Electrostatic Potential Contour Research Articles

Vibrational Spectroscopic and Structural Investigations of 2-Amino-6-Methoxy-3-Nitropyridine: a DFT Approach

The conformational analysis of 2-amino-6-methoxy-3-nitropyridine molecule (AMNP) has been carried out using density functional theory calculations. The vibrational spectra of the molecule is simulated theoretically and compared experimentally, and the vibrational frequencies are assigned on the basis of potential energy distribution calculations. Electronic properties of the molecule derived from the theoretical ultraviolet–visible spectrum are validated experimentally. The higher non-linear optical activity of the molecule is indicated in the first-order hyperpolarizability calculations. The natural bond orbital and Mulliken atomic charge distribution analysis confirm intramolecular charge transfers and intramolecular interactions. The Frontier molecular orbitals are plotted, and the related molecular properties are calculated and discussed. The molecular electrostatic potential contour map is simulated. As the presence of intramolecular interactions and the associated charge transfers between the pyridine ring of AMNP molecule and the lone pair of oxygen is a common molecular feature of a pharmaceutical compound, this investigation paves the way for its possible biomedical applications. Further, the considerably higher non-linear optical (NLO) activity of the molecule identified suggests its potential applications in the design of new optical materials.

Potentiometric, Raman spectroscopy and DFT study of pentaaqua glycine aluminum(III) complex in aqueous solution

Aluminum ion bioaccumulation is associated with the formation of β-amyloid peptide, a main microscopic characteristic of Alzheimer’s disease. β-amyloid affects glucose transport and consequently limits glycine synthesis. Glycine is an important amino acid in several body functions and it acts as an inhibitory neurotransmitter in the central nervous system. Moreover, aluminum glycinate salt is used as medication. The complex formed by aluminum(III) and glycine in aqueous solution at metal-to-ligand ratio of 1:1 has been studied by potentiometry, Raman spectroscopy and quantum chemical calculations (DFT:B3LYP/6-311++G**). Atomic charges, electrostatic potential contour surface, electrostatic potential map and donor–acceptor second order perturbative energies were examined. Potentiometry data revealed complexion formation. Distributions of species pointed out the better value to perform the Raman analyses. Raman data was used to confirm complexion formation and indicated coordination mode adopted by the ligand. Quantum chemical calculations provided data about structure, normal modes, charge distribution and delocalization. Glycine should act as a monodentate ligand through the oxygen of the carboxylate group in pentaaqua glycine aluminum(III). The other positions in the octahedral arrangement are occupied by coordinated water molecules.

FT-IR and FT-Raman spectroscopic signatures, vibrational assignments, NBO, NLO analysis and molecular docking study of 2-{[5-(adamantan-1-yl)-4-methyl-4H-1,2,4-triazol-3-yl]sulfanyl}-N,N-dimethylethanamine

FT-Raman and FT-IR spectra of the title compound 2-{[5-(adamantan-1-yl)-4-methyl-4H-1,2,4-triazol-3-yl]sulfanyl}-N,N-dimethylethanamine were recorded and investigated. The DFT/B3LYP/6-311++G(d,p) method was used to compute the vibrational wavenumbers. A good coherence between experimental and theoretical wavenumbers shows the preciseness of the assignments. NLO properties like the dipole moment, polarizability, first static hyperpolarizability, molecular electrostatic potential surface and contour map have been calculated to get a better cognizance of the properties of the title molecule. Natural bond orbital analysis has been applied to estimate the stability of the molecule arising from charge delocalization. The molecular docking studies concede that title compound may exhibit HIV-1 Protease 1N49 inhibitory activity.

An integrated experimental and theoretical investigation of the vibrational modes and molecular structure of a chelate, tetraaqua cysteine aluminum(III)

The complex formed by Al3+ and cysteine in aqueous solution has been studied by potentiometry, Raman spectroscopy and DFT calculations (DFT:B3LYP/6-311++G∗∗).Atomic charges, frontier molecular orbitals, electrostatic potential contour surface, electrostatic potential map and donor–acceptor second order perturbative energies were examined. The [Al(Cys)(H2O)4]2+ complex adopts a distorted octahedral geometry. Cysteine should act as a bidentate ligand through the oxygen of the carboxylate and the nitrogen of the amino group. The molecule has high HOMO–LUMO energy gap, intense intramolecular charge transfer and positive electrostatic potential.

