Theoretical Prediction of Hydrogen-Bond Basicity p<i>K</i><sub>BHX</sub>Using Quantum Chemical Topology Descriptors

Green, Anthony J; Popelier, Paul L. A.

doi:10.1021/ci400657c

Cited by 34 publications

(49 citation statements)

References 55 publications

(106 reference statements)

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“…A partial optimisation of the H‐bond complex leads to reasonable correlations between p K BHX and the calculated interaction energies, but no validation on an external test set was reported. Green et al 28. found reasonable linear correlations ( R 2 corr =0.91–0.97) between p K BHX measured for 41 HBAs with quantum chemical topology descriptors calculated for the complexes of these compounds with 5 different HBDs (water, methanol, 4‐fluorophenol, serine and methylamine).…”

Section: Introductionmentioning

confidence: 90%

“…Literature8–13) can potentially be used for this purpose, in support of experimental measurements, to characterise the individual H‐bond basicity of acceptor sites encountered in progesterone,31 cotinine,32 lobeline,33 myosmines,34 codeine and galanthamine 35. Performance of quantum chemical topology descriptors to treat polyfunctional molecules have also been demonstrated by Green et al 28. At the same time, heavy and time‐consuming quantum mechanics‐based approaches could hardly be recommended for virtual screening of large databases frequently used in computer‐aided drug‐ or material design.…”

Section: Introductionmentioning

confidence: 91%

“…Earlier, the modelling of thermodynamic parameters of the 1 : 1 H‐bond complexes has already been attempted through various approaches such as quantum chemical methods,7–12 linear free‐energy relationships (LFERs),13–17 empirical correlations18–24 and quantitative structure‐property relationships (QSPR) using results of quantum chemical calculations as descriptors 7–11, 25–28. The LFERs models by Raevsky15–17 and Abraham14 consider the free energy of H‐bond complexation as a product of the acceptor and donor parameters.…”

Section: Introductionmentioning

confidence: 99%

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Individual Hydrogen‐Bond Strength QSPR Modelling with ISIDA Local Descriptors: a Step Towards Polyfunctional Molecules

Ruggiu

Solov'ev

Marcou

et al. 2014

Molecular Informatics

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Here, we introduce new ISIDA fragment descriptors able to describe "local" properties related to selected atoms or molecular fragments. These descriptors have been applied for QSPR modelling of the H-bond basicity scale pKBHX , measured by the 1 : 1 complexation constant of a series of organic acceptors (H-bond bases) with 4-fluorophenol as the reference H-bond donor in CCl4 at 298 K. Unlike previous QSPR studies of H-bond complexation, the models based on these new descriptors are able to predict the H-bond basicity of different acceptor centres on the same polyfunctional molecule. QSPR models were obtained using support vector machine and ensemble multiple linear regression methods on a set of 537 organic compounds including 5 bifunctional molecules. They were validated with cross-validation procedures and with two external test sets. The best model displays good predictive performance on a large test set of 451 mono- and bifunctional molecules: a root-mean squared error RMSE=0.26 and a determination coefficient R(2) =0.91. It is implemented on our website (http://infochim.u-strasbg.fr/webserv/VSEngine.html) together with the estimation of its applicability domain and an automatic detection of potential H-bond acceptors.

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Section: Introductionmentioning

confidence: 90%

Section: Introductionmentioning

confidence: 91%

Section: Introductionmentioning

confidence: 99%

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Individual Hydrogen‐Bond Strength QSPR Modelling with ISIDA Local Descriptors: a Step Towards Polyfunctional Molecules

Ruggiu

Solov'ev

Marcou

et al. 2014

Molecular Informatics

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“…The predictive power of BCP properties‐based descriptors is illustrated with the QTMS approach of Popelier and coworkers, and the work of Buttingsrud et al…”

Section: Qtaim Bond Properties In Qsarmentioning

confidence: 99%

Modeling biophysical and biological properties from the characteristics of the molecular electron density, electron localization and delocalization matrices, and the electrostatic potential

2014

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The electron density and the electrostatic potential are fundamentally related to the molecular hamiltonian, and hence are the ultimate source of all properties in the ground- and excited-states. The advantages of using molecular descriptors derived from these fundamental scalar fields, both accessible from theory and from experiment, in the formulation of quantitative structure-to-activity and structure-to-property relationships, collectively abbreviated as QSAR, are discussed. A few such descriptors encode for a wide variety of properties including, for example, electronic transition energies, pKa's, rates of ester hydrolysis, NMR chemical shifts, DNA dimers binding energies, π-stacking energies, toxicological indices, cytotoxicities, hepatotoxicities, carcinogenicities, partial molar volumes, partition coefficients (log P), hydrogen bond donor capacities, enzyme–substrate complementarities, bioisosterism, and regularities in the genetic code. Electronic fingerprinting from the topological analysis of the electron density is shown to be comparable and possibly superior to Hammett constants and can be used in conjunction with traditional bulk and liposolubility descriptors to accurately predict biological activities. A new class of descriptors obtained from the quantum theory of atoms in molecules' (QTAIM) localization and delocalization indices and bond properties, cast in matrix format, is shown to quantify transferability and molecular similarity meaningfully. Properties such as “interacting quantum atoms (IQA)” energies which are expressible into an interaction matrix of two body terms (and diagonal one body “self” terms, as IQA energies) can be used in the same manner. The proposed QSAR-type studies based on similarity distances derived from such matrix representatives of molecular structure necessitate extensive investigation before their utility is unequivocally established. © 2014 The Author and the Journal of Computational Chemistry Published by Wiley Periodicals, Inc.

