Molecular Electrostatic Potential Distribution Research Articles

A Lanthanide Complex Fluorescent Probe for the Detection of Melamine.

Melamine has been illegally adulterated in dairy food because of the rich nitrogen content and stable chemical properties in recent years. Therefore, the detection of melamine is of great significance for food safety supervision and human health protection. As melamine is a weak fluorescent substance, it is difficult to detect melamine directly by fluorescence spectroscopy. In this work, we found that melamine can significantly enhance the emission of the tetracycline-europium (EuTC) complex at 616 nm. Therefore, we took EuTC complex as a fluorescent probe to detect melamine. According to the characterizations of absorption spectra, molecular electrostatic potential distribution, and the time-resolved spectra, we speculated that tetracycline and melamine may form a complex through hydrogen bonding interaction in the melamine-EuTC reaction system, causing the melamine closer approach to Eu3+ and reducing the non-radiative energy loss of water molecules to Eu3+, which significantly enhanced the fluorescence intensity of EuTC. The fluorescence intensity of EuTC complex with melamine concentration in the range of 0.5-40.0 μM shows a good linear relationship, and the correlation coefficient is 0.9951 with the detection limit of 7.85 × 10-8 M. It shows a high sensitivity for the EuTC complex as a fluorescent probe to detect melamine, which provides a supplement and extension for the detection of melamine by fluorescence spectroscopy.

Impact of Electrostatic Interaction on Bulk Morphology in Efficient Donor–Acceptor Photovoltaic Blends

AbstractBulk heterojunctions comprising mixed donor (D) and acceptor (A) materials have proven to be the most efficient device structures for organic photovoltaic (OPV) cells. The bulk morphology of such cells plays a key role in charge generation, recombination, and transport, thus determining the device performance. Although numerous studies have discussed the morphology‐performance relationship of these cells, the method of designing OPV materials with the desired morphology remains unclear. Herein, guided by molecular electrostatic potential distributions, we have established a connection between the chemical structure and bulk morphology. We show that the molecular orientation at the D‐A interface and the domain purity in the blend can be effectively modulated by modifying the functional groups. Enhancing the D‐A interaction is beneficial for charge generation. However, the resulting low domain purity and increased charge transfer ratio in its hybridization with the local excitation states lead to severe charge recombination. Fine‐tuning the bulk morphology can give balanced charge generation and recombination, which is crucial for further boosting the efficiency of the OPV cells.

Impact of Electrostatic Interaction on Bulk Morphology in Efficient Donor-Acceptor Photovoltaic Blends.

Bulk heterojunctions comprising mixed donor (D) and acceptor (A) materials have proven to be the most efficient device structures for organic photovoltaic (OPV) cells. The bulk morphology of such cells plays a key role in charge generation, recombination, and transport, thus determining the device performance. Although numerous studies have discussed the morphology-performance relationship of these cells, the method of designing OPV materials with the desired morphology remains unclear. Herein, guided by molecular electrostatic potential distributions, we have established a connection between the chemical structure and bulk morphology. We show that the molecular orientation at the D-A interface and the domain purity in the blend can be effectively modulated by modifying the functional groups. Enhancing the D-A interaction is beneficial for charge generation. However, the resulting low domain purity and increased charge transfer ratio in its hybridization with the local excitation states lead to severe charge recombination. Fine-tuning the bulk morphology can give balanced charge generation and recombination, which is crucial for further boosting the efficiency of the OPV cells.

Selective determination of epinephrine using electrochemical sensor based on ordered mesoporous carbon / nickel oxide nanocomposite

A nanocomposite of ordered mesoporous carbon/nickel oxide (OMC-NiO) was synthesized by hard-templating method. The nanocomposite remained ordered mesostructure and high surface area with the NiO nanocrystals embedded in the wall of the OMC. A sensitive sensor for electrochemical detection of epinephrine (EP) was developed with GCE modified by OMC-NiO nanocomposite. Cyclic voltammogram (CV) and differential pulse voltammetry (DPV) were used as the techniques to explore the electrochemical behavior of EP on OMC-NiO/GCE surface. The result showed that the electrode demonstrated better electrocatalytic performance to EP compared to that seen at OMC/GCE. Under the optimum condition, DPV measurements of the electrode response displayed a linear detection range for 8.0 × 10−7 to 5.0 × 10−5 M with a detection limit of 8.5 × 10−8 M (S/N = 3). It is worth noting that the electrocatalytic redox mechanism of EP on the electrode have studied through experiments and calculations (cyclic voltammetry and molecular electrostatic potential distribution). Moreover, the electrocatalytic behavior for the oxidation of EP and uric acid (UA) on OMC-NiO/GCE surface was investigated. The result showed that the sensor can be used to selectively determinate EP in the presence of an excesses of UA. Finally, the developed sensor was successfully applied to the determination of EP in spiked human blood serum and EP injection with satisfactory results.

Theoretical and infrared spectroscopy study of the structure of copper(II) poly-5-vinyltetrazolate and the products of its thermolysis

The structure of copper(II) poly-5-vinyltetrazolate and the products of its thermolysis has been studied by means of density functional theory and infrared spectroscopy. Copper(II) poly-5-vinyltetrazolate has been obtained and subsequently subjected to thermolysis. Infrared spectra of copper(II) poly-5-vinyltetrazolate and the products of its thermolysis have been recorded. The possible ways of coordination of copper(II) ions with tetrazole-containing ligands were established by analyzing the calculated molecular electrostatic potential distribution and comparing the calculated IR-spectra of the model structures to the experimental ones. It has been shown that the best agreement between the calculated and experimental data is observed for the model with three-coordinated copper(II) ions, which includes both the tetrazole-containing ligands coordinating two copper(II) ions through N(1)- and N(3)-atoms of the tetrazole ring, and the tetrazolecontaining ligands coordinating one copper(II) ion through either the N(2)- or the N(3)-atom. Recently we have shown that the product of thermolysis of copper(II) poly-5-vinyltetrazolate exhibits high catalytic activity in homocoupling of phenylacetylene and Huisgen [3 + 2]-cycloaddition. To establish the structure of the products of thermolysis of copper(II) poly-5-vinyltetrazolate, seven possible products have been proposed based on the analysis of the structure of copper(II) poly-5-vinyltetrazolate and the experimental IR-spectrum. IR-spectra of all proposed products have been calculated and the results of the calculations have been compared with the experimental IR-spectrum of copper(II) poly-5-vinyltetrazolate thermolysis product. It has been shown that the main product of thermolysis is cis-polycyanoacetylene.

