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Context <p>Anthracycline anticancer antibiotics from <i>Streptomyces peucetius</i> show high affinity for nucleobases. This study uses quantum mechanical density functional theory (DFT) to investigate interactions between doxorubicin (DOX) tautomers and the guanine-cytosine (GC) base pair. Intermolecular distances and interaction energies reveal structural relationships and stabilization. Interaction energy studies show that DOX-GC has greater binding affinity and greater stability in the aqueous phase as compared to that in gaseous phase. Interestingly, the tautomer which show greater affinity for GC in the gas phase is different from the one in the aqueous phase. Reduced density gradient (RDG) scatter plots and quantum theory of atoms in molecules (QTAIM) confirm the presence of hydrogen bonds and its strength. Natural bond orbital (NBO) analysis elucidates donor–acceptor orbital interactions. These findings provide an understanding of the intermolecular interactions between DOX tautomers and the GC base pair, which is likely to provide insight into the molecular basis for DOX’s anticancer activity and therapeutic efficacy.</p> Methods <p>DFT calculations were performed using the B3LYP functional with a 6-31G(d,p) basis set in the Gaussian 09 package, including solvent effects through the integral equation formalism polarizable continuum model (IEF-PCM). Topological analysis and quantum theory of atoms in molecules (QTAIM) studies were conducted using the Multiwfn program, while non-covalent interactions were analysed using visual molecular dynamics (VMD) software.</p> Graphical Abstract <p></p>

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Interaction of tautomers of doxorubicin with guanine-cytosine base pair: a density functional theory study

  • 期刊论文

  • 发表日期：

    2025年3月3日

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  • Angarag Kashyap,
  • Kripangkar Choudhury,
  • Pradyumna Mazumdar,
  • Diganta Choudhury

摘要

Context

Anthracycline anticancer antibiotics from Streptomyces peucetius show high affinity for nucleobases. This study uses quantum mechanical density functional theory (DFT) to investigate interactions between doxorubicin (DOX) tautomers and the guanine-cytosine (GC) base pair. Intermolecular distances and interaction energies reveal structural relationships and stabilization. Interaction energy studies show that DOX-GC has greater binding affinity and greater stability in the aqueous phase as compared to that in gaseous phase. Interestingly, the tautomer which show greater affinity for GC in the gas phase is different from the one in the aqueous phase. Reduced density gradient (RDG) scatter plots and quantum theory of atoms in molecules (QTAIM) confirm the presence of hydrogen bonds and its strength. Natural bond orbital (NBO) analysis elucidates donor–acceptor orbital interactions. These findings provide an understanding of the intermolecular interactions between DOX tautomers and the GC base pair, which is likely to provide insight into the molecular basis for DOX’s anticancer activity and therapeutic efficacy.

Methods

DFT calculations were performed using the B3LYP functional with a 6-31G(d,p) basis set in the Gaussian 09 package, including solvent effects through the integral equation formalism polarizable continuum model (IEF-PCM). Topological analysis and quantum theory of atoms in molecules (QTAIM) studies were conducted using the Multiwfn program, while non-covalent interactions were analysed using visual molecular dynamics (VMD) software.

Graphical Abstract