Theoretical characterization and biological activity investigation of indirubins, cyclin dependent kinases inhibitors.

Up to now, significant research efforts have been directed towards investigating indirubin and its derivatives as potential candidates for developing new compounds with multiple biological activities. In the present work, natural indirubin and numerous of its chemical derivatives referred to as indirubins have been investigated computationally using DFT method with the B3LYP/6-311 + G(d,p) level of theory, in order to reveal structure- biological activity relationship. We started with a structural properties description. Results analysis indicated that extra interaction sites were provided through the set of substitutions in compounds (1): Indirubin-3'-monoxime, (2): Indirubin-5-sulfonic acid, (3): 5-Nitro-indirubinoxime, (4): 5'-OH-5-nitro-indirubinoxime (AGM130), (5): 7-Bromo-5'-carboxyindirubin-3'-oxime, and (6): 7 BIO and consequently, extra hydrogen bonds may be formed with the active sites of molecular targets, such as GSK-3, CDKs, and Aurora kinases, as well as the aryl hydrocarbon receptor. Subsequently, to get more information on the electronic properties of indirubin and its analogues, HOMO, LUMO, Egap, and further electronic parameters were carried out. The indirubin derivatives showed an easier interaction with its environment than indirubin, the parent compound. The UV-Visible spectra of indirubin and compounds 1-6 were also produced using TD-DFT with B3LYP functional and 6-311 + G(2d,p) basis set. The relationship between absorption and chemical structure is discussed. Two phototoxic brominated compounds showed important absorption spectra modifications. It was also found that the main absorption bands of all compounds derived from π→π*(HOMO→LUMO) transitions.Communicated by Ramaswamy H. Sarma.

Rationalizing Aggregate Structures with Orbital Contributions to the Exchange-Repulsion Energy.

It is shown that repulsive interactions have a crucial influence on the structure of prototypical non-covalently bonded systems. To explain this, we propose a molecular orbital-based model for the exchange-repulsion contribution to the total interaction energy. As a central result, our model shows that energetically preferred aggregate structures frequently exhibit reduced exchange repulsion, which can be deduced from the nodal structure of certain occupied orbitals. This is used to explain key features of the intermolecular potentials of the Cl2 -He, benzene-benzene, and benzene-hexafluorobenzene aggregates, which are not correctly reproduced by commonly applied electrostatic models.

DFT evaluation of structural, electronic and variation properties for complex carbohydrates with biological interest.

The synthetic bicyclic bis(hemiacetals) compounds 1,5-pyranose-9,7-pyranoses, with a structural analogy to the bicyclic monosaccharide Bradyrhizose, have been described here based on a theoretical approach, using DFT calculations with the B3LYP functional combined with the 6-311 + G(d,p) basis set. First, we have performed a geometrical and electronic properties description of (1 R,9S), (1S,9S) and (1S,9R)-1,5-pyranose-9,7-pyranoses. Results analysis indicated that, slight differences in the three-dimensional orientations of their atoms lead to an enormous difference in chemical reactivity. Consequently, (1S,9S) and (1S,9R) isomers are predicted to be the most resembling the natural bradyrhizose in structural features. To enhance the performance of these two isomers, a set of modifications through functional groups attached to the reactive sites were determined by local reactivity descriptors. Subsequently, in order to get more information on the obtained derivatives for both isomers, HOMO, LUMO, Egap and four electronic parameters were calculated and compared. The substituted systems show a good performance in chemical reactivity than the unmodified parent compounds.Communicated by Ramaswamy H. Sarma.

Theoretical Study on Non-Linear Optics Properties of Polycyclic Aromatic Hydrocarbons and the Effect of Their Intercalation with Carbon Nanotubes.