Vibrational spectroscopic and DFT calculation studies of 2-amino-7-bromo-5-oxo-[1]benzopyrano [2,3-b]pyridine-3 carbonitrile

The vibrational spectra of 2-amino-7-bromo-5-oxo-[1]benzopyrano [2,3-b]pyridine-3 carbonitrile were recorded using fourier transform-infrared and fourier transform-Raman spectrometer. The optimized structural parameters, vibrational frequencies, Mulliken atomic charge distribution, frontier molecular orbitals, thermodynamic properties, temperature dependence of thermodynamic parameters, first order hyperpolarizability and natural bond orbital calculations of the molecule were performed using the Gaussian 09 program. The vibrational frequencies were assigned on the basis of potential energy distribution calculation using the VEDA 4.0 program. The calculated first order hyperpolarizability of ABOBPC molecule was obtained as 6.908×10−30 issue, which was 10.5 times greater than urea. The nonlinear optical activity of the molecule was also confirmed by the frontier molecular orbitals and natural bond orbital analysis. The frontier molecular orbitals analysis shows that the lower energy gap of the molecule, which leads to the higher value of first order hyperpolarizability. The natural bond orbital analysis indicates that the nonlinear optical activity of the molecule arises due to the π→π∗ transitions. The Mulliken atomic charge distribution confirms the presence of intramolecular charge transfer within the molecule. The reactive site of the molecule was predicted from the molecular electrostatic potential contour map. The values of thermo dynamic parameters were increasing with increasing temperature.

Rational design of carbonitrile-carboxaldehyde cation receptor models: probing the nature of the heteroatom-metal interaction.

In this work, hybrid functional and G4 methods were employed in the rational design of carbonitrile-carboxaldehyde receptor models for cation recognition. Electron-sharing and ionic interactions between the models and the cations were analyzed utilizing the concepts of overlap population, atomic valence, electrostatic potential, and CHELPG charge in order to elucidate the nature of the heteroatom-metal interaction, the N versus O disparity, and the effect of pH. Receptor fragment models from ionomycin were employed to rationalize the selection of receptor models for discriminating group I cations and enhancing the selectivity for Mg(II) rather than Ca(II), and to examine the effects of keto-enol forms and negatively charged sites. The changes in geometries, overlap population, metal valence, and CHELPG charge upon solvation in heptane medium as compared to the gas phase were negligible. The optimized geometries reveal that the interaction between group II cations and the keto, enol, and enolate forms of 2-cyanoethanal causes 12 % bending of the C-C-N angle from linearity. Overlap populations show that the electron-sharing interaction favors group II cations but that the same mechanism allows Li(I) to compete. The total spin of Li(I) is 17 % greater than that of Ca(II), but the G4 binding energies of the two are separated by more than 50 kcal/mol, favoring group II cations, which may eliminate interference from Li(I). 1,2-Dicyanoethylene, which has only one form, shows similar characteristics. CHELPG analysis shows that Mg(II) transfers 25 and 18 % of its positive charge to 2-cyanoethanal enolate and 1,2-dicyanoethylene, respectively. Hydrogen atoms receive most of the positive charge in both receptors, but the N-termini exhibit strikingly different characteristics. Electrostatic potential contour profiles were found to be in good agreement with the atomic charge distributions. The application of uncharged 1,3-dicarbonyl and 2-cyanocarbonyl receptors and a judicious choice of polymeric membrane that suppresses the Hofmeister effect should lead to high selectivity for magnesium, whereas the utilization of multiple negatively charged ionophores should result in selectivity for calcium.

