Nuclear reactivity indices within regional density functional theory

Regional chemical potential values- _R have been obtained with the use of nuclear reactivity indices. Perturbational formulae use values of reactivity indices of isolated molecular fragments. The changes of the parameters (N_R,{ Q_i }_{i R}) within each fragment determine the value of the regional chemical potential after a chemical reaction. The computational scheme has been tested numerically along the chemical reaction path. We have studied a set of chemical reactions to obtain regional chemical potentials ( ) and regional transfer potentials ( ) for transition states of the following chemical reactions: HF+CO=HFCO, HCl+CO=HClCO, HF+SiO=HFSiO and HF+GeO=HFGeO. The results are reasonable and encouraging. Values of these indices show the possible reactivity directions of the transition states examined.     

Theoretical investigation of tautomerism in N-hydroxy amidines

A DFT study with QST3 approach method is used to calculate kinetic, thermodynamic, spectral and structural data of tautomers and transition state structures of some N-hydroxy amidines. All tautomers and transition states are optimized at the B3LYP/6-311++g** and B3LYP/aug-cc-pvtz level, with good agreement in energetic result with energies obtained from CBS-QB3, a complete basis set composite energy method. The result shows that the tautomer a (amide oxime) is more stable than the tautomer b (imino hydroxylamine) as is reported in the literature. In addition, our finding shows that, the energy difference between two tautomers is only in about 4–10 kcal/mol but the barrier energy found in traversing each tautomer to another one is in the range of 33–71 kcal/mol. Therefore, it is impossible to convert these two tautomers to each other at room temperature. Additionally, transition state theory is applied to estimate the barrier energy and reaction rate constants of the hydrogen exchange between tautomers in presence of 1–3 molecules of water. The computed activation barrier shows us that the barrier energy of solvent assisted tautomerism is about 9–20 kcal/mol and lower than simple tautomerism and this water-assisted tautomerism is much faster than simple tautomerism, especially with the assisting two molecules of water.     

A flexible approach for understanding protein stability

A distance constraint model (DCM) is presented that identifies flexible regions within protein structure consistent with specified thermodynamic condition. The DCM is based on a rigorous free energy decomposition scheme representing structure as fluctuating constraint topologies. Entropy non-additivity is problematic for naive decompositions, limiting the success of heat capacity predictions. The DCM resolves non-additivity by summing over independent entropic components determined by an efficient network-rigidity algorithm. A minimal 3-parameter DCM is demonstrated to accurately reproduce experimental heat capacity curves. Free energy landscapes and quantitative stability-flexibility relationships are obtained in terms of global flexibility. Several connections to experiment are made.     

Investigation of the Effect of Some Optically Active Imine Compounds on the Enzyme Activities of hCA‐I and hCA‐II under In Vitro Conditions: An Experimental and Theoretical Study

Inhibitors of carbonic anhydrase (hCA; EC 4.2.1.1) are used as medicines for many diseases. Therefore, they are very important. In this study, a known series of Schiff bases were synthesized and their effects on the activities of hCA‐I and hCA‐II, which are cytosolic isoenzymes of carbonic anhydrase, were investigated under in vitro conditions. The synthesized compounds (H1, H2, H3, and H4) were found to cause inhibition on enzyme activities of hCA‐1 and hCA‐II. IC₅₀ values of H1, H2, H3, and H4 compounds were 140, 88, 201, and 271 μM for hCA‐I enzyme activity and 134, 251, 79, and 604 μM for hCA‐II enzyme activity, respectively. The synthesized Schiff bases were characterized by several methods, including ¹H NMR, FT‐IR, elemental analysis, and polarimetric measurements. Correlation coefficient square values (R²) of comparison of the theoretical and experimental ¹H NMR shifts for H1, H2, H3, and H4 compounds were found as 0.9781, 0.9814, 0.9758, and 0.8635, respectively.     

