Minimum Energy Conformation Research Articles

Combined Experimental and Computational Approach for the Vibrational Characteristics and Theoretical Evaluation of Binding Activities and ADME Descriptors of 2,6-Di-tert-butyl-p-cresol

A crystalline sample of multipotent molecule “2,6-di-tert-butyl-p-cresol” (DBPC) was characterized by FT-IR, FT-Raman and its spectroscopic signatures were analyzed using density functional theory (DFT) computations. The weaker intermolecular interactions such as π-π, alkyl-alkyl, π-alkyl in the extended molecular framework were analyzed by Quantum topological atoms in molecule approach. The conformational analysis of the structure and the optimized geometrical parameters of the minimum energy conformer were discussed in detail. The excitation energies corresponding to one electron transition from various HOMO and LUMO energy levels were predicted using DFT. The second-order perturbation approach has been implemented to determine interaction energies between the molecular species. The predicted nonlinear optical (NLO) properties (second-order hyperpolarizabilities) suggest that DBPC can act as NLO materials. Since it has been already found as an anti-oxidant agent, an attempt was performed to find its active binding sites on phase II metabolism isoenzyme. The adsorption, distribution, metabolism and excretion descriptors were predicted to evaluate its drug-likeness. Also, the Swiss BOİLED-Egg model indicates that DBPC can be passively permeated through the blood-brain barrier and is predicted not to be effluated from the central nervous system by p-glycoprotein (PGP¯).

Ab initio and NBO studies of methyl internal rotation in 1-methyl-2(1H)-quinolinone: effect of aromatic substitution to 1-methyl-2(1H)-pyridone.

1-methyl-2(1H)-quinolinone (MeQone) forms the framework of several hundred alkaloid molecules both natural and synthetic being used for various biological applications. From chemical structure point of view, the molecules can also be seen as an aromatic ring fused to 1-methyl-2(1H)-pyridone (1-MPY). In this work, we present theoretical investigations on internal rotation of methyl group in MeQone in light of 1-MPY. We looked into the change in the three-fold (V3) methyl internal rotation barrier resulted from the aromatic ring substitution to 1-MPY. The V3 term in two molecules were calculated using density functional theory and Hartree-Fock theory with different basis sets. MeQone has calculated V3 term (in S0 state) three times higher in magnitude compared with that of 1-MPY. The role of aromatic substitution in increase of V3 term is investigated using natural bond orbital (NBO) analyses. In the NBO analysis, it is found that the aromatic ring as highly delocalized π-system lowers the magnitude of hyperconjugation energy in MeQone compared with 1-MPY. This is due to the extension of delocalization of π-electrons to pyridone ring which lowers the orbital overlap. However, the Lewis energy increases substantially and make the overall barrier energy higher in MeQone compared with 1-MPY. From our study, we conclude that in the molecules such as 1-MPY and MeQone where the methyl group has two single bonds vicinal to it, the overall hyperconjugation energy is always barrier forming with nonlocal interactions playing significant role. Also, the Lewis energy plays the decisive role in barrier formation, and its magnitude can be tuned by tuning the π-electron delocalization. We have also looked into the change in methyl group conformation upon electronic excitation to S1 state. In 1-MPY, the methyl group rotated by 60° upon excitation whereas in MeQone, there was no conformational change. Strong π*-σ* interaction in LUMO in top-of-barrier conformation is responsible for the change in the methyl group conformation in 1-MPY, whereas same π*-σ* interaction in LUMO of minimum energy conformation results in unchanged excited state conformation in MeQone. Graphical abstract.

Effect of Piedmont mutation (L34V) on the structure, dynamics, and aggregation of Alzheimer’s Aβ40 peptide

The amyloid-β (Aβ) aggregation in the brain has been associated with the development of Alzheimer’s disease (AD). The previous studies have reported that Piedmont mutation (L34V) increases the rate of Aβ40 aggregation. However, the underlying molecular mechanism of the effect of L34V mutation on Aβ40 structure, dynamics, and aggregation remains largely unclear. In the present study, molecular dynamics (MD) simulations were performed to elucidate the effect of L34V mutation on the structural changes and conformational dynamics of Aβ40. The secondary structure analysis highlight that L34V mutation enhances Aβ40 self-assembly due to the formation of aggregation-prone β–sheet structure at the C-terminus of Aβ40 monomeric structure. The higher probability of Asp23–Lys28 salt bridge interaction in Aβ40(L34V) leads to aggregation prone β–sheet conformations, which has the potential to increase the fibril formation rate. The free energy landscape (FEL) analysis depict a sampling of coil conformation in the free energy minima of Aβ40, whereas the aggregation-prone β–sheet conformation was observed at the C-terminal region of Aβ40(L34V) in the minimum energy conformations extracted from FEL of Aβ40(L34V). MD simulations, in agreement with experiment, highlight that L34V mutation increases Aβ40 aggregation as the sampling of the aggregation–prone β–sheet conformation substantially increased. Overall, MD simulations provided atomic level details into the increased fibril formation tendency upon L34V mutation and physical insights into the L34V-mediated conformational as well as structural changes in Aβ40.

