Ludovic Kurunczi

A review of QSAR for dye affinity for cellulose fibres

Abstract The structure of cellulose fibre is discussed in relation to the relevance of the ligand–receptor concept for dye–fibre binding. An outline of qualitative SAR (structure–activity relationship) for dye–cellulose fibre binding is given, as well as of QSAR/QSPR (quantitative structure–activity/property relationship) for such binding and calculations of pertinent (electronic, geometric and partition) properties of dye molecules. Modern QSAR methods for dye–fibre adsorption include MTD (minimal steric difference) analysis, CoMFA (comparative molecular field analysis), PCRA (principal component regression analysis) and neural network. Series of anthraquinone vat dyes, mono, bisazo and disperse dyes were studied by these methods. Conclusions from these QSAR studies concerning the effect of structural features of dye molecules upon adsorption on cellulose fibres are discussed.

Multiple Linear Regression (MLR) and Neural Network (NN) calculations of some disazo dye adsorption on cellulose

Abstract Multiple Linear Regression (MLR) analysis and Neural Network (NN) calculations are applied to a series of 21 disazo anionic dyes. Three-dimensional Q SAR parameters were derived from the Cartesian coordinates of the dye molecules. Low energy conformations were obtained by molecular mechanics and quantum chemical calculations. Electronic and steric effects in the dye-cellulose binding are present. The proposed MLR models are rough approximations of nonlinear models. Good correlation with the dye affinity from the MLR calculations and a significantly improved fitting of the NN over the MLR models are observed. The model validity was checked for two proposed models derived from different sets of structural parameters by the leave-one-out cross-validation procedure. For the first model, a better validity (‘cross-validated r2’ value, of 0.622) of the NN model is noticed by leaving out one compound (found as outlier) from the training set, in comparison to that of the MLR model obtained for the same set of compounds (q2 = 0.434). The q2 value of a second MLR proposed model is better than that of the corresponding NN model.

A QSAR study of the adsorption by cellulose fibre of anthraquinone vat dyes

Abstract The affinity of a series of 46 anthraquinone vat dyes to cellulose fibre was analysed by multiple regression analysis and the MTD method of QSAR. The main structural feature responsible for fibre binding is the number (n) of bonds of the conjugated chain along the main axis of the molecules (correlation coefficient r = 0.914). Hydrophobic interactions and hydrogen bonding, especially by proton donor groups of the dye molecule are also important (r = 0.943 for a correlation with four structural parameters). The optimized receptor map of the MTD method suggests binding to both crystalline and amorphous regions of the cellulose fibre.

Structure-affinity binding relationships of some 4-aminoazobenzene derivatives for cellulose fibre

Abstract Dye-fibre interactions were modelled for a series of 20 disperse dyes on cellulose fibre by means of the Free-Wilson and MTD (minimum steric difference) methods. Both methods indicate good correlations with dye affinities R = 0·999 and s = 0·317 for the Free-Wilson analysis and R = 0·895, s = 0·939 for the MTD method. The optimized receptor map resulted from the MTD calculations. Substituent contributions to dye affinity from the Free-Wilson analysis suggest the same attractive regions in the dye molecules (and a few steric constraints). The cross-validated r 2 values from the MTD method ( R CVi 2 = 0·432; R CVf 2 = 0·613) indicate a satisfactory predictability of the proposed model.

Lipophilicity in dye-cellulose fibre binding

Abstract Lipophilicity in cellulose dyeing has been modelled by correlations of dye structural parameter with dye affinity and lipophilic dye parameters. In a series of anionic azo dyes hydrophobic interactions in dye-fibre binding only appeared in two subseries of dyes having a coupling component with one or two sulphonic groups. Good correlations with dye affinity and lipophilic paramaters were obtained by the Multiple Linear Regression (MLR) Analysis and Principal-Component-Regression (PCRA) approach. Minimum Steric Difference (MTD) calculations suggest the presence of mainly steric and possible electronic interactions in the adsorption of anionic azo dyes by cellulose fibre. Similar calculations were performed for a series of disperse azo dyes, suggesting possible electronic and hydrophobic effects in dye-fibre binding. Dye lipophilic properties also depend on polarity and bulk terms.

Comparative molecular field analysis (CoMFA), semiempirical (AM1) molecular orbital and multiconformational minimal steric difference (MTD) calculations of anthraquinone dye-fibre affinities

Abstract Comparative molecular field analysis (CoMFA), a three-dimensional quantitative structure-activity approach, was used to interpret the affinity of a series of anthraquinone vat dyes to cellulose fibres. The excellent correlation obtained by this method — even when using a quite small number (five) of components in the partial least-squares analysis (crossvalidated rcv2 = 0.841, conventional r2 = 0.992) — indicates that the dye-fibre interaction is largely dominated by steric and even more important electrostatic effects. Based on the CoMFA field contributions, suggestions for further activity enhancements can be made. Inclusion of molecular orbital (AM1) derived quantitative structure-activity relationship (QSAR) descriptors (ϵHOMO, ϵLUMO and dipole moments μ) does not alter the picture derived from CoMFA fields alone. Of the molecular orbital descriptors, the LUMO orbital energy is found to yield the most important contribution. In addition, a multiconformational minimal steric difference (MTD) analysis, including several low-energy conformations of the investigated compounds, was done. This approach also indicated a good correlation with dye affinity (rcv2 = 0.827, r2 = 0.941). The optimized receptor map is in accordance with the CoMFA electrostatic contour maps.