Ratiometric fluorescent scaffold giving discrete response towards iodide ion: a combined experimental and DFT study

A novel ratiometric fluorescent receptor (Z)‐2‐(4‐[diethylamino]‐2‐hydroxybenzylideneamino) pyridine‐3‐carbaldehyde (3) bearing one phenolic OH and one aldehyde group as recognition sites was synthesized and characterized. The anion recognition behaviour of receptor 3 was evaluated by various spectroscopic (UV‐visible, fluorescence and ¹H nuclear magnetic resonance) methods and was validated by computational studies. The receptor showed fast response time, excellent selectivity and reproducibility towards iodide ion detection among the other surveyed anions, with a binding constant of 6.12 × 10⁴ M^?1 and a detection limit of 0.24 μM, thus confirming its potential applicability as a fluorescent sensor for iodide Copyright © 2014 John Wiley & Sons, Ltd.     

The reaction force and the transition region of a reaction

The reaction force F(R) and the position-dependent reaction force constant κF(R) are defined by F(R)=-∂V(R)/∂R and κ(R)=∂²V(R)/∂R², where V(R) is the potential energy of a reacting system along a coordinate R. The minima and maxima of F(R) provide a natural division of the process into several regions. Those in which F(R) is increasing are where the most dramatic changes in electronic properties take place, and where the system goes from activated reactants (at the force minimum) to activated products (at the force maximum). κ(R) is negative throughout such a region. We summarize evidence supporting the idea that a reaction should be viewed as going through a transition region rather than through a single point transition state. A similar conclusion has come out of transition state spectroscopy. We describe this region as a chemically-active, or electronically-intensive, stage of the reaction, while the ones that precede and follow it are structurally-intensive. Finally, we briefly address the time dependence of the reaction force and the reaction force constant.     

Malvin Z-chalcone: An unexpected new open cavity for the ferric cation

It is demonstrated that complexation between the ferric cation and the Z-chalcone of the naturally occurring anthocyanin malvin takes place in acidic aqueous solutions. The flexible open cavity of the Z-chalcone best fits the steric and electronic requirements of the ferric ion in water.     

Specific recognition of a tetrahedral phosphonamidate transition state analogue group by a recombinant antibody Fab fragment

Summary In order to obtain antibodies able to catalyse a peptide synthesis, a naive combinatorial library of human Fab antibody fragments was screened with the phosphonamidate transition state analogue of the reaction. Several Fab fragments were able to bind the analogue. Competitive binding studies performed with molecules containing representative parts of the hapten showed that two Fabs were able to recognize specifically the tetrahedral phosphorus present in the hapten.     

An investigation of the pyranose ring interconversion path of alpha-L-idose calculated using density functional theory

The interconversion pathways of the pyranose ring conformation of alpha-L-idose from a (4)C1 chair to other conformations were investigated using density functional calculations. From these calculations, four different ring interconversion paths and their transition state structures from the (4)C1 chair to other conformations, such as B(3,O), and (1)S3, were obtained. These four transition-state conformations cover four possible combinations of the network patterns of the hydroxyl group hydrogen bonds (clockwise and counterclockwise) and the conformations of the primary alcohol group (tg and gg). The optimized conformations, transition states, and their intrinsic reaction coordinates (IRC) were all calculated at the B3LYP/6-31G** level. The energy differences among the structures obtained were evaluated at the B3LYP/6-311++G** level. The optimized conformations indicate that the conformers of (4)C1, (2)S(O), and B(3,O) have similar energies, while (1)S3 has a higher energy than the others. The comparison of the four transition states and their ring interconversion paths, which were confirmed using the IRC calculation, suggests that the most plausible ring interconversion of the alpha-L-idopyranose ring occurs between (4)C1 and B(3,O) through the E3 envelope, which involves a 5.21 kcal/mol energy barrier.     