Quantum chemical and X-ray diffraction studies of (E)-3-(((3,4-dimethoxybenzyl)imino)methyl)benzene-1,2-diol

In this study, the target compound, (E)-3-(((3,4-dimethoxybenzyl)imino)methyl)benzene-1,2-diol, has been synthesized and characterized by FT-IR, UV–Vis and 1H NMR, 13C NMR methods. It’s molecular structure has been experimentally elucidated by single crystal X–ray diffraction method. As a result of the X–ray diffraction experiment, it was found that the title molecule is in zwitterionic form. The minimum energy conformation in the gas phase of the title compound was achieved by density functional theory (DFT) method with the B3LYP hybrid functional using 6–31G(d,p) basis set. Accordingly, global (HOMO, LUMO, hardness and softness parameters) and local (MEP, FF, net charges) chemical activity descriptors were investigated. The stability of the molecule arising from hyperconjugative interactions, charge delocalization were analyzed by using natural bond orbital analysis (NBO) and nonlinear optical properties were investigated. Also, the interactions between the molecule with DNA bases such as adenine, cytosine, guanine, and thymine were investigated by using the ECT (electrophilicity-based charge transfer) method and ΔN (charge transfer) for investigating the charge transfer, electrophilic and nucleophilic nature.

Enhanced piezoresponse and nonlinear optical properties of fluorinated self-assembled peptide nanotubes

Self-assembled L,L-diphenylalanine (FF) nanostructures offer an attractive platform for photonics and nonlinear optics. The nonlinear optical (NLO) coefficients of FF nanotubes depend on the diameter of the tube [S. Khanra et al. Phys. Chem. Chem. Phys. 19(4), 3084–3093 (2017)]. To further enhance the NLO properties of FF, we search for structural modifications. Here, we report on the synthesis of fluorinated FF dipeptides by replacing one ortho-hydrogen atom in each of the phenyl groups of FF by a fluorine atom. Density-functional theoretical calculations yield insights into minimum energy conformers of fluorinated FF (Fl-FF). Fl-FF self-assembles akin to FF into micron-length tubes. The effects of fluorination are evaluated on the piezoelectric response and nonlinear optical properties. The piezoelectric d15 coefficient of Fl-FF is found to be more than 10 times higher than that of FF nanotubes, and the intensity of second harmonic generation (SHG) polarimetry from individual Fl-FF nanotubes is more than 20 times that of individual FF nanotubes. Furthermore, we obtain SHG images to compare the intensities of FF and Fl-FF tubes. This work demonstrates the potential of fluorine substitution in other self-assembled biomimetic peptides for enhancing nonlinear optical response and piezoelectricity.

Structures of the oxidized states of some common biochemical reducing agents

Abstract The crystal structures of the oxidized states of three of the most common biochemical reducing agents have been determined, by crystallization from aqueous solution where possible: tris(2-carboxyethyl)phosphine oxide (TCEP oxide, 1), bis(2-hydroxyethyl) disulfide (2MESS, 3), and tributylphosphine oxide (Bu4PO, 4). In addition, a less disordered crystal structure of the reducing agent tris(2-carboxyethyl)phosphonium chloride (TCEP·HCl, 2) has been obtained. A greatly simplified method was found for synthesizing 1. An unusual method of obtaining X-ray quality crystals from hard-to-crystallize oily liquids is described, in which the oil is solidified to a glass by rapid cooling, allowed to warm to a supercooled liquid containing a few seed crystals, and finally crystallized just below its melting point. This method was successfully used to crystallize 3, a viscous oil at room temperature that had resisted all other methods of crystallization, for X-ray diffraction. An ab initio quantum chemical analysis of the conformers of 3 showed that the molecular geometry of this flexible molecule in the solid state was 320 kJ/mol higher than that of the lowest-energy conformer, underscoring the fact that the solid-state structure may not always yield the same molecular geometry as that of the minimum-energy conformer, especially for flexible molecules with strong intramolecular nonbonding interactions. The unusual NMR spectral characteristics of 4 are elucidated.

