DFT calculations on nitrodiborane compounds as new potential high energy materials

We have used DFT methods to determine the structures and thermochemistry of several nitro-substituted diborane molecules in an attempt to rate their potential as high energy materials. The properties of nitrodiborane, three isomers of dinitrodiborane, trinitrodiborane, and tetranitrodiborane were calculated using the B3LYP density functional method. Our results indicate that the absolute enthalpy of combustion decreases with increasing nitro content, in contrast with other nitro-substituted systems that have been studied previously.     

Direct NMR observation and DFT calculations of a hydrogen bond at the active site of a 44 kDa enzyme

A hydrogen bond between the amide backbone of Arg7 and the remote imidazole side chain of His106 has been directly observed by improved TROSY-NMR techniques in the 44 kDa trimeric enzyme chorismate mutase from Bacillus subtilis. The presence of this hydrogen bond in the free enzyme and its complexes with a transition state analog and the reaction product was demonstrated by measurement of ¹⁵N-¹⁵N and ¹H-¹⁵N trans-hydrogen bond scalar couplings, ^2h J _NN and ^1h J _HN, and by transfer of nuclear polarization across the hydrogen bond. The conformational dependences of these coupling constants were analyzed using sum-over-states density functional perturbation theory (SOS-DFPT). The observed hydrogen bond might stabilize the scaffold at the active site of BsCM. Because the Arg7-His106 hydrogen bond has not been observed in any of the high resolution crystal structures of BsCM, the measured coupling constants provide unique information about the enzyme and its complexes that should prove useful for structural refinement of atomic models.     

DFT study of new bipyrazole derivatives and their potential activity as corrosion inhibitors

In the present work, a theoretical study of five bipyrazolic-type organic compounds, 4-{bis[(3,5-dimethyl-1H-pyrazolyl-1-yl)methyl]-amino}phenol (1), N1,N1-bis[(3,5-dimethyl-1H-pyrazol-1-yl)methyl}]-N4,N4-dimethyl-1,4-benzenediamine (2), N,N-bis[(3,5-dimethyl-1H-pyrazol-1-yl)methyl]aniline (3), 4-[bis(3,5-dimethyl pyrazol-1-yl-methyl)-amino]butan-1-ol (4) and ethyl4-[bis(3,5-dimethyl-1H-pyrazol-1-yl-methyl) aminobenzoate] (5), has been performed using density functional theory (DFT) at the B3LYP/6-31G(d) level in order to elucidate the different inhibition efficiencies and reactive sites of these compounds as corrosion inhibitors. The efficiencies of corrosion inhibitors and the global chemical reactivity relate to some parameters, such as EHOMO, ELUMO, gap energy (ΔE) and other parameters, including electronegativity (χ), global hardness (η) and the fraction of electrons transferred from the inhibitor molecule to the metallic atom (ΔN). The calculated results are in agreement with the experimental data on the whole. In addition, the local reactivity has been analyzed through the Fukui function and condensed softness indices.     

Low-energy conformers of pamidronate and their intramolecular hydrogen bonds: a DFT and QTAIM study

Extensive DFT and ab initio calculations were performed to characterize the conformational space of pamidronate, a typical pharmaceutical for bone diseases. Mono-, di- and tri-protic states of molecule, relevant for physiological pH range, were investigated for both canonical and zwitterionic tautomers. Semiempirical PM6 method were used for prescreening of the single bond rotamers followed by geometry optimizations at the B3LYP/6-31++G(d,p) and B3LYP/6-311++G(d,p) levels. For numerous identified low energy conformers the final electronic energies were determined at the MP2/6-311++G(2df,2p) level and corrected for thermal effects at B3LYP level. Solvation effects were also considered via the COSMO and C-PCM implicit models. Reasonable agreement was found between bond lengths and angle values in comparison with X-ray crystal structures. Relative equilibrium populations of different conformers were determined from molecular partition functions and the role of electronic, vibrational and rotational degrees of freedom on the stability of conformers were analyzed. For no level of theory is a zwitterionic structure stable in the gas-phase while solvation makes them available depending on the protonation state. Geometrically identified intramolecular hydrogen bonds were analyzed by QTAIM approach. All conformers exhibit strong inter-phosphonate hydrogen bonds and in most of them the alkyl-amine side chain is folded on the P-C-P backbone for further hydrogen bond formation.