An Asymptotic Comparative Analysis of the Thermodynamics of Non-Covalent Association

There is an ambiguity in the theoretical models for computing association constants, the key observable in a laboratory, of non-covalent associations. We show that three different models give unique result asymptotically in the limit of strong associate. For weak associations, the disagreement reflects the nature of ill-defined ``associated complex' which can be defined, among various ways, either geometrically or thermodynamically depending on measurement techniques. Furthermore, even when the free energy of association is unique, the corresponding entropy and enthalpy can still be different from different types of measurements – a surprising source of entropy-enthalpy compensation. This work provides a mathematical basis for modeling non-covalent association processes in biology.     

A Semiempirical Transition State Structure for the First Step in the Alkaline Hydrolysis of Cocaine. Comparison between the Transition State Structure,the Phosphonate Monoester Transition State Analog,and a Newly Designed Thiophosphonate Transition State Analog

Semiempirical molecular orbital calculations have been performed for the first step in the alkaline hydrolysis of the neutral benzoylester of cocaine. Successes, failures, and limitations of these calculations are reviewed. A PM3 calculated transition state structure is compared with the PM3 calculated structure for the hapten used to induce catalytic antibodies for the hydrolysis of cocaine. Implications of these calculations for the computer–aided design of transition state analogs for the induction of catalytic antibodies are discussed.Supplementary material to this paper is available in electronic form at http://dx.doi.org/10.1007/s0089460020062     

LXA-1: a new plasmid-mediated β-lactamase giving low-level resistance

Abstract LXA-1, a novel plasmid-mediated β-lactamase, was observed in clinical isolates of Klebsiella oxytoca, Klebsiella pneumoniae, Citrobacter freundii and Enterobacter cloacae . All the strains additionally produced TEM-1 β-lactamase. LXA-1 had an M _r of 24 000 and a pI of 6.7. It hydrolysed benzyl-penicillin, ampicillin, carbenicillin and first generation cephalosporins, but not methicillin, oxacillin or cefotaxime. Clavulanate and cloxacillin were inhibitors. Studies of one of the E. cloacae isolates showed that LXA-1 was encoded by a 41-MDa IncFII plasmid distinct from that encoding TEM-1 enzyme in the strain. Transconjugants which acquired LXA-1 production, but not TEM-1, exhibited only low-level resistance to substrate β-lactams.     

An unsaturated peptidomimetic assembly derived from a carbohydrate.

A strategy has been established for the synthesis of peptidomimetics derived from unsaturated carbohydrates, and exemplified by the use of methyl 2,6-anhydro-7-azido-3,7-deoxy-4,5-O-isopropylidene-D-lyxo-hept-2-enonate 9 as a dipeptide 'monomer' which can be elaborated from either end. Selective reduction of 9 gives a protected pseudodipeptide ester suitable for use as an amino component, and saponification gives an azido acid suitable for use as a carboxyl component. The 'dimer' product of coupling these two components with TBTU can be similarly elaborated at either end to give a 'trimer' and a further cycle of selective reduction and coupling gave a 'tetramer', 17, a pseudo-octapeptide.     

Transition state analysis of the complex between coagulation factor VIIa and tissue factor: suggesting a sequential domain-binding pathway

Injury of a blood vessel exposes membrane-bound tissue factor (TF) to blood, which allows binding of coagulation factor VIIa (FVIIa). This initiation of the coagulation cascade is dictated by a specific multi-domain interaction between FVIIa and TF. To examine the energies involved in the transition state of the FVIIa:TF complex, various residues in the extracellular part of TF (sTF) that are known to interact with FVIIa were replaced with a smaller cysteine residue. Determination of Phi values in each of the positions using surface plasmon resonance measurements enabled us to characterize the transition state complex between the resulting sTF variants and FVIIa. We found that the interactions in the transition state seemed to be most pronounced between the protease domain of FVIIa and sTF while detailed specific interactions between the Gla-domain and sTF were missing. Thus, the transition state energy data indicate a sequential binding event between these two macromolecules.     

