Molecular Engineering: A General Approach to QSAR

Carbó, Ramon; Arnau, C.

doi:10.1016/b978-0-08-025297-1.50012-x

Cited by 9 publications

(5 citation statements)

References 24 publications

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“…In this context, besides the computational methodology advances which have made possible a more rigorous basis for interpretation, the approaches to a quantum-chemical analysis of molecular similarity, suitable for numerically evaluating even small variations in intramolecular effects, have provided an important framework. [6][7][8][9][10][11][12][13][14][15][16][17] These methods have allowed a detailed, quantum chemistry based comparison of various effects of substituents within molecules, as manifested in the changes in the structures and electron distributions of molecules. The actual intramolecular effects of substituents can be monitored by investigating and using numerical measures to evaluate molecular similarities, hence the differences induced by substituent effects.…”

Section: Introductionmentioning

confidence: 99%

Substituent effects and local molecular shape correlations

Antal

Mezey

2014

Phys. Chem. Chem. Phys.

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Using a detailed electron density shape analysis methodology, a new method is proposed for studying the main components of substituent effects in a series of disubstituted benzenes, in correlation with their activating and deactivating characteristics as observed by the induced shape changes of a local electron density cloud. The numerical measures obtained for the extent of shape changes can be correlated with known and with some unexpected effects of various substituents. The insight obtained from the shape analysis provides a theoretical, electron density based justification for some well-known trends, but it also provides new explanations for some of the unexpected features of these substituent effects.

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Section: Introductionmentioning

confidence: 99%

Substituent effects and local molecular shape correlations

Antal

Mezey

2014

Phys. Chem. Chem. Phys.

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“…By overlaying the two (a, b) parameter maps and assigning a value of 1 to each position (a, b) in the map where the two shape integers L(K, a, b) and L(K', a, b) match, and a value of 0 where the two shape integers are different, a binary map is generated that provides an overview of similarity between the two molecular electron densities. A total similarity measure is then given as [41 Xi , j ) = 1 1 A(i, j, a,, b 0 I ( N , Nb) V=l where N, and N , are the number of thresholds for the a and b values, respectively, and Using this procedure, the shape features of the two electron densities can be compared by an algorithmic technique based on detailed shape analysis, providing a method that complements the quantum similarity approaches of Carb6 et al (27)(28)(29)(30)(31)(32)(33)(34)(35) and alternative techniques proposed earlier (36)(37)(38)(39)(40)(41)(42)(43)(44)(45)(46)(47)(48)(49)(50).…”

Section: A Brief Review Of the Shape Group Methodsmentioning

confidence: 99%

Shape-similarity analysis of 20 stable conformations of neutral β-alanine

Heal¹,

Walker²,

Ramek³

et al. 1996

Can. J. Chem.

