Hydrophobic similarity between molecules: a MST-based hydrophobic similarity index

A similarity index based on the hydrophilic/hydrophobic properties of molecules is presented. Such an index is defined based on the fractional partition of the free energy of solvation developed within the framework of the self-consistent reaction field MST model, which divides the free energy of solvation or the free energy of transfer into contributions assigned to the surface elements defining the solute/solvent interface. These surface contributions can be integrated to derive atomic or group contributions. The suitability of the index to compute the molecular similarity based on hydrophobic/hydrophilic properties is examined by considering their application in a variety of test systems, including structure-activity relationships, absorption properties, and molecular recognition. The similarity index is expected to be a very powerful tool in molecular similarity studies for compounds of chemical, biochemical, and pharmaceutical interest.     

From Wiener index to molecules

In this paper we present an algorithm for the generation of molecular graphs with a given value of the Wiener index. The high number of graphs for a given value of the Wiener index is reduced thanks to the application of a set of heuristics taking into account the structural characteristics of the molecules. The selection of parameters as the interval of values for the Wiener index, the diversity and occurrence of atoms and bonds, the size and number of cycles, and the presence of structural patterns guide the processing of the heuristics generating molecular graphs with a considerable saving in computational cost. The modularity in the design of the algorithm allows it to be used as a pattern for the development of other algorithms based on different topological invariants, which allow for its use in areas of interest, say as involving combinatorial databases and screening in chemical databases.     

A generalized expression for the similarity of spectra: application to powder diffraction pattern classification

A generalized expression is given for the similarity of spectra, based on the normalized integral of a weighted crosscorrelation function. It is shown that various similarity and dissimilarity criteria previously described in literature can be written as special cases of this general expression. A new similarity criterion, based on this generalized expression, is introduced. The benefits of this criterion are that it properly recognizes shifted but otherwise similar details in spectra and that the resulting similarity measure is normalized. Moreover, the criterion can easily be adapted to specific properties of spectra resulting from various analytical methods. The new criterion is applied to the classification of a series of crystal structures of cephalosporin complexes, based on comparison of their calculated powder diffraction patterns. The results are compared with those obtained using previously described criteria. © 2001 John Wiley & Sons, Inc. J Comput Chem 22: 273–289, 2001     

From primary structure to function: biological insights from large-molecule mass spectra

As increasing information is available from genomic databases, mass spectrometry has begun to be used to identify and/or assess regions of predicted DNA or protein sequence. Mass spectrometry performance limits, together with experiments designed for genomic interplay, are being extended to allow accurate genotyping and protein profiling of cells at rates commensurate with the data-intensive future of biology.     

Software-based mass spectral enhancement to remove interferences from spectra of unknowns

Gas chromatography-mass spectrometry data from the analysis of complex environmental samples were converted into ASCII text and imported into a personal computer spreadsheet. A macro was written to perform mass spectral enhancement by statistical and mathematical procedures to separate the spectra of compounds of interest from interfering mass spectral responses, such as those of broadly eluting hydrocarbons. The extracted mass spectra were compared to reference spectra, with the result that usually 80–90% of the ions common to those in the reference spectra were successfully extracted by using this method. This procedure improved mass spectral quality and the ability of the data system to perform successful library searches. The fitted quality parameters showed systematic improvements after the data were subjected to the spectral enhancement procedures. These procedures could help to identify unknowns by separating their spectra from other signals, such as those of background aliphatic hydrocarbons.     

Automatic analysis of mixed spectra : Generalised spectral subtraction applied to electron spin resonance spectroscopy

A new technique is described for estimating the pure component spectra from a set of linearly independent spectra. The process is one of generalised spectral subtraction in which an iterative combination of multivariate linear least-squares analysis and matrix transformation is applied to the input data to give estimates of the number of independent components in the original mixed spectra. This technique is applicable to bipolar data (e.g. from e.p.r. spectra) as well as absorption spectra determined by any spectroscopic technique, provided that the spectra may be reasonably assumed to be an additive mixture of unknown pure components. Numerical model examples are given together with an experimental application to electron spin resonance.     

