In this work we study the supramolecular interactions between fluorescent dyes of the family of aminocoumarins and a protein which is the main responsible for matter transport in blood, the serum albumin. The experimental data obtained by fluorescent titrations are analysed using Principal Components Global Analysis to obtain the equilibrium binding constants and the fluorescence spectra of the dyes bound to the protein. The results obtained for the different aminocoumarins are then compared.

The circular dichroism spectra of the four possible configurations [(R,R), (R,S), (S,R), (S,S)] of loliolides are simulated on the basis of electronic excitation energies (wavelength) and rotational strengths R (nm) calculated by time dependent density functional theory using three density functionals (B3PW91 , PBE0 , B3LYP) and three basis sets [TZVP, SVP, 6-31G (d)]. All three basis sets give almost similar l and R with B3PW91 and B3LYP methods but with the PBE0 method, lower values of l and R were observed.

A QSAR approach on a dataset of 546 inhibitors of telomerase activity, by interaction with G-quadruplex DNA, was carried out using 2D autocorrelation descriptors. A linear discriminant analysis (LDA) was made on a training set of 437 compounds and it was assessed with 109 compounds belongs to the test set. The model good classified the 80.09% of the dataset and the percentage of good prediction was 78.89%. Only 5 compounds were not classified. The 2D autocorrelation descriptors are able to explain the factors that stabilize the G-quadruplex structure and consequently the inhibition of telomerase by this biological mechanism.

This paper reports a QSAR study for predicting carcinogenic potency of nitroso-compounds bioassayed in female rats administrated by gavage as oral route. Several different theoretical molecular descriptors, - 0D, 1D and 2D - calculated only on the basis of knowledge of the molecular structure and an efficient variable selection procedure, such as Genetic Algorithm, led to models with satisfactory predictive ability. But the best-final QSAR model is based on the combination between; 0D, 1D and 2D-DRAGON descriptors capturing a reasonable interpretation. This QSAR model is able to explain around 86% of the variance in the experimental activity and manifest good predictive ability as indicated by the higher q2s of cross validations, which demonstrate the practical value of the final QSAR model for screening and priority testing. This model can be applied to nitroso-compounds different from the studied nitroso-compounds (even those not yet synthesized) as it is based on theoretical molecular descriptors that might be easily and rapidly calculated.

NICS methodology has been applied to study the change in aromaticity in several aromatic rings (benzene, pyrrol, triazine, hexafluorobenzene) on complexation with several ions (Li+, Na+, K+, F-, Cl-). For this purpose all the isolated and complexed rings have been optimized at the MP2/6-31++G(d,p) level of theory. Using GIAO method to calculate NICS values, the change in aromaticity on complexation was assessed. From the calculated values of NICS(1) and NICS ZZ (1) the only relevant conclusion is that a very small change in aromaticity takes place; however, no trend is observed. Moreover, a large discrepancy between the results from the two aromatic descriptors is found.

Classification algorithms are proposed based on information entropy and applied to 13 human immunodeficiency virus type 1 inhibitors. A number of results are compatible with the data suffering combinatorial explosion. After the equipartition conjecture, entropy production is most uniformly distributed. In ddI the formula is N₄O₃S₀P₀ , X = F, Cl; it is selected as a reference . In most cases (ddI, ddC, d4T, novel proposed ligand) the formula is N_3–4O₃S₀P₀X₀ , while in 3TC the formula is N₃O₃S₁P₀X₀. The analysis compares well with other classification taken as good.

Algorithms for classification and taxonomy based on criteria such as information entropy and its production are proposed. As an example, the feasibility of replacing a given anaesthetic by similar ones in the composition of a complex drug is studied. Some local anaesthetics currently in use are classified using characteristic chemical properties of different portions of their molecules. Many classification algorithms are based on information entropy. When applying the procedures to sets of moderate size, an excessive number of results appear compatible with data, and this number suffers a combinatorial explosion. However, after the equipartition conjecture, one has a selection criterion between different variants resulting from classification between hierarchical trees. According to this conjecture, for a given charge or duty, the best configuration of a flowsheet is the one in which the entropy production is most uniformly distributed. Information entropy and principal component analyses agree.

A method permits semiquantitative estimation of partitioning of solutes between pairs of media. The organic solvent-water partition coefficients P are calculated. For Fe₄S₄Cys_n, the organic solvent–water partition coefficients for 1-octanol P_o, cyclohexane P_ch and chloroform P_cf decrease 4.46, 6.25 and 4.60 per Cys, respectively. P_o are in line with CDHI calculations, and P_ch–cf, with calculations performed with a method by Leo–Hansch. LogP_{o–ch–cf} mean relative errors are –17%, 25% and –17%, which represent mean and unsigned relative errors of –3% and 20%. On varying the number of Cys, the structures show hydrophobic moments indicative of amphipathic structures. For Se substitutions in Fe₄Se₄Cys_nP_{o–ch–cf} decrease 4.52, 6.30 and 4.66 per Cys. With the references P_{o–ch–cf} decrease 4.03, 4.80 and 5.76 per Cys. The similar calculated partition coefficients and hydrophobic moments for Fe₄S_4–mSe_mCys₄ suggest a role of FeSe clusters in physiological processes.

Calculations of traditional HF and DFT based reactivity descriptors are reported for the benzofused thieno[3,2-b]furans in order to get insight into the factors determining the exact nature of its interactions with electrophiles. Global descriptors such as chemical potential, molecular hardness, electrophilicity, frontier molecular orbital energies and shapes, the condensed Fukui functions were determined and used to identify the differences in the stability and reactivity of heterocycles. In general calculated values lead to the conclusion that heterocyclic system in thieno[3,2-b]benzofuran is more aromatic and stable than in isomeric benzothieno[3,2-b]furan. Theoretical results are in complete agreement with the experimental results showing exceptional reactivity of C(2) atom for both isomers. The bond order uniformity analysis, local ionization energy and electrostatic potential energy maps revealed structural and reactivity differences of isomeric thieno[3,2-b]furans. Benzothieno[3,2-b]furan structurally could be analogues with molecule of aromatic benzothiophene substituted with C(2)-C(3) vinylic moiety. Contrary, calculated values for the of thieno[3,2-b]benzofuran shows delocalized p–electron surface that reports stable aromatic system between benzene ring and thiene heterocycle. This evidently point out wherefore the electrophilic substitution reaction for benzothieno[3,2-b]furan goes via addition-elimination mechanism at the C(2) position, and presumes possibility of aromatic electrophilic substitution mechanism scenario for thieno[3,2-b]benzofuran.

The in vitro determination of the permeability through cultured Caco-2 cells is the most often-used in vitro model for drug absorption. In this report, we use the largest data set of measured P_Caco-2, consisting of 157 structurally diverse compounds. Linear discriminant analysis (LDA) was used to obtain quantitative models that discriminate higher absorption compounds from those with moderate-poorer absorption. The best LDA model has an accuracy of 90.58% and 84.21% for training and test set. The percentage of good correlation, in the virtual screening of 241 drugs with the reported values of the percentage of human intestinal absorption (HIA), was greater than 81%. In addition, multiple linear regression models were developed to predict Caco-2 permeability with determination coefficients of 0.71 and 0.72. Our method compares favorably with other approaches implemented in the Dragon software, as well as other methods from the international literature. These results suggest that the proposed method is a good tool for studying the oral absorption of drug candidates.