Performance of metalloporphyrin malonic acids as dye sensitizers for use in dye-sensitized solar cells assessed by density functional theory

The performance of metallo (Zn, Cd, Hg) tetra (4-methylphenyl) porphyrin malonic acids as dye sensitizers for use in dye-sensitized solar cells (DSSCs) is assessed by means of ab initio molecular electronic structure calculations. The results reveal that malonic acid side chain cannot be described as an acceptor moiety, and the photo-to-current conversion efficiencies of the DSSCs that are based on organic semiconducting Cd and Hg tetra (4-methylphenyl) porphyrin malonic acid donors and a series of oxide semiconducting acceptors are expected to be greater than the reference porphyrin dye Zn tetra (4-methylphenyl) porphyrin malonic acid under standard global AM 1.5 solar conditions. This result is confirmed and characterized in terms of charge transfer, band gaps, density of states, polarizabilities, dipole moments, molecular electrostatic potential contours, electronic absorption energies, and infrared vibrational frequencies. The study emphasizes the role of metal centers, and provides alternatives to DSSCs with expensive materials.

Molecular geometry, conformational, vibrational spectroscopic, molecular orbital and Mulliken charge analysis of 2-acetoxybenzoic acid

The Fourier transform infrared (FT-IR) and FT-Raman spectra of 2-acetoxybenzoic acid (2ABA), a painkiller agent were recorded in the region 4000–450cm−1 and 5000–50cm−1 respectively. Hartree Fock (HF) and Density functional theory (DFT) methods have been used to determine its optimized geometrical parameter, atomic charges, and vibrational wavenumbers and intensity of the vibrational bands of the title molecule. The computed vibrational wave numbers were compared with the FT-IR and FT-Raman experimental data. The computational calculations were done at HF and DFT/B3LYP level with 6-311++G(d,p) basis set. The complete vibrational assignments were performed on the basis of the potential energy distribution (PED) analysis. The Mulliken charges, UV–Visible spectral analysis and HOMO–LUMO energy gap have been calculated and reported. The B3LYP method of calculated parameters is a good complement with the experimental findings. The thermodynamic properties like entropy, heat capacity and zero vibrational energy have been calculated and discussed. The electrostatic potential (ESP) contour surface and molecular electrostatic potential (MESP) of the molecule were constructed.

Quantum chemical study on influence of intermolecular hydrogen bonding on the geometry, the atomic charges and the vibrational dynamics of 2,6-dichlorobenzonitrile

FT-IR (4000–400cm−1) and FT-Raman (4000–200cm−1) spectral measurements on solid 2,6-dichlorobenzonitrile (2,6-DCBN) have been done. The molecular geometry, harmonic vibrational frequencies and bonding features in the ground state have been calculated by density functional theory at the B3LYP/6-311++G (d,p) level. A comparison between the calculated and the experimental results covering the molecular structure has been made. The assignments of the fundamental vibrational modes have been done on the basis of the potential energy distribution (PED). To investigate the influence of intermolecular hydrogen bonding on the geometry, the charge distribution and the vibrational spectrum of 2,6-DCBN; calculations have been done for the monomer as well as the tetramer. The intermolecular interaction energies corrected for basis set superposition error (BSSE) have been calculated using counterpoise method. Based on these results, the correlations between the vibrational modes and the structure of the tetramer have been discussed. Molecular electrostatic potential (MEP) contour map has been plotted in order to predict how different geometries could interact. The Natural Bond Orbital (NBO) analysis has been done for the chemical interpretation of hyperconjugative interactions and electron density transfer between occupied (bonding or lone pair) orbitals to unoccupied (antibonding or Rydberg) orbitals. UV spectrum was measured in methanol solution. The energies and oscillator strengths were calculated by Time Dependent Density Functional Theory (TD-DFT) and matched to the experimental findings. TD-DFT method has also been used for theoretically studying the hydrogen bonding dynamics by monitoring the spectral shifts of some characteristic vibrational modes involved in the formation of hydrogen bonds in the ground and the first excited state. The 13C nuclear magnetic resonance (NMR) chemical shifts of the molecule were calculated by the Gauge independent atomic orbital (GIAO) method and compared with experimental results. Standard thermodynamic functions have been obtained and changes in thermodynamic properties on going from monomer to tetramer have been presented.