Vibrational and computational analysis for molecular structure properties of N-(2-(trifluoromethyl)phenyl)acetamide: Density functional theory approach

The conformational study using Potential Energy Surface analysis was performed and its minimum energy conformer has been obtained for N-(2-(Trifluoromethyl)phenyl)acetamide. Fourier Transform Infrared and Fourier Transform Raman investigation have been done experimentally and theoretically. Nuclear Magnetic Resonance analysis has been performed to obtain 1H and 1C chemical shifts. Ultraviolet-Visible analysis has been performed to obtain maximum absorption wavelength. The molecular orbital diagram with different energies has been obtained and compared with the band gap of Ultraviolet-Visible data. Wave function analysis has been discussed to know the electronic properties. Thus, this present study reports the structural, electrical, chemical activities of the title compound.

Structural (PES), AIM, spectroscopic profiling (FT-IR, FT-Raman, NMR and UV), HOMO-LUMO and docking studies of 2,2-dimethyl-N-(2-pyridinyl)propanamide – a DFT approach

Abstract The conformational study (PES) has been performed and a minimum energy conformer structure has been chosen for DFT exploration on 2,2-dimethyl-N-(2-pyridinyl)propanamide. AIM topological analysis, FT-IR and FT-Raman investigation have been implemented by emerging DFT calculations based on the B3LYP level with 6-311++G(d,p) basis set, which also helps to provide useful information about the structure of the title compound. NMR has been carried through the same method along with the GIAO method for assigning 1H and 13C chemical shifts. The results were compared and discussed with experimental data. UV–Visible analysis has been done by taking DMSO as a solvent to obtain maximum absorption wavelength. HOMO-LUMO diagram for different energies has been illustrated and compared with UV–Visible data to know the maximum filled and empty frontier orbitals. Charge density distribution and chemical activity region of the molecule have been shown by molecular electrostatic potential (MEP) and contour map. Mulliken atomic charges to know electronegative and electropositive atoms in a molecule, thermodynamic variables at various temperatures were estimated. The molecular docking studies revealed that the title molecule plays an important role in binding proteins to exhibit Glutathione thiolesterase inhibition. Thus, this present study reports the structural, electrical, chemical and biological activities of 2,2-dimethyl-N-(2-pyridinyl)propanamide.

Absolute configuration of phomactatriene diterpenoids obtained by Wagner-Meerwein rearrangement of epimeric verticillols.

The epimeric diterpenes (+)-(1S,3E,7E,11S,12S)-verticilla-3,7-dien-12-ol (1), isolated from Bursera suntui, and (+)-(1S,3E,7E,11S,12R)-verticilla-3,7-dien-12-ol (2), isolated from Bursera kerberi, gave the same Wagner-Meerwein rearrangement product (-)-(1E,4Z,8Z,11S,12R)-phomacta-1,(15)4,8-triene (3). The Et2 O:BF3 -induced transformations evidence that verticillenes and phomactanes, both containing the bicyclo[9.3.1]pentadecane skeleton, are biogenetically related through the verticillen-12-yl cation (A+ ), which also is a key intermediate in the biosynthetic pathways to generate antitumor taxanes. Molecular modeling using the Monte Carlo protocol, followed by density functional theory (DFT) geometry optimization employing the hybrid functionals B3LYP and B3PW91, both with the DGDZVP basis set, secured the configuration of 3 as followed from the good agreement between the calculated and experimental vibrational circular dichroism spectra. Similar DFT calculations allowed determining the absolute configuration of (+)-(1R,4R,5R,8S,9S,11S,12R,15R)-1,15:4,5:8,9-triepoxyphomactane (9), which surprisingly derives from epoxidation of the second minimum energy conformer of 3.

