Integrated Computational and Spectroscopic Analyses to unravel the Role of Cu(II) Coordination in Modulating Doxorubicin-DNA Binding
Year: 2026
Type: preprint
Abstract: Doxorubicin (DOX) is a clinically important anthracycline whose anticancer activity is closely associated with DNA binding. However, the structural basis by which metal coordination modulates DOX-DNA association remains poorly understood. Here, an integrated computational and spectroscopic approach was employed to elucidate the role of Cu(II) coordination in modulating the structure of DOX and its DNA binding. DFT, molecular docking, and molecular dynamics simulations established a stable intercalative association of DOX with DNA. At the same time, DFT-based characterization of Cu(II)-DOX revealed coordination-induced structural and electronic changes consistent with reduced conformational freedom and increased rigidity. This led to the hypothesis that Cu(II) coordination may favor an intercalation-compatible configuration of DOX. UV–Vis and competitive fluorescence studies experimentally supported Cu(II)-dependent modulation of DOX– DNA association, with UV–Vis analysis indicating a substantial tenfold increase in apparent DNA-binding affinity and fluorescence measurements confirming pronounced perturbation of DNA-associated ethidium bromide. Collectively, the findings establish a coherent relationship between Cu(II) coordination, DOX conformational modulation, and DNA recognition, highlighting metal coordination as a potential strategy for tuning the biomolecular interactions of anthracycline therapeutics.
Institutions: Sri Sathya Sai Institute of Higher Learning, SRM University
Language: English
Subfield: Oncology
Field: Medicine
Domain: Health Sciences
Open Access status: green
OpenAlex ID: W7213300151