Abstrakt

Exploiting the natural affinity of vitamin B12 to accumulate in cancer cells is an attractive strategy for enhancing the effectiveness and minimizing the side effects of chemotherapy. To this end, a sophisticated protein-mediated transport mechanism must be considered in the design of novel therapeutics, alongside the kinetic and thermodynamic stability of cytostatic complexes. In this study, we subjected novel cyanocobalamin conjugates with platinum(II) complexes to computational and experimental characterization. Molecular docking against three vitamin B12 transport proteins [transcobalamin I (TCI), intrinsic factor (IF), transcobalamin II (TCII)] identified a spectrum of predicted binding free energies (ΔG ≈ −17.9 to +8.4 kcal mol−1), with most conjugates showing consistently favorable affinity toward proteins, especially IF and TCII, and only one unfavorable toward TCI. All compounds were synthesized via cyanide-bridged strategy and characterized by UV–Vis, IR, and HRMS, which confirm Pt(II) conjugation and preservation of characteristic cobalamin spectral features. Lipophilicity was quantified by logD measurements to provide a comparative metric relevant to membrane permeation and uptake. Taken together, the computational and spectroscopic data indicate that cobalamin–Pt(II) conjugation can produce species structurally compatible with B12 transport pathways, supporting further studies on serum stability, transporter-mediated uptake and in vitro cytotoxicity to assess their potential as targeted platinum(II) therapeutics.