Density functional theory, molecular docking and bioassay studies on (S)-2-hydroxy-N-(2S,3S,4R,E)-1,3,4 trihydroxyicos-16-en-2-yl)tricosanamide

A novel indigoferamide-A, earlier isolated from the seeds of Indigofera heterantha Wall was characterized using density functional theory, molecular docking and bioassays studies. Density functional theory calculations were performed at B3LYP/6-31G(d,p) to gain geometric insight of the compound. Conformational analyses have been performed around three important dihedral angles to explore the lowest energy structure and conformer. The simulated vibrational spectrum of the compound at B3LYP/6-31G(d,p) was scaled with two scaling factors, and the scaled harmonic vibrations shows nice correlation with the experimental values. 1H and 13C NMR chemical shifts were calculated using Cramer's re-parameterized function W04 at 6- 31G(d,p) basis set. Several conformers lying within 2 kcal mol−1 of the minimum energy conformer were considered; however, the chemical shifts were not significantly different among these conformers. The Gaussian averaged theoretical 1H and 13C chemical shifts correlate nicely with the experimental data. Electronic properties such as band gap, ionization potential and electron affinities were also simulated for the first time, however, no comparison could be made with the experiment. The compound was also screened for urease, antiglycation activities and the theoretical explanation of the results is provided based on molecular docking simulations.

Synthesis, Pharmacological, and Biological Evaluation of MIF-1 Picolinoyl Peptidomimetics as Positive Allosteric Modulators of D2R

This work describes the synthesis and pharmacological evaluation of picolinoyl-based peptidomimetics of melanocyte stimulating hormone release inhibiting factor 1 (MIF-1) as dopamine modulating agents. Eight novel peptidomimetics were tested for their ability to enhance the maximal effect of tritiated N-propylapomorphine ([3H]-NPA) at dopamine D2 receptors (D2R). Methyl picolinoyl-l-valyl-l-alaninate (compound 6b) produced a statistically significant increase in the maximal [3H]-NPA response at 0.01 nM (11.9 ± 3.7%), which is close to the effect of MIF-1 in this assay at same concentration (18.3 ± 9.1%). Functional assays measuring cAMP mobilization in the presence of dopamine corroborate the activity of peptidomimetic 6b as a positive allosteric modulator (PAM) of D2R. In this assay, 6b produced a typical bell-shaped dose-response curve similar to that of the parent neuropeptide (18.3 ± 7.1% for 6b vs 15.4 ± 5.5% for MIF-1, both at 0.1 nM). Dose-response curves for dopamine in the presence of 6b show EC50 (0.33 ± 0.21 μM for 6b vs 0.17 ± 0.07 μM for MIF-1) and Emax (86.0 ± 5.4% for 6b vs 93.6 ± 4.4% for MIF-1) comparable to those of MIF-1, both at 0.01 nM. Furthermore, peptidomimetic 6b was tested for agonist activity at the human D2R and the results show that it displays no intrinsic agonism effect, endorsing its activity as a PAM of D2R. Cytotoxic and neurotoxic assays were performed for peptidomimetic 6b using HEK 293T cells and cortex neurons from 19 day old Wistar-Kyoto rat embryos, respectively, suggesting this analogue displays no toxicity effect in these assays up to 100 μM. Conformational energy minimization for 6b shows that this peptidomimetic cannot adopt the postulated type-II β-turn bioactive conformation, endorsing the possibility of an extended bioactive conformation as claimed by other researchers as a second bioactive conformation of MIF-1. Overall, the pharmacological and toxicological profile of peptidomimetic 6b together with its favorable druglike properties and structural simplicity makes it a potential lead compound for further development and optimization.

Improving Ligand Geometry in Protein Data Bank Structures Computationally

Information about the three‐dimensional structures of complex biological molecules is an indispensable research tool for many fields of study, including biology, chemistry, pharmacology, and computer science. The Protein Data Bank (PDB) is an public digital archive providing access to structures of nucleic acids, proteins, and large macromolecular machines determined experimentally by X‐ray crystallography, nuclear magnetic resonance (NMR) spectroscopy, and 3‐dimensional electron microscopy (3DEM). PDB structures undergo validation for structural plausibility upon their deposition into the PDB using the program Mogul, which cross references each deposited structure against similar data in the Cambridge Structural Database (CSD). Ligands associated with PDB structures are a common source of structural inaccuracy. In this study, a programmatic pipeline was developed to determine if ligand geometric accuracy could be improved using known computational tools. Ligands with dubious geometry were identified through a Python mining code. A sample set of the identified structures was remodeled into minimum energy conformations using the molecular dynamics program AMBER and then fit to the original experimental density maps using the molecular modeling program Coot. The refined models were compared to the original models in the PDB as well as to similar structures in the CSD using the deposition statistical validation server. Preliminary results suggest that the pipeline effectively identifies and improves ligand structures that possess inaccurate geometry. This method can be used to evaluate and improve the accuracy of specific ligands in structures both archived and pending deposition.Support or Funding InformationThis work was supported by an NSF REU and the RCSB PDB [NSF (DBI‐1338415), NIH, and DOE.]This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Neonicotinoids Activity Against Cowpea Aphids by Computational Estimation

