Molecular modeling and multi-spectroscopic approaches to study the interaction between antibacterial drug and human immunoglobulin G.

Mechanistic and conformational studies on the interaction of sulfamethoxazole (SMX) with human immunoglobulin G (HIgG) were performed by molecular modeling and multi-spectroscopic methods. The interaction mechanism was firstly predicted through molecular modeling that confirmed the interaction between SMX and HIgG. The binding parameters and thermodynamic parameters at different temperatures had been calculated according to the Stern-Volmer, Scatchard, Sips and Van 't Hoff equations, respectively. Experimental results showed that the fluorescence intensity of HIgG was quenched by the gradual addition of SMX. The binding constants of SMX with HIgG decreased with the increase of temperature, which meant that the quenching mechanism was a static quenching. Meanwhile, the results also confirmed that there was one independent class of binding site on HIgG for SMX during their interaction. The thermodynamic parameters of the reaction, namely standard enthalpy ΔH(0) and entropy ΔS(0), had been calculated to be -14.69 kJ·mol(-1) and 22.99 J·mol(-1) ·K(-1), respectively, which suggested that the electrostatic and hydrophobic interactions were the predominant intermolecular forces in stabilizing the SMX-HIgG complex. Furthermore, experimental results obtained from three-dimensional fluorescence spectroscopy, UV-vis absorption spectroscopy and circular dichroism (CD) spectroscopy confirmed that the conformational structure of HIgG was altered in the presence of SMX.

Can a single water molecule really affect the HO2 + NO2 hydrogen abstraction reaction under tropospheric conditions?

The effect of a single water molecule on the HO2 + NO2 hydrogen abstraction reaction has been investigated by employing B3LYP and CCSD(T) theoretical approaches with the aug-cc-pVTZ basis set. The reaction without water has three types of reaction channels on both singlet and triplet potential energy surfaces, depending on how the HO2 radical approaches NO2. These correspond to the formation of trans-HONO + O2, cis-HONO + O2 and HNO2 + O2. Our calculated results show that triplet reaction channels are favorable and their total rate constant, at 298 K, is 2.01 × 10(-15) cm(3) molecule(-1) s(-1), which is in good agreement with experimental values. A single water molecule affects each one of these triplet reaction channels in the three different reactions of H2O···HO2 + NO2, HO2···H2O + NO2 and NO2···H2O + HO2, depending on the way the water interacts. Interestingly, the water molecule in these reactions not only acts as a catalyst giving the same products as the naked reaction, but also as a reactant giving the product of HONO2 + H2O2. The total rate constant of the H2O···HO2 + NO2 reaction is estimated to be slower than the naked reaction by 6 orders of magnitude at 298 K. However, the total rate constants of the HO2···H2O + NO2 and NO2···H2O + HO2 reactions are faster than the naked reaction by 4 and 3 orders of magnitude at 298 K, respectively. Their total effective rate constant is predicted to be 1.2 times that of the corresponding total rate constant without water at 298 K, which is in agreement with the prediction reported by Li et al. (science, 2014, 344, 292-296).

Is the contribution of cis and trans protonated 5-methylcytosine-SO3(-) isomers equal in the conversion to thymine-SO3(-) under bisulfite conditions? A theoretical perspective.

