Electronic Structure and Partial Charge Distribution of Doxorubicin in Different Molecular Environments

• Published in: Chemphyschem Vol. 16; no. 7; pp. 1451 - 1460
• Main Authors: Poudel, Lokendra, Wen, Amy M., French , Roger H., Parsegian, V. Adrian, Podgornik, Rudolf, Steinmetz , Nicole F., Ching, Wai-Yim
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 18.05.2015; WILEY‐VCH Verlag; Wiley Subscription Services, Inc
• Subjects: ab initio calculations; Deoxyribonucleic acid; DNA; DNA - chemistry; Doxorubicin - chemistry; electronic structure; Electrons; intercalations; Models, Molecular; Molecular Structure; Quantum Theory; solvent effects; solvent effects; ab initio calculations; DNA; intercalations; electronic structure
• ISSN: 1439-4235; 1439-7641
• DOI: 10.1002/cphc.201402893

The electronic structure and partial charge of doxorubicin (DOX) in three different molecular environments—isolated, solvated, and intercalated in a DNA complex—are studied by first‐principles density functional methods. It is shown that the addition of solvating water molecules to DOX, together with the proximity to and interaction with DNA, has a significant impact on the electronic structure as well as on the partial charge distribution. Significant improvement in estimating the DOX–DNA interaction energy is achieved. The results are further elucidated by resolving the total density of states and surface charge density into different functional groups. It is concluded that the presence of the solvent and the details of the interaction geometry matter greatly in determining the stability of DOX complexation. Ab initio calculations on realistic models are an important step toward a more accurate description of the long‐range interactions in biomolecular systems. Environmental response: The electronic structure and partial charges of doxorubicin (DOX) in three different molecular environments—isolated, solvated, and intercalated in a DNA complex (see picture)—are studied by ab initio calculations. Solvating water molecules and the proximity to and interaction with DNA have a significant impact on the electronic structure and partial‐charge distribution of DOX.