Theoretical study on small clusters of BaTiO3 using DFT calculations

Using density functional theory with the generalised gradient approximation, the structural and electronic properties of small (BaTiO₃)_n (n = 1–4) clusters have been studied. All the analysed growth modes were observed to consist of the same unit block, which in turn is similar to the well-known (TiO₂)₂ cluster. The BaTiO₃ and (BaTiO₃)₂ systems were observed to adopt analogous geometries to the ground state of (TiO₂)_n clusters with C_s and D_2h symmetries, respectively. The calculated value of the energy gap for the studied (BaTiO₃)_n clusters tends to approach that observed for its tetragonal bulk BaTiO₃ counterpart when n ≥ 3 is considered; the same tendency is observed for the Ba–Ba, Ba–Ti, Ti–O and Ba–Ti interatomic distances. For all the (BaTiO₃)_n clusters, the structural characteristics of their respective isomers were explored.     

Tocopheramines and tocotrienamines as antioxidants: ESR spectroscopy,rapid kinetics and DFT calculations

Tocopheramines (TNH₂) and tocotrienamines (T₃NH₂) are analogues of tocopherols (TOH) and tocotrienols in which phenolic OH is replaced by NH₂. It was shown in previous studies that TNH₂ and T₃NH₂ act as potent antioxidants. In this study we compared the one-electron oxidation of TNH₂/T₃NH₂ by diphenyl picryl hydrazyl (DPPH) and galvinoxyl (GOX) radicals with the one of α-TOH as a reference compound using ESR spectroscopy, stopped flow spectrophotometry and density functional theory (DFT) calculations. ESR spectroscopy revealed the presence of tocopheramine radicals during electrochemical oxidation of α-TNH₂. Kinetic measurements demonstrated that in apolar n-hexane TNH₂/T₃NH₂ derivatives reacted two to three orders of magnitude slower than α-TOH with the model radicals. DFT calculations indicated that this correlates well with the higher bond dissociation energy (BDE) for N–H in TNH₂ than for O–H in α-TOH in pure H-atom transfer (HAT). In the more polar medium ethanol TNH₂/T₃NH₂ derivatives partially reacted faster than α-TOH depending on the reaction partner. DFT calculations suggest that this is due to reaction mechanisms alternative to HAT. According to thermochemistry data sequential proton loss and electron transfer (SPLET) is more favored for α-TOH in ethanol than for TNH₂. Therefore, for TNH₂ a contribution of the alternative mechanism of sequential electron transfer–proton transfer (SET–PT) could be a possible explanation. These data show that the antioxidant reactivity strongly depends on the structure, reaction partners and environment. According to these findings TNH₂/T₃NH₂ should be superior as antioxidants over α-TOH in polar head group regions of membranes but not in the apolar core of lipid bilayers.     

Myosin-V as a mechanical sensor: an elastic network study

According to recent experiments, the molecular-motor myosin behaves like a strain sensor, exhibiting different functional responses when loads in opposite directions are applied to its tail. Within an elastic-network model, we explore the sensitivity of the protein to the forces acting on the tail and find, in agreement with experiments, that such forces invoke conformational changes that should affect filament binding and ADP release. Furthermore, conformational responses of myosin to the application of forces to individual residues in its principal functional regions are systematically investigated and a detailed sensitivity map of myosin-V is thus obtained. The results suggest that the strain-sensor behavior is involved in the intrinsic operation of this molecular motor.     

A hybrid-type approach with MD and DFT calculations for evaluation of redox potential of molecules

A simple calculation method to evaluate the redox potential of molecules by using a hybrid-type calculation with molecular dynamics (MD) and density functional theory calculations is presented with discussions of the difference of the redox potential. In our hybrid method, the standard Gibbs free energy of the molecules, acetone and 3-pentanone, in the redox reaction, is estimated from the average of ionisation free energy and the excess chemical potentials of the reduced and oxidised molecules according to the Born–Haber cycle by sampled configurations from the MD simulation. The difference of the redox potentials between the two molecules is in agreement with the experimental data within the standard deviation.     