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Abstract:The family of 20 stable conformations of neutral p-alanine are analyzed in terms of their shape similarities using the topological Shape Group Method, a general molecular shape analysis technique as applied to the three-dimensional electronic density. Molecular electron densities are calculated using the 6-3 IG*" basis set, followed by the determination of the shape groups of local curvature patterns for the entire chemically relevant range of electron density contour surfaces. The results of the shape group analysis are represented by two-dimensional shape maps. Discretized grids of these maps generate numerical shape codes, and comparisons of these numerical codes serve as measures of shape similarity of the various conformers of 0-alanine. This technique is based on direct comparisons of the intrinsic shape features of molecules and requires no superposition of molecules for comparisons. Mathematically well-defined and unbiased similarity measures are obtained by this non-visual, computer-based method, useful for the detection, quantification, and analysis of electronic charge distribution similarities. The family of 20 stable conformers of p-alanine serves as a test case for the application of the methodology for a large number of conformers, representing a level of complexity analogous to that of typical conformational problems in computer-aided drug design and the screening of potential drug molecules for shape similarity.Key words: similarity measures, shape groups, p-alanine, conformation analysis, molecular shape, electron density.RCsumC : On a analysk la famille de 20 conformations stables de la p-alanine neutre en fonction des similitudes de leur forme, en utilisant la Mkthode de groupe de forme topologique. On a appliquk la technique d'analyse de la forme moltculaire gknerale h la densitk klectronique en trois dimensions. On a calcult les densitts moltculaires klectroniques en utilisant l'ensemble de base 6-3 IG**, suivi d'une dktermination des groupes de forme du modele de courbure locale pour tout le domaine chimiquement caractkristique des surfaces de contour de la densit6 Clectronique. On reprksente les rksultats de l'analyse des groupes de forme par des diagrammes de forme en deux dimensions. Des grilles discontinues de ces diagrammes gknbrent des codes de forme numkrique et les comparaisons de ces codes numtriques servent de mesure de la similitude de forme des divers conformeres de la 0-alanine. Cette technique est baske sur la comparaison directe des caractkristiques de formes intrinsbques des moltcules et ne requiert pas, pour les comparaisons, la superposition des molecules. On a obtenu des mesures de similitude bien dtfinies mathkmatiquement et sans influence par cette methode non visuelle baske sur ordinateur, utile pour la dktection, la quantification et l'analyse des similitudes de distribution de la charge tlectronique. La famille des 20 conformbres stables de la 0-alanine sert de cas type pour I'application de la mtthodologie h un plus grand nombre de conformbres, reprksentan...

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“…On the other hand, among the early theoretical studies on the relevant aspects of molecular similarity, the works based on the original quantum similarity approach of Carbo has played a central role. [11][12][13][14][15][16][17][18][19][20][21] It has been clear early that the electron density cloud plays a central role in transmitting the influence of substituents within a molecule, also confirmed by the fundamental theorem of density functional theory, the Hohenberg-Kohn theorem: 22 the non-degenerate ground state electron density contains the complete molecular information.…”

Section: Introductionmentioning

confidence: 99%

“…Also motivated by the successes of molecular similarity studies, [11][12][13][14][15][16][17][18][19][20][21] the interest in a better understanding of the details of through-space and through-bond influences has remained strong, with the ultimate aim of being able to utilize the potential influence of well-selected substituents in order to achieve a desired chemical effect.…”

Section: Introductionmentioning

confidence: 99%

“…The approach employed here is in part motivated by Carbo's quantum self-similarity measures, (QS-SM), [11][12][13][14][15][16][17][18][19][20][21] linking density functional theory with some more traditional approaches. This approach is based on a theory using electron density as the ultimate molecular descriptor and, as a part of it, fragment QS-SM to describe electronic substituent effects in the molecule.…”

Section: Introductionmentioning

confidence: 99%

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Electron density shape analysis of a family of through-space and through-bond interactions

Antal

Warburton

Mezey

2014

Phys. Chem. Chem. Phys.

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A family of styrene derivatives has been used to study the effects of through-space and through-bond interactions on the local and global shapes of electron densities of complete molecules and a set of substituents on their central rings. Shape analysis methods which have been used extensively in the past for the study of molecular property-molecular shape correlations have shown that in these molecules a complementary role is played by the through-space and through-bond interactions. For each specific example, the dominance of either one of the two interactions can be identified and interpreted in terms of local shapes and the typical reactivities of the various substituents. Three levels of quantum chemical computational methods have been applied for these structures, including the B3LYP/cc-pVTZ level of density functional methodology, and the essential conclusions are the same for all three levels. The general approach is suggested as a tool for the identification of specific interaction types which are able to modify molecular electron densities. By separately influencing the through-space and through-bond components using polar groups and groups capable of conjugation, some fine-tuning of the overall effects becomes possible. The method described may contribute to an improved understanding and control of molecular properties involving complex interactions with a possible role in the emerging field of molecular design.

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Molecular Engineering: A General Approach to QSAR

Cited by 9 publications

References 24 publications

Substituent effects and local molecular shape correlations

Substituent effects and local molecular shape correlations

Shape-similarity analysis of 20 stable conformations of neutral β-alanine

Electron density shape analysis of a family of through-space and through-bond interactions

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