Results of a theoretical study devoted to comparing NLO (non-linear optics) responses of derivatives of tetracene, isochrysene, and pyrene are reported. The static hyperpolarizability ß, the dipole moment µ, the HOMO and LUMO orbitals, and their energy gap were calculated using the CAM-B3LYP density functional combined with the cc-pVDZ basis set. The para-disubstituted NO2-tetracene-N(CH3)2 has the highest NLO response, which is related to a large intramolecular charge transfer. Adding vinyl groups to the para-disubstituted NO2-tetracene-N(CH3)2 results in an increase in the NLO responses. We further investigated the effect of the intercalation of various push-pull molecules inside an armchair single-walled carbon nanotube. The intercalation leads to increased NLO responses, something that depends critically on the position of the guest molecule and/or on functionalization of the nanotube by donor and attractor groups.

Testing the CP-correction procedure with different DFT methods on H-bonding complexes of κ-carrabiose with water molecules.

Interaction of water molecules with κ-carrabiose disaccharide, within three H-bonding complexes, was investigated. Particular interest was focused on the way with which the BSSE correction has to be performed. Two strategies were used, either performing BSSE correction during or after optimization. For this aim, several DFT-functionals (hybrid GGA and hybrid meta-GGA) and 6-31 + G* basis set were considered. The results demonstrated the uselessness of including of BSSE-CP correction during optimization for all complexes. From a structural point of view, a proper H-bonding description was obtained using the PBE0 functional for all complexes. The basis set effect on the BSSE using B3LYP functional was also investigated. The reliability of B3LYP/6-31 + G** and B3LYP/6-31++G** models for the complexes involving one or two water molecules was reported while the use of B3LYP/6-311 + G** or B3LYP/6-311++G** levels was shown to be more appropriate for larger complexes equivalent to that involving three water molecules. CP-corrected interaction energies were demonstrated to be closer to CBS-4 M interaction energies than the uncorrected ones. Graphical abstract Functional and basis set effects on BSSE.

Vibrational normal modes calculation in the crystalline state of methylated monosaccharides: Anomers of the methyl-D-glucopyranoside and methyl-D-xylopyranoside molecules.

A structural investigation of the organic molecules is being carried out using vibrational spectroscopy. In this study, normal co-ordinate calculations of anomers of the methyl-D-glucopyranoside and methyl-ß-D-xylopyranoside in the crystalline state have been performed using the modified Urey-Bradley-Shimanouchi force field (mUBSFF) combined with an intermolecular potential energy function. The latter includes Van der Waals interactions, electrostatic terms, and explicit hydrogen bond functions. The vibrational spectra of the compounds recorded in the crystalline state, in the 4000-500 cm(-1) spectral region for the IR spectra, and in the 4000-20 cm(-1) spectral range for the Raman spectra are presented. After their careful examination, several differences in the intensities and frequency shifts have been observed. The theoretical spectra have been obtained after a tedious refinement of the force constants. Thus, on the basis of the obtained potential distribution, each observed band in IR and in Raman has been assigned to a vibrational mode. The obtained results are indeed in agreement with those observed experimentally and thus confirm the previous assignments made for the methyl-α and ß-D-glucopyranoside, as well as for the methyl-ß-D-xylopyranoside.

Density functional conformational study of 2-O-sulfated 3,6 anhydro-α-D-galactose and of neo-κ- and ι-carrabiose molecules in gas phase and water.

We examined the conformational preferences of the 2-O-sulfated-3,6-α-D-anhydrogalactose (compound I) and two 1,3 linked disaccharides constituting-κ or ι-carrageenans using density functional and ab initio methods in gas phase and aqueous solution. Systematic modifications of two torsion angles leading to 324 and 144 starting geometries for the compound I and each disaccharide were used to generate adiabatic maps using B3LYP/6-31G(d). The lower energy conformers were then fully optimized using B3LYP, B3PW91 and MP2 with several basis sets. Overall, we discuss the impact of full relaxation on the energy and structure of the dominant conformations, present the performance comparison with previous molecular mechanics calculations if available, and determine whether our results are impacted, when polarization and diffuse functions are added to the 6-31G(d) basis set, or when the MP2 level of theory is used.