Possible role of hydrogen cyanide in chemical evolution. The oligomerization and condensation of hydrogen cyanide

The rate of cyanide oligomerization is independent of the presence of added nucleophiles such as azide, monomethylamine or triethylamine and is dependent only on the pH of the reaction mixture. The products formed, with the exception of urea, are also independent of the nucleophiles used to initiate reaction. In the presence of monomethylamine, monomethylurea is the main neutral product instead of urea, suggesting the intermediacy of cyanate. Evidence is presented which suggests that cyanogen may be the precurser to both cyanate and oxalic acid in the cyanide Oligomerization.     

Nitroborazines as potential high energy materials: density functional theoretical calculations

As part of a search for new high energy density materials, we used density functional theoretical calculations to determine the thermochemical properties of various nitro-substituted borazine molecules. Optimized geometries, vibrational frequencies and spectra, and enthalpies of formation and combustion were determined for nitroborazine, dinitroborazine, trinitroborazine, and methyltrinitroborazine with substituents on either the boron atoms or the nitrogen atoms of the parent borazine ring. Our results indicate that the specific enthalpy of combustion ranged from 4 to 11 kJ g⁻¹, with increasing substitution of nitro groups lowering the energy of combustion per unit mass.     

Radiation chemistry of overirradiated aqueous solutions of hydrogen cyanide and ammonium cyanide

Summary The radiolysis of aqueous solutions (O₂-free) of HCN and NH₄CN was examined at very large doses of⁶⁰Co gamma radiation (up to 230 Mrad). In this dose range the cyanide initially present (0.12 M) is decomposed and only its radiolytic products participate in the radiation-induced chemical process. It has been found that the weight of the dry residue containing the mixture of nonvolatile radiolytic products increases as doses increase up to 40 Mrad (up to about 4 g/l), but with further dose increases remains practically unchanged (NH₄CN) or decreases slightly (HCN). Carboxylic and amino acids are present in overirradiated samples. At increasing doses their concentrations decrease, with the exception of oxalic and malonic acids, which are continually produced and accumulate. This is also the case with the abundant NH₃ and CO₂, as well as with several other products that were generated at lower radiation-chemical yields. The molecular weights of the radiolytic products are up to 20,000 daltons throughout the dose range studied. Their amounts gradually change with increasing doses above 30 Mrad: The compounds with M_w between 2,000 and 6,000 daltons become more abundant, while the amounts of polymers with M_w between 6,000 and 20,000 decrease. The relevance of these findings for studies of chemical evolution is considered.     

2,6-diaminopyridine derivatives as models of molecular sensor for nucleic acid base detection: ab initio calculations of electronic effects induced by hydrogen bonds formation

The performance of a molecular sensor for detecting nucleic acid base was studied by molecular orbital calculations of model compounds. The model compounds consist of a detecting unit (pyridine derivative), a conducting unit (benzene) and a connection between them. The changes of the HOMO, LUMO energy levels and charge distributions of the conducting unit by the hydrogen bonds formation between the detecting unit and thymine were studied. The calculations show that the choice of the connection and its position are significantly important to efficiently transmit the electronic effects to the conducting unit. The comparison with aminopyridine, where the pyridine ring plays both detecting and conducting units, shows that the electronic effects are transmitted quite efficiently, if the connection is properly selected. The size of the electronic effects by the formation of the hydrogen bonds were also compared with those induced by the change of the torsional angle between the pyridine and benzene rings and by substitution of the benzene ring.     