Experimental and theoretical investigation of [Al(PCr)(H2O)] complex in aqueous solution

Phosphocreatine is a phosphorylated creatine molecule synthesized in the liver and transported to muscle cells where it is used for the temporary storage of energy. In Alzheimer’s disease, the capture of glucose by cells is impaired, which negatively affects the Krebs cycle, leading to problems with the generation of phosphocreatine. Furthermore, the creatine–phosphocreatine system, regulated by creatine kinase, is affected in the brains of Alzheimer’s disease patients. Aluminum ions are associated with Alzheimer’s disease. Al(III) decreases cell viability and increases the fluidity of the plasma membrane, profoundly altering cell morphology. In this study, one of the complexes formed by Al(III) and phosphocreatine in aqueous solution was investigated by potentiometry, 31P and 27Al NMR, Raman spectroscopy and density functional theory (DFT) calculations. The log KAlPCr value was 11.37±0.03. Phosphocreatine should act as a tridentate ligand in this complex. The 27Al NMR peak at 48.92ppm indicated a tetrahedral molecule. The fourth position in the arrangement was occupied by a coordinated water molecule. Raman spectroscopy, 31P NMR and DFT calculations (DFT:B3LYP/6-311++G**) indicated that the donor atoms are oxygen in the phosphate group, the nitrogen of the guanidine group and the oxygen of the carboxylate group. Mulliken charges, NBO charges, frontier molecular orbitals, electrostatic potential contour surfaces and mapped electrostatic potential were also examined.

Origin of Binding of Ammonia–Borane to Transition-Metal-Based Catalysts: An Insight from the Charge and Energy Decomposition Method ETS-NOCV

In the present study the bonding of ammonia–borane (AB) to selected transition-metal-based catalysts was studied on the basis of the charge and energy decomposition scheme ETS-NOCV. The following complexes of AB with mono- and bifunctional catalysts were considered: [Cp2Ti]2+ (I), [Pd(allyl)(2,4-hexadiene)]+ (II), [Pd(allyl)]+ (III), Ir(P2CH6)2]+ (IV), [Pd(PH3)2] (V), [Ni(NHC)2] (VI), [(POCOP)IrH2] (VII), [FeC8N2P2H22] (VIII), [RuC8N2P2H24] (IX), and [RuC19N5F3BO2H20]+ (X). ETS-NOCV allowed us to conclude that activation of X–H bonds (X = B, N) in AB occurs through different bonding mechanisms, starting from strong bonds based on typical σ donation from the occupied σ(B–H) orbital(s) to the metal (AB complexes I–IV) and σ-back-donation from the metal to the empty σ*(N–H) orbital of AB (complexes V and VI), going through hydrogen bonding, (AB)NH···N (VIII and IX), and ending up on untypical, weak π···HB(AB) and dihydrogen CH···HB(AB) interactions (X). Quantitative estimation of σ/π charge transfer contributions to the AB–catalyst bond explains the variation in the activation of B–H and N–H connections. Apart from the major components of the AB–catalyst bond, ETS-NOCV also revealed an important role of the secondary interactions XH−π (X = B, N) and BH···HN. The orbital interaction term ΔEorb, associated with the overall charge reorganization upon formation of AB–catalyst bonds, is less important than the electrostatic stabilization ΔEelstat. Furthermore, electrostatic stabilization appeared to be the major factor that controls the course of the reaction of AB with the catalysts; this term predominantly makes this reaction barrierless. Finally, the molecular electrostatic potential (MEP) contours allowed us to envisage that “electrophilic” catalysts will activate solely B–H bonds of AB, whereas complexes containing nucleophilic sites/areas should bind AB through the NH3 group. Finally, catalysts containing both electrophilic metal centers and, in close proximity, nucleophilic sites can simultaneously activate both the B–H and N–H bonds of AB.