Cytosine (Cyt) can be converted to 5-methylcytosine (5-MeCyt) in CpG sequences of DNA. Conventional bisulfite sequencing can discriminate Cyt from 5-MeCyt, however inappropriate conversion of 5-MeCyt to thymine and a failure to convert Cyt to uracil always occur when Cyt and 5-MeCyt are treated with bisulfite, which would lead to erroneous estimates of DNA methylation densities. Here, the direct hydrolytic deamination of cis (paths A-C) and trans (paths A'-C') 5-MeCytN3(+)-SO3(-) isomers with bisulfite have been explored at the MP2/6-311++G(3df,3pd)//B3LYP/6-311++G(d,p) level. The activation free energies (ΔG(s-a≠)) of the cis and trans 5-MeCytN3(+)-SO3(-) isomers' paths exhibit no obvious differences, implying both isomers may make an equal contribution to the hydrolytic deamination of 5-MeCyt under bisulfite conditions. It is greatly expected that these results could aid experimental scientists to explore new methods to avoid the formation of the deaminated reactants (5-MeCytN3(+)-SO3(-)). Meanwhile, the HSO3(-)-induced direct hydrolytic deamination of cis and trans 5-MeCytN3(+)-SO3(-) isomers is represented by paths A and A', respectively, and has been further explored in the presence of two water molecules. It was found that the contribution of two water molecules renders the HSO3(-)-induced direct hydrolytic deamination of cis and trans 5-MeCytN3(+)-SO3(-) isomers by paths A and A' favourable. In addition, the ΔG(s-a≠) values (85.74-85.34 kJ mol(-1)) of the rate-limiting steps of the two water-mediated paths A and A' are very close to that of the theoretical value for CytN3(+)-SO3(-) (88.18 kJ mol(-1)), implying that the free barrier gap between Cyt and 5-MeCyt is very small under bisulfite conditions. This further suggests that bisulfite sequencing technology may be easily influenced by the external environment.

N'-(4-Hydr-oxy-3-methoxy-benzyl-idene)-4-methoxy-benzohydrazide monohydrate.

In the title compound, C(16)H(16)N(2)O(4)·H(2)O, the dihedral angle between the two aromatic rings is 19.6 (2)°. In the crystal structure, mol-ecules are linked into a three-dimensional network by inter-molecular N-H⋯O, O-H⋯N and O-H⋯O hydrogen bonds.

N'-(5-Bromo-2-hydr-oxy-3-methoxy-benzyl-idene)-4-hydr-oxy-3-methoxy-benzohydrazide dihydrate.

In the title compound, C(16)H(15)BrN(2)O(5)·2H(2)O, the dihedral angle between the two aromatic rings is 2.9 (2)° and an intra-molecular O-H⋯N hydrogen bond is observed. One of the water mol-ecule is disordered over two positions, with occupancies of 0.83 (3) and 0.17 (3). In the crystal structure, mol-ecules are linked into a three-dimensional network by inter-molecular O-H⋯O, O-H⋯(O,O), O-H⋯N and N-H⋯O hydrogen bonds. π-π inter-actions involving Br-substituted benzene rings, with a centroid-centroid distance of 3.552 (3) Šare also observed.

N'-(3-Eth-oxy-2-hydroxy-benzyl-idene)-4-hydr-oxy-3-methoxy-benzohydrazide monohydrate.

In the title compound, C(17)H(18)N(2)O(5)·H(2)O, the dihedral angle between the two aromatic rings is 7.86 (7)° and an intra-molecular O-H⋯N hydrogen bond is observed. In the crystal structure, mol-ecules are linked into a three-dimensional network by inter-molecular O-H⋯O and N-H⋯O hydrogen bonds.

N'-(2-Hydroxy-benzyl-idene)-2-methoxy-benzohydrazide monohydrate.

In the title compound, C(15)H(14)N(2)O(3)·H(2)O, the Schiff base mol-ecule is approximately planar, with a dihedral angle between the two aromatic rings of 10.2 (3)°. The mol-ecular structure is stabilized by O-H⋯N and N-H⋯O hydrogen bonds. In the crystal structure, the Schiff base and water mol-ecules are linked together by inter-molecular O-H⋯O hydrogen bonds, forming chains parallel to the a axis.

4-Chloro-N'-(2-hydroxy-benzyl-idene)benzohydrazide monohydrate.

