Theoretical investigation of structure and electronic properties in <scp>Cisplatin</scp>‐citrate complexes

Cisplatin (CDDP) is an effective Platinum (Pt) based anticancer drug used in chemotherapy. However, its effectiveness is limited due to its instability in solvents, along with the side effects it causes due to DNA damage. Nanoparticles (NPs) were developed in vitro to address these issues by loading CDDP into various types of NPs, including metal, lipid, and biological NPs. Citrate was employed as a biocompatible compound in nanomedicine to reduce cytotoxicity and enhance stability. In our study, the physicochemical and electronic properties of CDDP and citrate have been investigated using density functional theory (DFT), with a comparison of their behavior in water and DMSO. Additionally, TD-DFT was applied to analyze the UV-Vis spectra results. Six complexes have been proposed to better understand the interaction between citrate and CDDP. The results demonstrated that the CDDP could form stable complexes with citrate in both water and DMSO, and the considered complexes exhibited UV-Vis spectra within the experiment range. The frontier orbitals, electron densities mapping, and electrostatic potential analysis revealed that complex 5, where citrate di-substituted on two chlorides, is the most likely and effective complex. In summary, our investigation sheds light on the potential of CDDP-citrate complexes to address the limitations of CDDP, offering insights into their stability and interaction in solvents and highlighting the promising efficacy of specific complex formations for future therapeutic applications.