The emergence of antimicrobial resistance, exemplified
by methicillin-resistant Staphylococcus aureus (MRSA), poses a grave threat
to public health globally. Over time, MRSA has evolved resistance
to multiple antibiotics, challenging conventional treatment strategies.
The relentless adaptability of MRSA underscores the urgent need for
innovative and targeted antimicrobial approaches to combat this resilient
pathogen. Ancient knowledge and practices, along with scientific evidence,
have established that metallic copper, and its organic coordination
complexes can act as potential antibacterial substances. In search
of a smart and effective antimicrobial against MRSA, we designed,
synthesized, and characterized a bidentate copper(II) ligand complex
(SG-Cu) utilizing a comprehensive array of analytical techniques,
including ESI-MS, elemental analysis, X-ray photoelectron spectroscopy,
electron paramagnetic resonance spectroscopy, and others. Antibacterial
efficacy and mechanism of action of the complex were assessed through
bacterial growth analyses, bacterial membrane perturbation assays,
ROS elicitation assays, and field emission scanning electron microscopy.
SG-Cu was found to maintain robust biocompatibility against the mammalian
cell lines HEK-293, WI-38, and NIH/3T3. Remarkably, SG-Cu demonstrated
significant biofilm disruptive tendency evidenced by the retardation
of sliding motility, reduction in slime production, reduction in biofilm
viability, and enhanced biofilm eradication, both in vitro and in urinary catheters. In vivo studies on murine
excisional wounds, with SG-Cu impregnated in a palmitic acid conjugated
NAVSIQ hexapeptide (PA-NV) hydrogel, revealed the sustained release
of SG-Cu from the gel matrix, facilitating accelerated wound healing
and effective wound disinfection. This multifaceted investigation
highlights the potential of SG-Cu as a versatile option for combating
MRSA infections and promoting wound healing, solidifying its claim
to be developed into a viable therapeutic.