Rapid sodium cyanide depletion in cell culture media: outgassing of hydrogen cyanide at physiological pH

During the course of in vitro studies on cyanide exposure with SH-SY5Y human neuroblastoma cells, we found that sodium cyanide (NaCN) up to a concentration of 10 mM had no significant toxic effect under our culture conditions. Further investigation of this apparent cyanide resistance revealed that the sodium cyanide was being rapidly depleted from the cell culture medium. Cyanide was interacting with constituents of the cell culture medium and was somehow being detoxified or removed from solution. The reaction of cyanide with cell culture media in 96-well culture plates reduced cyanide concentrations rapidly (80-90% in 2 h at 37 degrees C). Running the same reaction in capped tubes significantly reduced cyanide loss from solution. Incubation of cyanide with individual constituents of the cell culture medium in solution showed that glucose, phenol red, and amino acids all acted to detoxify or remove cyanide from solution. When amino acids or buffers were incubated with sodium cyanide in aqueous solution at pH 7.4, hydrogen cyanide (HCN) was found to degas from the solutions. We compared HCN outgassing over a range of pH values. As expected, HCN remained very soluble at high pH, but as the pH was reduced to 7.0, the rate of HCN formation and outgassing increased dramatically. Acid-base reactions involving cyanide and proton donors, such as amino acids and other cell culture media constituents, at physiological pH result in rapid HCN outgassing from solution at 37 degrees C. These results indicate that previous in vitro cyanide toxicity studies done in standard culture media with prolonged incubation times using gas-exchanging culture containers might have to be reevaluated in light of the fact that the effective cyanide concentrations in the culture media were significantly lower than reported.     

Pentacycloundecane lactam vs lactone norstatine type protease HIV inhibitors: binding energy calculations and DFT study

Background

Novel pentacycloundecane (PCU)-lactone-CO-EAIS peptide inhibitors were designed, synthesized, and evaluated against wild-type C-South African (C-SA) HIV-1 protease. Three compounds are reported herein, two of which displayed IC₅₀ values of less than 1.00 μM. A comparative MM-PB(GB)SA binding free energy of solvation values of PCU-lactam and lactone models and their enantiomers as well as the PCU-lactam-NH-EAIS and lactone-CO-EAIS peptide inhibitors and their corresponding diastereomers complexed with South African HIV protease (C-SA) was performed. This will enable us to rationalize the considerable difference between inhibitory concentration (IC₅₀) of PCU-lactam-NH-EAIS and PCU-lactone-CO-EAIS peptides.

Results

The PCU-lactam model exhibited more negative calculated binding free energies of solvation than the PCU-lactone model. The same trend was observed for the PCU-peptide inhibitors, which correspond to the experimental activities for the PCU-lactam-NH-EAIS peptide (IC₅₀ = 0.076 μM) and the PCU-lactone-CO-EAIS peptide inhibitors (IC₅₀ = 0.850 μM). Furthermore, a density functional theory (DFT) study on the natural atomic charges of the nitrogen and oxygen atoms of the three PCU-lactam, PCU-lactim and PCU-lactone models were performed using natural bond orbital (NBO) analysis. Electrostatic potential maps were also used to visualize the electron density around electron-rich regions. The asymmetry parameter (η) and quadrupole coupling constant (χ) values of the nitrogen and oxygen nuclei of the model compounds were calculated at the same level of theory. Electronic molecular properties including polarizability and electric dipole moments were also calculated and compared. The Gibbs theoretical free solvation energies of solvation (∆G_solv) were also considered.

Conclusions

A general trend is observed that the lactam species appears to have a larger negative charge distribution around the heteroatoms, larger quadrupole constant, dipole moment and better solvation energy, in comparison to the PCU-lactone model. It can be argued that these characteristics will ensure better eletronic interaction between the lactam and the receptor, corresponding to the observed HIV protease activities in terms of experimental IC₅₀ data.

Electronic supplementary material

The online version of this article (doi:10.1186/s12929-015-0115-5) contains supplementary material, which is available to authorized users.     

Metabolism of hydrogen cyanide by higher plants

A survey has been made of the occurrence and distribution of three enzymes which metabolize cyanide in a variety of higher plants including both cyanogenic and non-cyanogenic species. The enzymes investigated were β-cyanoalanine synthase, rhodanese and formamide hydrolyase. β-Cyanoalanine synthase was found to be present in every higher plant tested whereas rhodanese was found to occur far less commonly in plants. Formamide hydrolyase activity was not detected in any of the higher plants tested.