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“…Furthermore, structural patterns of HBs can be smeared by factors such as steric hindrance 8 , packing forces 26 , or be biased by the refinement programs used (which often include specific constraints for HB) 27 . Quantum mechanics (QM) calculations, while requiring more resources than statistical surveys, have been used to characterize various HB properties 26,[28][29][30][31][32][33][34][35] , usually with good agreement with observations 13 . Among them, very few calculated interaction energies at non-equilibrium geometries (the ones that did are summarized in Supplementary Table S1).…”

Section: Introductionmentioning

confidence: 99%

Charting Hydrogen Bond Anisotropy

Santos-Martins¹,

Forli

2019

Preprint

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Hydrogen bond (HB) is an essential interaction in countless phenomena, and regulates the chemistry of life. HBs are characterized by two main features, strength and directionality, with a high degree of heterogeneity across different chemical groups. These characteristics are dependent on the electronic configuration of the atoms involved in the interaction, which, in turn, is influenced strongly by the molecular environment where they are found. Studies based on the analysis of HB in solid phase, such as X-ray crystallography, suffer from significant biases due to the packing forces. These will tend to better describe strong HBs at the expenses of weak ones, which are either distorted or under-represented. Using quantum mechanics (QM), we calculated interaction energies for about a hundred acceptor and donors, in a rigorously defined set of geometries. We performed about 180,000 independent QM calculations, covering all relevant angular components, and mapping strength and directionality in a context free from external biases, with both single-site and cooperative HBs. We show that by quantifying directionality, there is not correlation with strength, and therefore these two components need to be addressed separately. Results demonstrate that there are very strong HB acceptors (e.g., DMSO) with nearly isotropic interactions, and weak ones (e.g., thioacetone) with a sharp directional profile. Similarly, groups can have comparable directional propensity, but be very distant in the strength spectrum (e.g., thioacetone and pyridine). These findings have implications for biophysics and molecular recognition, providing new insight for chemical biology, protein engineering, and drug design. The results require rethinking the way directionality is described, with implications for the thermodynamics of HB. hydrogen bond | drug design | force field | non-covalent interaction Correspondence: forli@scripps.edu ResultsThe dataset contains 34 donors ( Fig.S1) and 67 acceptors ( Fig.S2, Methods). For the entire dataset, calculations were performed using B3LYP density functional with the cc-pVDZ basis set and the counterpoise correction, while MP2/aug-cc-pVTZ with counterpoise correction was used for smaller subsets of complexes. The validation of these two methods, their differences and their effect on the results has been discussed in Supplementary Methods. Strength.We measured the strength of HBs on the 34 donors ( Fig.S1) and 67 acceptors, performing B3LYP/cc-pVDZ calculations of donor-acceptor dimers interacting in optimal ge-July 5, 2019 | 1-20

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Theoretical Prediction of Hydrogen-Bond Basicity pK_BHXUsing Quantum Chemical Topology Descriptors

Cited by 34 publications

References 55 publications

Individual Hydrogen‐Bond Strength QSPR Modelling with ISIDA Local Descriptors: a Step Towards Polyfunctional Molecules

Individual Hydrogen‐Bond Strength QSPR Modelling with ISIDA Local Descriptors: a Step Towards Polyfunctional Molecules

Modeling biophysical and biological properties from the characteristics of the molecular electron density, electron localization and delocalization matrices, and the electrostatic potential

Charting Hydrogen Bond Anisotropy

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Theoretical Prediction of Hydrogen-Bond Basicity pKBHXUsing Quantum Chemical Topology Descriptors

Cited by 34 publications

References 55 publications

Individual Hydrogen‐Bond Strength QSPR Modelling with ISIDA Local Descriptors: a Step Towards Polyfunctional Molecules

Individual Hydrogen‐Bond Strength QSPR Modelling with ISIDA Local Descriptors: a Step Towards Polyfunctional Molecules

Modeling biophysical and biological properties from the characteristics of the molecular electron density, electron localization and delocalization matrices, and the electrostatic potential

Charting Hydrogen Bond Anisotropy

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Theoretical Prediction of Hydrogen-Bond Basicity pK_BHXUsing Quantum Chemical Topology Descriptors