In this study, the insecticidal activity against Cowpea aphids (Aphis craccivora) of a series of 23 phenylazo, pyrrole-, dihydropyrrole-fused and chain-opening nitromethyleneneonicotinoids was evaluated by using the multiple linear regression (MLR) and pharmacophore modelling. Conformer insecticide ensembles were modeled using the MMFF94s force field. Minimum energy conformers were employed to calculate structural parameters, which were related to the experimental pLC50 values. Several statistical criteria of goodness of fit and predictivity were checked to validate the models. Robust and predictable MLR models were obtained. Further, the Phase module from Schrodinger suite was engaged in the generation of the ligand-based pharmacophore models. The atom-based 3D-QSAR module from the aforementioned software was used for the validation of a best four-point pharmacophore model. The obtained significant statistical parameters attested thepharmacophore model validity. The MLR and pharmacophore models are useful for the prediction of new insecticides with activity against Cowpea aphids.

The structure of the anti-aging agent J147 used for treating Alzheimer's disease.

The molecular structure of the anti-aging agent J147 [systematic name: (E)-N-(2,4-dimethylphenyl)-2,2,2-trifluoro-N'-(3-methoxybenzylidene)acetohydrazide], C18H17F3N2O2, has been determined at 150 K. The crystal structure corresponds to the minimum-energy conformation in the gas phase calculated by density functional theory (DFT). 15 other conformations have been calculated and compared with the minimum, denoted 1111. NMR spectroscopic data have been obtained and compared with those from Gauge Independent Atomic Orbital (GIAO) calculations. DFT calculations allow the reduction of the 16 possible rotamers to the four most stable (i.e. 1111, 1112, 1121 and 1222); in addition, the calculated barriers connecting these minima are low enough to permit their interconversion. Comparison of the NMR spectroscopic results, both experimental and calculated, point to the 1121 isomer being present in chloroform solution.

Thermodynamic properties of ε-caprolactam and ε-caprothiolactam

This paper is concerned with experimental and computational thermochemical studies of ε-caprolactam and ε-caprothiolactam, molecules whose flexible ring structure provides several conformational forms.The gas-phase standard enthalpy of formation at the reference temperature of 298.15 K of the two title compounds have been determined from the enthalpy of formation in the crystalline phase, derived from bomb combustion calorimetry, and from the enthalpy of sublimation, derived from Calvet microcalorimetry and Knudsen effusion techniques.The equilibrium geometries and the thermodynamic properties of three minimum energy conformers obtained with the composite G3(MP2)//B3LYP approach were used to determine the conformational composition of the two lactam derivatives, by means of Boltzmann’s distribution. The computed gas-phase standard molar enthalpies of formation of ε-caprolactam and ε-caprothiolactam have been determined using hypothetical gas-phase reactions, taking into account the conformational compositions of each one of the species. This parameter together with the corresponding experimental one are compared.

Protein docking using constrained self-adaptive differential evolution algorithm

The objective of protein docking is to achieve a relative orientation and an optimized conformation between two proteins that results in a stable structure with the minimized potential energy. Constrained self-adaptive differential evolution (Cons_SaDE) algorithm is used to find the minimum energy conformation using proposed constraints such as boundary surface complementary interactions, non-bonded inter-atomic allowed distances and finding of interaction and non-interaction sites. With these constraints, Cons_SaDE is efficient enough to explore the promising solutions by gradually self-adapting the strategies and parameters learned from their previous experiences. Modified sampling scheme called rotate only representation is used to represent a docking conformation. GROMOS53A6 force field is used to find the potential energy. To test the performance of this algorithm, few bound and unbound complexes from Protein Data Bank (PDB) and few easy, medium and difficult complexes from Zlab Benchmark 4.0 are used. Buried surface area, root-mean-square deviation (RMSD) and correlation coefficient are some of the metrics applied to evaluate the best docked conformations. RMSD values of the best docked conformations obtained from five popular docking Web servers are compared with Cons_SaDE results, and nonparametric statistical tests for multiple comparisons with control method are implemented to show the performance of this algorithm. Cons_SaDE has produced good-quality solutions for the most of the data sets considered.