Spectroscopic characterization of a semi-stable, charge-separated state in Cu-substituted reaction centers from Rhodobacter sphaeroides

In reaction centers from Rhodobacter sphaeroides exposed to continuous illumination in the presence of an inhibitor of the Q_A⁻ to Q_B electron transfer, a semi-stable, charge-separated state was formed with halftimes of formation and decay of several minutes. When the non-heme iron was replaced by Cu²⁺, the decay of the semi-stable, charge-separated state became much slower than in centers with bound Fe²⁺ with about the same rate constant for formation. In Cu²⁺-substituted reaction centers, the semi-stable state was associated with an EPR signal, significantly different from that observed after chemical reduction of the acceptor-side quinone or after illumination at low temperature, but similar to that of an isolated Cu²⁺ in the absence of magnetic interaction. The EPR results, obtained with Cu²⁺-substituted reaction centers, suggest that the slow kinetics of formation and decay of the charge-separated, semi-stable state is associated with a structural rearrangement of the acceptor side and the immediate environment of the metal-binding site.     

一类具有时滞的微生物连续培养数学模型研究

研究了具有强核函数时滞的微生物连续培养数学模型,利用泛函微分方程理论和数值解法得到系统在一定操作条件下存在Hopf分叉以及分叉值随操作参数变化的规律,并研究了Hopf分叉产生的方向及周期解的稳定性,绘制了周期解的图形和相图.该模型定性地描述了实验中的振荡和过渡现象.最后与弱核函数时滞模型、离散时滞模型进行比较,分析了它们对多态、振荡等动态行为的影响。     

Computational investigation of ethene trimerisation catalysed by cyclopentadienyl chromium complexes

Intermediates and transition states of the reaction cycle for the trimerisation of ethene catalysed by the initial catalyst precursor [η⁵-CpCrCl₂]₂ have been characterised by modeling, starting from the species η⁵-CpCrMe₂. This is a simplified model system of the actual catalytically active system containing bulky cyclopentadienyls. The ground-state multiplicity configuration was determined to be that of a quartet, in the case of non-chlorinated Cr(III) species, and a triplet for corresponding chlorinated Cr(IV) analogues. Geometry optimizations were performed on all intermediates, using their ground-state multiplicity, and all relevant transition states were located and subsequently optimised. The effect of an additional chlorine ligand on the chromium centre (viz. species of the form η⁵-CpCrClL_n) on the activation energy barriers was also determined for two key high energy transformations. It was found that the activation energy barriers are lowered significantly upon the addition of a chlorine ligand to the chromium centre. The rate determining step for the non-chlorinated, Cr(III) system, was calculated as requiring a free energy value of 88 kJ mol⁻¹, with the chlorinated Cr(IV) analogue at 56 kJ mol⁻¹ in the same step. The process of ethene tetramerisation was found to be unfeasible with the system, with a free energy barrier of 162 kJ mol⁻¹ associated with this transformation.     

Substitution effect on new Co(II) addition compounds with salicylaldehydes and the nitrogenous bases phen or neoc: Crystal and molecular structures of [Co(5-NO2-salicylaldehyde)2(phen)], [Co(5-CH3-salicylaldehyde)2(neoc)] and [Co(5-Cl-salicylaldehyde)2(neoc)]

The cobalt(II) addition compounds [Co(X-salo)₂(Y)], where X-salo is the anion of substituted salicylaldehydes (X = 3-OCH₃, 5-CH₃, 5-Cl, 5-NO₂ and Y = the neutral 1,10 phenanthroline or neocuproine), were synthesized and characterized by physicochemical and spectral (IR, UV-Vis) data. Theoretical calculations (DFT, ZINDO, TD DFT) with gaussian 03 for the prediction of the electronic spectrum for the compounds, gave good correlation with the experimental one in the solid state and in solution. The cyclic voltammetry study in CH₃CN gave all the expected waves for the redox processes of the metal Co(II) and the ligands phen or neoc and salicylaldehydes. The X-ray diffraction study of three compounds [Co(5-NO₂-salo)₂(phen)], [Co(5-CH₃-salo)₂(neoc)] and [Co(5-Cl-salo)₂(neoc)] verified their analogous proposed octahedral arrangement of the ligands around the cobalt(II) atom.