From substrate disorder to contact angle hysteresis, and back

Based on Monte Carlo simulation of the contact line as a long-range elastic model, we develop tools relating substrate traps, trapping time and trapping length. We demonstrate the possibility of retrieving some information on the substrate topography from measurements of contact line motion, near the threshold in forced spreading or near the advancing angle in spontaneous spreading.     

Molecular similarity for small species: refining the isoelectronic index.

This paper tests a chemical-similarity model against properties of gas-phase neutral triatomic and four-atom molecules. The model is a variant of the Diatomics-in-Molecules (DIM) picture, which considers a molecule to be the superposition of all diatomic molecules that could be formed from adjacent atoms in the molecule. The variant is that adjacent atoms are counted as a diatomic molecule only if they are bonded. The tests consist of investigating whether molecules with the same number of electrons, computed by the adjacent-DIM model, have data more similar than do molecules selected at random. The tests vindicate the model for the heat of atomization and for the equilibrium constant for formation, they agree with the model with lesser confidence for the entropy and the partition function, and they show that the model fails for the ionization potential. The model applies with most confidence to molecules with the more electronegative atoms from rows 2 or 3 (those of greatest interest in organic chemistry) and with lesser confidence otherwise. For these properties and these molecules, the model passes graphical and statistical tests at least as well as does the traditional isoelectronic model. Thus, this work refines what may be called the isoelectronic index.     

Using switched angle spinning to simplify NMR spectra of strongly oriented samples

This contribution describes a method that manipulates the alignment director of a liquid crystalline sample to obtain anisotropic magnetic interaction parameters, such as dipolar coupling, in an oriented liquid crystalline sample. By changing the axis of rotation with respect to the applied magnetic field in a spinning liquid crystalline sample, the dipolar couplings present in a normally complex strong coupling spectrum are scaled to a simple weak coupling spectrum. This simplified weak coupling spectrum is then correlated with the isotropic chemical shift in a switched angle spinning (SAS) two-dimensional (2D) experiment. This dipolar-isotropic 2D correlation was also observed for the case where the couplings are scaled to a degree where the spectrum approaches strong coupling. The SAS 2D correlation of C(6)F(5)Cl in the nematic liquid crystal I52 was obtained by first evolving at an angle close to the magic angle (54.7 degrees ) and then directly detecting at the magic angle. The SAS method provides a 2D correlation where the weak coupling pairs are revealed as cross-peaks in the indirect dimension separated by the isotropic chemical shifts in the direct dimension. Additionally, by using a more complex SAS method which involves three changes of the spinning axis, the solidlike spinning sideband patterns were correlated with the isotropic chemical shifts in a 2D experiment. These techniques are expected to enhance the interpretation and assignment of anisotropic magnetic interactions including dipolar couplings for molecules dissolved in oriented liquid crystalline phases.     

From theory of spectra to standardless analysis of molecular objects

The authors discuss the methodology of quantitative analysis of pure substances and mixtures by optical spectra (IR, Raman, UV, etc.) without using samples of standard composition (standardless molecular spectral analysis). An algorithm of quantitative mixture analysis using the reduction of ideal spectra to real ones and computational algorithms of the determination of component concentrations in a mixture taking into account error distribution is proposed. The applicability of the method is estimated using computational experiments parsed and conclusions about the specific features of its work are drawn.     

On generalized Borgen plots. I: From convex to affine combinations and applications to spectral dataSpectra

In 1985, Borgen and Kowalski (Anal. Chim. Acta 1985; 174 : 1‐26) published their landmark paper on the geometric construction of feasible regions for nonnegative factorizations of spectral data matrices for three‐component systems. These geometric constructions are called Borgen plots. Borgen plots are principally restricted to nonnegative data and are sometimes considered as analytical tool. Major contributions to this theory have been given by Rajkó. In contrast to these geometric constructions, numerical methods to compute the so‐called area of feasible solutions (AFS) have been studied by Golshan et al. (Anal. Chem. 2011; 83 (3): 836‐841) and by Sawall et al. (J. Chemom. 2013; 27 : 106‐116). These numerical methods can even treat spectral data, which include slightly negative components. In this work, the concept of generalized Borgen plots is introduced for spectral data, which are polluted by small negative entries. The analysis is not restricted to three‐component systems but can be applied to general s‐component systems. Generalized Borgen plots are identical to the classical Borgen plots for nonnegative data. The analysis in this work also bridges the gap between the different scalings (Borgen norms) used for AFS computations. The algorithmic procedure of generalized Borgen plots for three‐component systems and its implementation in the FAC‐PACK software are described in the second part of this paper. Copyright © 2015 John Wiley & Sons, Ltd.     