Computational screening of structure directing agents for the synthesis of zeolites. A simplified model

Abstract Zeolite micropores become more energetically stable by the occlusion of organic structure directing agents (templates). This energetic stabilisation, if approximated by van der Waals zeo-template interactions, can be calculated in a fast way by using modern computing techniques incorporating big data handling algorithms for massive screening. A software suite is presented which calculates an arbitrarily large 2-D matrix (template×zeolite) giving the zeo-template van der Waals interaction energy corresponding to the minimum energy conformation assuming one template molecule in a pure silica zeolite unit cell. With the goal of simplicity, the software only needs two coordinate input files of template and zeolite unit cell. Though a number of approximations have been considered, the software allows to compare, for a given template, which competing zeolite phases may become more stabilised. Applied to zeolite hypothetical databases, it may be of help to suggest templates for their synthesis.

A prelude to building mathematical models for polypeptide folding: analysis on the conformational potential energy hypersurface cross-sections of N-acetyl-glycyl-glycine-N′-methylamide

Finding a relationship on how a three-dimensional protein folds from its linear amino acid chain gets more complex with increasing chain length, so working on a smaller peptide conformational problem can provide initial ideas on what are the main molecular forces and how these influence the folding process. Following the study of conformations of amino acid units entering the proteins to understand the secondary structure of small peptides, this paper proposes mathematical models for the several two-rotor cross-sections of the five-dimensional N-acetyl-glycyl-glycine-N′-methylamide potential energy hypersurface (PEHS). These cross-sections are extracted along the first glycine subunit, with its coordinates fixed at the five energy minima of the glycine diamide. The resulting mathematical models yield an average RMSE of 1.36 kJ mol−1 and an average R2 of 0.9923 with respect to energy values obtained from DFT calculations. The minima geometries obtained from these models are also in good agreement with DFT-optimized energy minima conformers. An important aspect of this study also tackles the relationship between the PEHS of the glycyl-glycine diamide and its glycine subunits. It has been observed that there are deviations up to 28.35 kJ mol−1 and 29.52 kJ mol−1 between the PEHS cross-sections along γL and γD conformations, respectively, in the first glycine subunit. This may suggest that there are significant backbone–backbone intermolecular forces acting on the dipeptide. The abovementioned findings can help in developing more complex mathematical models for polypeptide folding from amino acid subunits.

Quantitative structure‐property relationship modeling of phosphoric polyester char formation

SummaryA required characteristic for almost all commercial polymers is to be flame retardant. This can be achieved if they have intrinsic flame‐retardant behavior, or by incorporating in them flame‐retardant materials. Polyphopshpoesters can be used as flame‐retardant materials for other polymers. In the present work, the multiple linear regression (MLR) technique was used for a quantitative structure‐property relationship study of char yields of 32 polyphosphonates and polyphosphates. The polyphosphoesters were modeled by their mer units, which were pre‐optimized using the MMFF94 force field. The molecular descriptors derived from the optimized structures were calculated for the minimum energy conformers, using the InstantJChem and Dragon programs. The polymer char yield was related to the structural descriptors, using MLR calculations, which were combined with a genetic algorithm for variable selection. Several stable MLR models were obtained, which were externally validated using seven compounds, as a test set. Model equations emphasize the important influence of structural descriptors to the polymer charring behavior. The best‐developed regression models contain Randić molecular profiles, Geometry, Topology and Atom‐Weights Assembly, and 3D Molecule Representation of Structures based on Electron diffraction descriptors, which influence positively the char formation. These models were used for the prediction of potential char formation of nine polyphosphonates and polyphosphates.

Validating strategy of quantitative ROESY analysis for structure determination of cyclodextrin inclusion complexes

Highly atom accurate structures of the inclusion complexes between benzydamine hydrochloride (BZY) and β-Cyclodextrin (β-CD) were determined by a method using quantitative ROESY analysis of computational models. Intermolecular contacts were examined in the ROESY spectrum that provided details of the portions of BZY encapsulated in the cavity and the probable mode of entry. Molecular docking studies presented negative binding energies which proved spontaneous complexation between β-CD and BZY and displayed two different modes of binding. Molecular mechanics (MM) studies were performed for both rings, in different orientations and from both cavity ends, to gauge their inclusion depth and mode of entry. Molecular dynamics (MD) studies were carried out to visualise the complexation process. Large number of minimum energy conformations from the MD runs were analysed by comparing their calculated intensities with experimental ROESY cross peak intensities to get the most probable structures of the ensembles.