Molecular structure of tetraaqua adenosine 5′-triphosphate aluminium(III) complex: A study involving Raman spectroscopy, theoretical DFT and potentiometry

The Alzheimer’s disease is one of the most common neurodegenerative diseases that affect elderly population, due to the formation of β-amyloid protein aggregate and several symptoms, especially progressive cognitive decline. The result is a decrease in capture of glucose by cells leading to obliteration, meddling in the Krebs cycle, the principal biochemical route to the energy production leading to a decline in the levels of adenosine 5′-triphosphate.Aluminium(III) is connected to Alzheimer’s and its ion provides raise fluidity of the plasma membrane, decrease cell viability and aggregation of amyloid plaques. Studies reveal that AlATP complex promotes the formation of reactive fibrils of β-amyloid protein and independent amyloidogenic peptides, suggesting the action of the complex as a chaperone in the role pathogenic process. In this research, one of complexes formed by Al(III) and adenosine 5′-triphosphate in aqueous solution is analyzed by potentiometry, Raman spectroscopy and ab initio calculations. The value of the logKAlATP found was 9.21±0.01 and adenosine 5′-triphosphate should act as a bidentate ligand in the complex. Raman spectroscopy and potentiometry indicate that donor atoms are the oxygen of the phosphate β and the oxygen of the phosphate γ, the terminal phosphates. Computational calculations using Density Functional Theory, with hybrid functions B3LYP and 6-311++G(d,p) basis set regarding water solvent effects, have confirmed the results. Frontier molecular orbitals, electrostatic potential contour surface, electrostatic potential mapped and Mulliken charges of the title molecule were also investigated.

Ab initio and nonempirical MODPOT/VRDDO calculations on drugs, carcinogens, suspected teratogens, and biomolecules

In this paper are presented our recent nonempirical ab initio MODPOT/VRDDO calculations on a variety of drugs and biomolecules: nucleic acid constituents, normal neurotransmitters and their metabolites, carcinogens and their activated metabolites, and attack of these on DNA constituents, and suspected teratogens. The MODPOT/VRDDO method incorporates two very desirable options into our own fast ab initio Gaussian programs: MODPOT-ab initio effective core model potentials and a charge-conserving integral prescreening approximation which we named vrddo (variable retention of diatomic differential overlap). For orbital energies and population analyses the MOD-POT/VRDDO results agree to essentially three decimal places with those of completely ab initio calculations with the same valence atomic basis set. Also included is a discussion of some molecular electrostatic potential contour maps, which in collaboration with Petrongolo were generated from previously calculated ab initio wave functions to illustrate comparisons of such maps from large basis set and minimal basis set ab initio calculations as well as from CNDO wave functions. Such maps allow a cogent comparison of pharmacophores in molecules that exert a similar pharmacological effect by the same mechanism. An example of such a comparison is discussed for electrostatic potential contour maps generated from our previous ab initio wave functions on morphine (a narcotic agonist) and nalorphine (a narcotic agonist-antagonist).

옥사졸의 양성자 친화도에 대한 DFT 연구

옥사졸 고리를 포함하는 lexitropsin에서, DNA minor groove의 구아닌-시토신 염기쌍의 구아닌과 수소결합을 형성하는데 중요 역할을 하는 옥사졸에 대해, 양성자화 될 때 가능한 두 가지 형태에 대해 DFT 계산을 통해 구조를 최적화시켰다. 최적화된 구조에 대해 B3LYP/6-31G* 수준에서 양성자 친화도를 계산하였다. 그 결과 옥사졸의 가능한 두 가지 형태 가운데 옥사졸의 질소 원자가 DNA minor groove 쪽으로 배향된 구조가 산소 원자가 minor groove 쪽으로 배향된 구조보다 양성자 친화도가 더 큼을 알 수 있었으며, 분자정전기 전위로 확인할 수 있었다. 아울러 양성자 친화도에 미치는 치환기 효과를 알아보기 위하여 여러 전자 주는 기와 전자 받는 기를 치환시켜 치환기 성질에 따른 양성자 친화도를 조사하였으며, 전자를 받는 기 보다 전자를 주는 기가 치환 되었을 때 양성자 친화도가 증가함을 알았다. The oxazole plays an important role in the binding of lexitropsin to the guanine-cytosine base pair from minor groove of DNA. The geometry optimization is performed with DFT calculations for the two possible conformations of the protonated oxazole. The proton affinities are calculated at B3LYP level of theory with 6-31G* basis set for the optimized geometry. It is found that the proton affinites of the conformations in which the oxazole nitrogen is the protonation center are greater than that of the conformations in which the oxazole oxygen is the protonation center. This result is in good agreement with molecular electrostatic potential (MEP) contour map. The proton affinities are also studied for various substituted oxazoles with the electron-donating and -withdrawing groups to estimate substitutent effect on the proton affinity at the hydrogen bonding site of the oxazoles. it is shown that the electron-donating substituents increase the proton affinity of oxazole, while the electron-withdrawing substituents decrease it.

