a 1:2 molar ratio in ethanol.…”

Synthesis, Characterization, and Investigation of the Antimicrobial Activity of Cetylpyridinium Tetrachlorozincate

“…proposed the use of cetylpyridinium tetrachlorozincate as a titrant for analysis of anionic surfactants. , In 2015, Kaur et al . synthesized (CP) 2 CuCl 4 and (CP)­CuCl 3 and demonstrated that the insertion of copper into the CPC moiety enhanced the antibacterial activity as compared to pure CPC . Although the antimicrobial properties of copper (Cu) have long been known, the realization of the Cu–cetylpyridinium conjugate technology for healthcare applications would be extremely challenging due to the potential for blue ( e.g ., Cu 2+ ) or yellow ( e.g ., [CP]­[CuCl 3 ] or [CP] 2 [CuCl 4 ]) staining associated with the d-orbital splitting of the copper ion.…”