The role of hydrogen bond acidity, i.e., the ability of chemicals to act as hydrogen bond donors (HBD), is a crucial element in pharmaceutical sciences and medicinal chemistry. It has been shown that the difference between log P values (Δlog P) obtained in two different biphasic systems is informative of the solutes HBD properties and thus useful in the prediction of drugs human fate. In this study, we collected from literature more than 200 experimental log Ptol (the logarithm of the partition coefficient P in the toluene/water system) values along with their corresponding log Poct (the logarithm of the partition coefficient P in the octanol/water system) values. The dataset was processed using a purposely-built in-house software to remove molecules that are potentially able to form IMHBs. On the remaining structures the Δlog Poct–tol (=log Poct – log Ptol) have been calculated and correlated with 82 VolSurf+ descriptors through a PLS model. Finally the Block Relevance (BR) analysis has been used to group the descriptors in six easy-to-interpret blocks and to show graphically the relevance of a certain block in the PLS model. BR analysis showed that the hydrogen bond donor (HBD) properties of the solutes mainly govern Δlog Poct–tol. This supports the use of Δlog Poct–tol to estimate HBD properties of solutes and its role in the intramolecular hydrogen bonding (IMHB) interpretation scheme recently reported in the literature.

The Block Relevance (BR) analysis supports the dominating effect of solutes hydrogen bond acidity on Δlog Poct–tol

ERMONDI, Giuseppe;VISCONTI, ALESSIA;ESPOSITO, Roberto;CARON, Giulia
2014

Abstract

The role of hydrogen bond acidity, i.e., the ability of chemicals to act as hydrogen bond donors (HBD), is a crucial element in pharmaceutical sciences and medicinal chemistry. It has been shown that the difference between log P values (Δlog P) obtained in two different biphasic systems is informative of the solutes HBD properties and thus useful in the prediction of drugs human fate. In this study, we collected from literature more than 200 experimental log Ptol (the logarithm of the partition coefficient P in the toluene/water system) values along with their corresponding log Poct (the logarithm of the partition coefficient P in the octanol/water system) values. The dataset was processed using a purposely-built in-house software to remove molecules that are potentially able to form IMHBs. On the remaining structures the Δlog Poct–tol (=log Poct – log Ptol) have been calculated and correlated with 82 VolSurf+ descriptors through a PLS model. Finally the Block Relevance (BR) analysis has been used to group the descriptors in six easy-to-interpret blocks and to show graphically the relevance of a certain block in the PLS model. BR analysis showed that the hydrogen bond donor (HBD) properties of the solutes mainly govern Δlog Poct–tol. This supports the use of Δlog Poct–tol to estimate HBD properties of solutes and its role in the intramolecular hydrogen bonding (IMHB) interpretation scheme recently reported in the literature.
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http://www.sciencedirect.com/science/article/pii/S0928098713004648
Lipophilicity; QSAR; BR analysis; IMHB
G.Ermondi; A.Visconti; R.Esposito; G.Caron
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Utilizza questo identificativo per citare o creare un link a questo documento: http://hdl.handle.net/2318/143546
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