From C58 to C62 and back: Stability,structural similarity,and ring current

An increasing number of observations show that non‐classical isomers may play an important role in the formation of fullerenes and their exo‐ and endo‐derivatives. A quantum‐mechanical study of all classical isomers of C₅₈, C₆₀, and C₆₂, and all non‐classical isomers with at most one square or heptagonal face, was carried out. Calculations at the B3LYP/6‐31G* level show that the favored isomers of C₅₈, C₆₀, and C₆₂ have closely related structures and suggest plausible inter‐conversion and growth pathways among low‐energy isomers. Similarity of the favored structures is reinforced by comparison of calculated ring currents induced on faces of these polyhedral cages by radial external magnetic fields, implying patterns of magnetic response similar to those of the stable, isolated‐pentagon C₆₀ molecule. © 2016 Wiley Periodicals, Inc.     

Correlating the vibrational spectra of structurally related molecules: A spectroscopic measure of similarity

Using catastrophe theory and the concept of a mutation path, an algorithm is developed that leads to the direct correlation of the normal vibrational modes of two structurally related molecules. The mutation path is defined by weighted incremental changes in mass and geometry of the molecules in question, which are successively applied to mutate a molecule into a structurally related molecule and thus continuously converting their normal vibrational spectra from one into the other. Correlation diagrams are generated that accurately relate the normal vibrational modes to each other by utilizing mode‐mode overlap criteria and resolving allowed and avoided crossings of vibrational eigenstates. The limitations of normal mode correlation, however, foster the correlation of local vibrational modes, which offer a novel vibrational measure of similarity. It will be shown how this will open new avenues for chemical studies. © 2017 Wiley Periodicals, Inc.     

Extending molecular similarity to energy surfaces: Boltzmann similarity measures and indices

Maxwell-Boltzmann statistics provides the adequate mathematical background allowing to define similarity measures involving molecular energy surfaces and electrostatic potential maps. Boltzmann similarity measures are described and various illustrative examples are used to show the practical viability of the theory. A new molecular similarity index is also presented. Finally, hybrid measures involving Boltzmann and density distributions are defined.     

How similar is a molecule to another? An electron density measure of similarity between two molecular structures

A matching measure between two molecular structures based on density functions is described. Some examples related with an alarm pheromone activity are given; the results encourage the possible use of similarity density concepts in molecular engineering.     

Linear scaling approaches to quantum macromolecular similarity: evaluating the similarity function

The evaluation of the electron density based similarity function scales quadratically with respect to the size of the molecules for simplified, atomic shell densities. Due to the exponential decay of the function's atom-atom terms most interatomic contributions are numerically negligible on large systems. An improved algorithm for the evaluation of the Quantum Molecular Similarity function is presented. This procedure identifies all non-negligible terms without computing unnecessary interatomic squared distances, thus effectively turning to linear scaling the similarity evaluation. Presented also is a minimalist dynamic electron density model. Approximate, single shell densities together with the proposed algorithm facilitate fast electron density based alignments on macromolecules.     

Molecular similarity of potential endocrine disruptors: Structural index control of pharmacological clustering

A series of 37 substituted indoles for which estrogen receptor binding data had been reported were studied from a quantitative structure–activity relationship (QSAR) viewpoint. The structures were represented by an established unitary mathematical index, the molecular transform (FT_m), whose derivation is entirely from the geometry‐optimized structure. Data clusters were generated by a primary numerically descending sort of the structure indices and a concurrent secondary numerically descending sort of the binding data. Reversal of numerical descent of the latter served to generate the cluster boundaries. Analysis within and across the clusters permitted a definitive and detailed picture of the influence of substituents and substituent positions on the molecule, and their effect on the biodata, and suggested the structure of a molecule of greater binding ability than any in the database. The relationship of the electronic and charge nature of the molecules to their binding ability was considered. © 2003 Wiley Periodicals, Inc. Int J Quantum Chem, 2003