Quaternary Structure of the Severe Acute Respiratory Syndrome (SARS) Coronavirus Main Protease

SARS (severe acute respiratory syndrome) has been one of the most severe viral infectious diseases last year and still remains as a highly risky public health problem around the world. Exploring the types of interactions responsible for structural stabilities of its component protein molecules constitutes one of the approaches to find a destabilization method for the virion particle. In this study, we performed a series of experiments to characterize the quaternary structure of the dimeric coronavirus main protease (M(pro), 3CL(pro)). By using the analytical ultracentrifuge, we demonstrated that the dimeric SARS coronavirus main protease exists as the major form in solution at protein concentration as low as 0.10 mg/mL at neutral pH. The enzyme started to dissociate at acidic and alkali pH values. Ionic strength has profound effect on the dimer stability indicating that the major force involved in the subunit association is ionic interactions. The effect of ionic strength on the protease molecule was reflected by the drastic change of electrostatic potential contour of the enzyme in the presence of NaCl. Analysis of the crystal structures indicated that the interfacial ionic interaction was attributed to the Arg-4...Glu-290 ion pair between the subunits. Detailed examination of the dimer-monomer equilibrium at different pH values reveals apparent pK(a) values of 8.0 +/- 0.2 and 5.0 +/- 0.1 for the Arg-4 and Glu-290, respectively. Mutation at these two positions reduces the association affinity between subunits, and the Glu-290 mutants had diminished enzyme activity. This information is useful in searching for substances that can intervene in the subunit association, which is attractive as a target to neutralize the virulence of SARS coronavirus.

Electrostatic potentials and fields from density expansions of deformed atoms in molecules.

The exact representation of the molecular density by means of atomic expansions, consisting in spherical harmonics times analytical radial factors, is employed for the calculation of electrostatic potentials, fields, and forces. The resulting procedure is equivalent to an atomic multipolar expansion in the long-range regions, but works with similar efficiency and accuracy in the short-range region, where multipolar expansions are not valid. The performances of this procedure are tested on the calculation of the electrostatic potential contour maps and electrostatic field flux lines of water and nitrobenzene, computed from high-quality molecular electron densities obtained with Slater basis sets.

The stability of peroxide ion O 22− at (110), (210) and (001) surfaces of MgO, CaO and SrO periodic ab initio calculations

The stability of peroxide ion O 2 2− resulting from the interaction between an adsorbed oxygen O and surface oxygen O 2− at the (110), (210) and (001) five layer surface films of the alkaline earth oxides MgO, CaO and SrO has been investigated using periodic density functional theory calculations. The 1:1 supercell model in which two incoming oxygens were added per each supercell, one at each side of the film, was employed in the calculations. The incoming oxygen/solid interaction energies exhibit exothermic character at the three considered films. The interaction energies at the fully relaxed surfaces increase monotonically from MgO to CaO to SrO, mainly from (110) to (210) to (001) planes, and are explainable in terms of the basicities and ionization potentials of the cations as well as the acceptor property of the incoming oxygen. Based on charge electron density maps, electrostatic potential contours and Mulliken population analysis the results confirm: (i) a genuine charge transfer from the surface to the adsorbed oxygen, (ii) the overlap population between the adsorbed oxygen and the surface oxygen is much larger than that between two oxygens in the crystal bulk, (iii) the overlap population between adsorbed oxygen and surface oxygen increases from MgO to CaO to SrO, being consistent with predicted order of stability of the peroxy bond.