The asymmetric unit of the title compound, C(14)H(11)ClN(2)O(2)·H(2)O, contains a Schiff base mol-ecule and a water mol-ecule of crystallization. The dihedral angle between the two aromatic rings is 27.3 (4)°. In the crystal structure, mol-ecules are linked into a two-dimensional network parallel to the bc plane by inter-molecular O-H⋯O and N-H⋯O hydrogen bonds involving the water mol-ecules.

2-Meth-oxy-N'-(2-methoxy-benzyl-idene)benzohydrazide.

The title Schiff base compound, C(16)H(16)N(2)O(3), was derived from the condensation of 2-methoxy-benzaldehyde with 2-methoxy-benzohydrazide in an ethanol solution. The dihedral angle between the two aromatic rings is 87.5 (3)°. In the crystal structure, the mol-ecules are linked into chains running parallel to the a axis by inter-molecular N-H⋯O hydrogen bonds.

Effects of protonation and C5 methylation on the electrophilic addition reaction of cytosine: a computational study.

The mechanism for the effects of protonation and C5 methylation on the electrophilic addition reaction of Cyt has been explored by means of CBS-QB3 and CBS-QB3/PCM methods. In the gas phase, three paths, two protonated paths (N3 and O2 protonated paths B and C) as well as one neutral path (path A), were mainly discussed, and the calculated results indicate that the reaction of the HSO(3)(-) group with neutral Cyt is unlikely because of its high activation free energy, whereas O2-protonated path (path C) is the most likely to occur. In the aqueous phase, path B is the most feasible mechanism to account for the fact that the activation free energy of path B decreases compared with the corresponding path in the gas phase, whereas those of paths A and C increase. The main striking results are that the HSO(3)(-) group directly interacts with the C5═C6 bond rather than the N3═C4 bond and that the C5 methylation, compared with Cyt, by decreasing values of global electrophilicity index manifests that C5 methylation forms are less electrophilic power as well as by decreasing values of NPA charges on C5 site of the intermediates make the trend of addition reaction weaken, which is in agreement with the experimental observation that the rate of 5-MeCyt reaction is approximately 2 orders of magnitude slower than that of Cyt in the presence of bisulfite. Apart from cis and trans isomers, the rare third isomer where both the CH(3) and SO(3) occupy axial positions has been first found in the reactions of neutral and protonated 5-MeCyt with the HSO(3)(-) group. Furthermore, the transformation of the third isomer from the cis isomer can occur easily.

An unusual fan-type polyanion with a silver cation located at the axial center, [AgAsIII2(AsIIIAsVMo4O18(OH)2)3]11-.

A new type of polyoxomolybdate containing mixed-valence arsenic, [AgAs(III)(2)(As(III)As(V)Mo(4)O(18)(OH)(2))(3)](11-) (1), has been synthesized. Single-crystal X-ray analysis was carried out on (NH(4))(5)(C(2)H(9)N(2))(4.5)H(1.5)[AgAs(III)(2)(As(III)As(V)Mo(4)O(18)(OH)(2))(3)]·14H(2)O (1a) and (NH(4))(11)[AgAs(III)(2)(As(III)As(V)Mo(4)O(18)(OH)(2))(3)]·16H(2)O (1b). The polyanion is composed of three unprecedented [As(III)As(V)Mo(4)O(18)(OH)(2)](6-) subunits linked together by two AsO(3) trigonal-pyramidal structures from both sides via sharing six bridging oxygen atoms, and a silver cation is enclosed in the center of the polyanion and coordinated by three As atoms with the As-Ag-As bond angle of 120°, to lead to a fan-like structure with an approximative C(3h) symmetry. The polyanion was also characterized by IR, X-ray photoelectron spectroscopy and thermogravimetry-differential scanning calorimetry. The stability of [AgAs(III)(2)(As(III)As(V)Mo(4)O(18)(OH)(2))(3)](11-) in an aqueous solution was investigated by electronic absorbance spectroscopy and electrospray ionization mass spectrometry, and the possible disaggregation mechanism of the polyanion is proposed.