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Density functional theory calculations of hydrogen bonding energies of drug molecules
KTH, School of Biotechnology (BIO), Theoretical Chemistry.
Department of Chemistry, University of Copenhagen.
KTH, School of Biotechnology (BIO), Theoretical Chemistry.ORCID iD: 0000-0003-0007-0394
Biovitrum AB, Stockholm.
Show others and affiliations
2006 (English)In: Journal of Molecular Structure, ISSN 0022-2860, E-ISSN 1872-8014, Vol. 776, no 1-3, 61-68 p.Article in journal (Refereed) Published
Abstract [en]

Hydrogen bonding energies of several drug molecules have been calculated using hybrid density functional theory with inclusion of basis set superposition error corrections. The calculated total hydrogen bonding energy of each drug molecule has been compared with the result of a conceptually simple additive model, from which the summation of hydrogen bonding energies of individual polar groups present in the drug molecule are considered. It is shown that the validity of the additive model is strongly conditional, and to some extent predictable: In cases where the hydrogen bonding group is isolated the addition model can be of relevance, while in cases where the hydrogen bonding groups are interconnected through pi-conjugation rings or chains of the drug molecules it introduces substantial errors. It is suggested that such strong cooperative effects of hydrogen bonds should always be taken into account for evaluation of the hydrogen bonding energies of drug molecules.

Place, publisher, year, edition, pages
2006. Vol. 776, no 1-3, 61-68 p.
Keyword [en]
Hydrogen bond energies; Drug molecules; Density functional theory
National Category
Chemical Engineering
Identifiers
URN: urn:nbn:se:kth:diva-7177DOI: 10.1016/j.theochem.2006.06.042ISI: 000242433800007Scopus ID: 2-s2.0-33749430410OAI: oai:DiVA.org:kth-7177DiVA: diva2:12107
Note
QC 20100630Available from: 2007-05-25 Created: 2007-05-25 Last updated: 2010-12-03Bibliographically approved
In thesis
1. Microscopic Interpretations of Drug Solubility
Open this publication in new window or tab >>Microscopic Interpretations of Drug Solubility
2007 (English)Doctoral thesis, comprehensive summary (Other scientific)
Place, publisher, year, edition, pages
Stockholm: KTH, 2007. x, 48 p.
Series
Trita-BIO-Report, ISSN 1654-2312 ; 2007:7
Keyword
pharmaceutical chemistry, physical chemistry, molecular physics, computer science
National Category
Chemical Engineering
Identifiers
urn:nbn:se:kth:diva-4393 (URN)978-91-7178-691-3 (ISBN)
Public defence
2007-05-29, FA 32, AlbaNova, Stockholm, 10:00
Opponent
Supervisors
Note
QC 20100630Available from: 2007-05-25 Created: 2007-05-25 Last updated: 2010-06-30Bibliographically approved
2. Microscopic views of drug solubility
Open this publication in new window or tab >>Microscopic views of drug solubility
2006 (English)Licentiate thesis, comprehensive summary (Other scientific)
Abstract [en]

The development of computational models for predicting drug solubility has increased drastically during the last decades. Nevertheless these models still have diffculties to estimate the aqueous solubility as accurate as desired. In this thesis di erent aspects that are known to have a large impact on the aqueous solubility of a molecule have been studied in detail using various theoretical methods with intension to provide microscopic view on drug solubility. The rst aspect studied is the hydrogen bond energies. Eight drug molecules have been calculated using density functional theory and the validity of additive model that has often been used in solubility models is examined. The impact of hydrogen bonds in Infrared and Raman spectra of three commonly used drug molecules has also been demonstrated. The calculated spectra are found to be in good agreement with the experimental data. Another aspect that is important in solubility models is the volume that a molecule occupies when it is dissolved in water. The volume term and its impact on the solvation energy has therefore also been calculated using three di erent methods. It was shown that the calculated volume di ered signi cantly dependent on which method that had been used, especially for larger molecules.

Most of the solubility models assume the solute molecule to be in the bulk of the solvent. The molecular behavior at the water/gas interface has been investigated to see how it di ers from bulk. It was seen that the concentration close to the interface was almost three times higher than in the bulk. The increase in concentration close to the surface depends on the larger gap between the interface energy and the gas phase energy than between the bulk energy and the gas phase energy.

Place, publisher, year, edition, pages
Stockholm: KTH, 2006. 43 p.
National Category
Industrial Biotechnology
Identifiers
urn:nbn:se:kth:diva-3940 (URN)91-7178-312-1 (ISBN)
Presentation
2006-05-03, 00:00
Note
QC 20101109Available from: 2006-05-09 Created: 2006-05-09 Last updated: 2010-11-09Bibliographically approved

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