Rationalizing the Strength of Hydrogen-Bonded Complexes. Ab Initio HF and DFT Studies

A comparative study of the relative stabilities of 17 multiply hydrogen-bonded complexes has been carried out using ab initio Hartree−Fock and density functional methods at the HF/6-311(d,p) and B3LYP/6-311(d,p) levels, respectively. Predicted hydrogen-bond geometries, relative stabilities, solvent and structural effects, and electrostatic potential contours are discussed in conjunction with experimental data. The B3LYP method, which secures a better agreement of the optimized geometries with the available X-ray data, has also been applied to calculate the gas-phase free energies and enthalpies. The computations reveal that the frequently used incremental approach, which takes into consideration the primary and secondary electrostatic interactions, can often be deceptive in interpreting the stabilities of the multiply hydrogen-bonded dimers. The explanation that reduced entropy enhances the stability of dimers involving intramolecular hydrogen bonds in their monomeric parts compared to similar structures lacking such bonds has also been found to be misleading. A comparison of the calculated results with available experimental stabilities measured in CHCl3 solutions shows that water present in the solvent may cause dramatic changes in relative stabilities. Electrostatic potential contours calculated at the B3LYP/6-311(d,p) level provide a useful qualitative explanation of the stability differences in the investigated complexes.

Two clusters of charged residues located in the electropositive face of the von Willebrand factor A1 domain are essential for heparin binding.

The VWF A1 domain seems to possess two heparin binding regions (residues 565-587 and 633-648) displaying positively charged amino acids, but the overall polyanion-A1 domain interaction scheme remains essentially elusive. To probe this molecular reaction as well as the role of electrostatic forces in VWF-heparin interaction, we performed mutagenesis and molecular modeling experiments. Fifteen mutated rVWFs were expressed [R571A, K572A, R573A, K585A, R571A/K572A/R573A, R578A/R579A, R578A/R579A/K585A, R571A/K572A/R573A/R578A/R579A/K585A (6A), K642G, K643G, K644G, K645G, K642G/K645G, K643G/K644G, and K642G/K643G/K644G/K645G (4G)]. Experimental results indicate that the multimeric structure of the mutants was similar to that of wild-type (WT) rVWF and that all rVWFs displayed normal binding to four conformation-dependent mAbs directed against the A1 domain. Three variants displayed significant reductions in the level of heparin binding. The 6A variant showed 39.2 +/- 1.3% of the WT rVWF level (p < 0.005), while mutants K643G/K644G and 4G showed 63.6 +/- 3.2 and 53.3 +/- 5% of the WT rVWF level, respectively (p < 0.005). Computational investigations showed that one face of the A1 domain is strongly electropositive, indicating that electrostatic forces should be essential in steering heparin onto its binding site. In agreement with our experimental data, the most striking alterations of the electrostatic potential contours were seen for mutants 4G, K643G/K644G, and 6A. Our data suggest that two clusters, one at positions 571-573, 578, 579, and 585 and the other at positions 642-645, act in concert for the recognition of heparin, forming a single extended binding surface across the electropositive face of the VWF A1 domain. A structural model of the VWF A1 domain-heparin complex is proposed, taking into account both experimental and computer modeling data.

Relationships between physicochemical properties and photoreactivity of four biorecalcitrant phenylurea herbicides in aqueous TiO2 suspension

The degradation of metobromuron (MB), isoproturon (IP), chlortoluron (CT), and chlorbromuron (CB) in heterogeneous photocatalytic solution via TiO2 was studied in detail. The influence of parameters such as TiO2 and herbicide concentration has been investigated and the optimal conditions for the abatement of the herbicides were found. The primary degradation of the herbicides was measured by HPLC analysis. A systematic study of their photodegradation has been made to assess structure–photoreactivity relationships. Correlation analysis showed that photoreactivity is associated with the molecular dipolar moment dependent on the differences in electronegativity of the substituents in the aromatic ring of each herbicide. The effect of the molecular charge distribution encoded in the dipolar moment was confirmed calculating electrostatic potential contour maps. It was also found that photoreactivity is inverse to the adsorption capability of these compounds on TiO2. Indeed, as confirmed in this paper, the extent of adsorption is not necessarily decisive in the evolution of the photochemical process and the photocatalytic reactions can occur independently of the degree of adsorption of the herbicides on TiO2.