QSAR studies of disperse azo dyes. Towards the negation of the pharmacophore theory of dye-fiber interaction?

Abstract Twenty-seven disperse azo dyes were analyzed using Quantitative Structure-Activity Relationship (QSAR) methods by correlating variations in the chemical structure with —Δμ °, the affinity to cellulose fiber, Classical QSAR results, r 2 of 0.32 for CLogP (the calculated octanol-water partition coefficient) and r 2 of 0.924 for MTD (minimum topological difference), suggest that steric, but not hydrophobic, effects are important. For Comparative Molecular Field Analysis (CoMFA), a three-dimensional QSAR (3D-QSAR) method, r 2 was 0.925, while q 2 (cross-validated r 2 ) was 0.776 for 2 PCs (principal components). CoMFA results imply that the pharmacophore theory of dye-fiber interaction holds true. However, CoMFA was insensitive to the alignment rules. PCA (Principal Component Analysis) shows that PC1 is related to chemical substituents, whereas PC2 is related to molecular length (λ). The correlation between — Δμ ° and λ (a 1D descriptor) is similar to the CoMFA results. We therefore question the validity of the pharmacophore theory of dye-fiber interaction, and illustrate a case of over fitting in QSAR. Features that could improve disperse azo dye binding to cellulose are proposed.

PLS-DA - Docking Optimized Combined Energetic Terms (PLSDA-DOCET) Protocol: A Brief Evaluation

Docking studies have become popular approaches in drug design, where the binding energy of the ligand in the active site of the protein is estimated by a scoring function. Many promising techniques were developed to enhance the performance of scoring functions including the fusion of multiple scoring functions outcomes into a so-called consensus scoring function. Hereby, we evaluated the target oriented consensus technique using the energetic terms of several scoring functions. The approach was denoted PLSDA-DOCET. Optimization strategies for consensus energetic terms and scoring functions based on ROC metric were compared to classical rigid docking and to ligand-based similarity search methods comprising 2D fingerprints and ROCS. The ROCS results indicate large performance variations depending on the biological target. The AUC-based strategy of PLSDA-DOCET outperformed the other docking approaches regarding simple retrieval and scaffold-hopping. The superior performance of PLSDA-DOCET protocol relative to single and combined scoring functions was validated on an external test set. We found a relative low mean correlation of the ranks of the chemotypes retrieved by the PLSDA-DOCET protocol and all the other methods employed here.

MTD-PLS: a PLS variant of the minimal topologic difference method. III. Mapping interactions between estradiol derivatives and the alpha estrogenic receptor.

A homogeneous collection of 45 estrogen agonist derivatives with relative binding affinities measured to the estrogen receptor from Ratus norvegicus was used. The quantitative structure-activity relationships were derived using an improved minimal topologic difference (MTD) method in a partial least-squares (PLS) variant. The spatially assigned analysis of fragment properties can provide receptor site maps, within the limits of the existing series. A steric misfit was found for the steroidal position 2; benefic hydrophobic and van der Waals (enhanced by high polarizability) interactions were found for the 17alpha-CH=CH-X group. MTD-PLS mapping results are confirmed by the experimentally derived estradiol-estrogen receptor binding site contacts (based on X-ray crystallography). Our results suggest that this MTD-PLS method can yield useful results for interactions with receptors of unknown 3D structure and, generally, for the steric rigidity of receptor sites.

MTD-PLS: A PLS-Based Variant of the MTD Method. A 3D-QSAR Analysis of Receptor Affinities for a Series of Halogenated Dibenzoxin and Biphenyl Derivatives

Abstract MTD-PLS, the Partial Least Squares (PLS) variant of the Minimum Topological Difference (MTD) method is described. In MTD-PLS, molecules are characterised not only by the occupancy or nonoccupancy of the hypermolecular vertices (as in classical MTD), but also by additional descriptors for each vertex: fragmental van der Waals volumes, fragmental hydrophobicities, partial atomic charges, etc. This method was applied to a series of 73 polyhalogenated derivatives of dibenzo-p-dioxine, dibenzofuran and biphenyl (induction of aryl hydrocarbon hydrolase and affinities to rat cytosolic receptor), previously studied by MTD. The separation of steric, hydrophobic, and electrostatic effects was achieved retranslating from the latent variable space into a linear combination of the initial structural variables. The MTD-PLS method yields more detailed results compared to classical MTD, indicating the importance of electrostatic effects at some substituent positions.