Theoretical scales of hydrogen bond acidity and basicity for application in QSAR/QSPR studies and drug design. Partitioning of aliphatic compounds.
Phenomenological analysis of existing hydrogen bond (HB) donor and acceptor scales and apparent physical considerations have enabled the establishment of new quantitative scales of hydrogen bond basicity and acidity. Chemical structures represented by molecular graphs and the orbital electronegativities of Hinze and Jaffe are utilized as an input data. The scales obtained correlate well with several experimental solvent polarity scales such as and, pK(HB), and E(T)(30). To demonstrate the applicability of the new quantities, we have applied them to seven equilibrium partitioning data sets: octanol-water, hexadecane-water, chloroform-water, gas-water, gas-octanol, gas-hexadecane, and gas-chloroform partition coefficients. The hydrogen bond descriptors when supplemented by a cavity-forming term and a dipolarity term show high performance in correlations of the partition coefficients of aliphatic compounds. These new HB descriptors can be used in studying hydrogen bonding and fluid phase equilibria as well as scoring functions in ligand docking and descriptors in ADME evaluations.
Oliferenko
Alexander A
AA
Department of Chemistry, Moscow State University, Moscow, 119899 Russia.
Oliferenko
Polina V
PV
Huddleston
Jonathan G
JG
Rogers
Robin D
RD
Palyulin
Vladimir A
VA
Zefirov
Nikolai S
NS
Katritzky
Alan R
AR
D015195:Drug Design; D004983:Ethanolamines / Q000737:chemistry; D019855:Ethylene Glycol / Q000737:chemistry; D005740:Gases / Q000737:chemistry; D006221:Halothane / Q000737:chemistry; D006860:Hydrogen Bonding; D021281:Quantitative Structure-Activity Relationship; D014867:Water / Q000737:chemistry
D004983:Ethanolamines; D005740:Gases; D014867:Water; C020283:diethanolamine; D019855:Ethylene Glycol; D006221:Halothane