Multimolecular Complexes of CL-20 with Nitropyrazole Derivatives: Geometric, Electronic Structure, and Stability.

The multimolecular complexes formed between 2,4,6,8,10,12-hexanitro-2,4,6,6,8,10,12-hexaazaisowurtzitane (CL-20) and nitropyrazole compounds were investigated using B3LYP-D3/6-311G(d,p) and B97-3c methods. CL-20 in these complexes was surrounded by methyl, nitro, and amino derivatives of 4-nitropyrazole. The influence of substituents on the molecular electrostatic potential distribution of nitropyrazoles was investigated to figure out the potential electrostatic interaction sites. For the complex, the O···H hydrogen bond was popular in the intermolecular interactions, and dispersion interaction played an essential role, especially in Cx/CL-20 multimolecular complexes. Trigger bond analysis showed that their strength increased upon the formation of intermolecular weak interactions. Nitro group charge calculations stated that the negative charge on almost all nitro groups showed a significant increase. Therefore, the sensitivity of CL-20 seemed to be lower than the original. In addition, the transfer of electron density between CL-20 and nitropyrzoles in complexes was investigated, revealing the influence of weak interactions on the electron density of CL-20.

Effect of Point Defect in Carbon Nanotube (8.0) on the Molecular Electrostatic Potential distribution Near it Edge

The influence of point defect on the electronic and spatial structure of carbon nanotubes (8.0) have been studied depending on the placement vacancies in the structure of nanotubes.
 On the basis of quantum-chemical calculations and using semi-empirical and ab initio approaches the maps of the distribution of molecular electrostatic potential were builds in the planes which are perpendicular to the main axis of the nanotubes. It is shown that defects such as vacancy, are placed outside the first hexagonal carbon belt no effect on the topology of the distribution of molecular electrostatic potential in the vicinity of the entrance to the carbon nanotube. Instead, reactivity of port’s atoms such nanotubes may determinated point defects of the vacancy type to be placed in first hexagonal belt.

Atomic insights into distinct hormonal activities of Bisphenol A analogues toward PPARγ and ERα receptors.

Bisphenol A analogues (BPAs) belong to a wide variety of large volume chemicals with diverse applications yet emerging environmental concerns. Limited experimental data have demonstrated that BPAs with different halogenation patterns distinctly affect the agonistic activities toward proliferator-activated receptor (PPAR)γ and estrogen receptors (ER)α. Understanding the modes of action of BPAs toward different receptors is essential, however, the underlying molecular mechanism is still poorly understood. Here we probed the molecular recognition process of halogenated BPAs including TBBPA, TCBPA, BPAF, BPC, triBBPA, diBBPA, and monoBBPA toward PPARγ and ERα by molecular modeling, especially the impact of different halogen patterns. Increasing bromination at phenolic rings of BPAs was found highly correlated with electrostatic interactions (R(2) = 0.978 and 0.865 toward PPARγ and ERα, respectively) and van der Waals interactions (R(2) = 0.995 and 0.994 toward PPARγ and ERα, respectively). More halogenated phenolic rings at 3,5-positions of BPAs increase the shielding of the hormonally active phenolic OH and markedly decrease electrostatic interactions favorable for agonistic activities toward PPARγ, but unfavorable for agonistic activities toward ERα. The halogenation at the phenolic rings of BPAs exerts more impact on molecular electrostatic potential distribution than halogenation at the bridging alkyl moiety. Different halogenations further alter hydrogen bond interactions of BPAs and induce conformational changes of PPARγ ligand binding domain (LBD) and ERα LBD, specifically affecting the stabilization of helix H12 attributable to the different agonistic activities. Our results indicate that structural variations in halogenation patterns result in different interactions of BPAs with PPARγ LBD and ERα LBD, potentially causing distinct agonistic/antagonistic toxic effects. The various halogenation patterns should be fully considered for the design of future environmentally benign chemicals with reduced toxicities and desired properties.

SERS and DFT investigation of 1-(2-pyridylazo)-2-naphthol and its metal complexes with Al(III), Mn(II), Fe(III), Cu(II), Zn(II) and Pb(II)

The development of surface-enhanced Raman scattering (SERS) as a prospective analytical methodology for detection of metal ions was shown in recent years by several studies on metal complexes. In this work, 1-(2-pyridylazo)-2-naphthol (PAN) and its Al(III), Mn(II), Fe(III), Cu(II), Zn(II) and Pb(II) complexes were studied by FTIR, FT-Raman and surface enhanced Raman spectroscopies. Molecular geometry optimization, molecular electrostatic potential (MEP) distribution and vibrational frequencies calculations were performed using the hybrid B3LYP exchange-correlation functional for the PAN molecule and its bidentate complexes. The calculated MEP distributions indicated the atoms with highest electronegativity, the adsorption to the silver surface occurring through these atoms. Based on experimental and theoretical data we were able to identify unique and representative features, useful for the identification of each PAN-metal complex.

A New Method for Mapping the Molecular Surface of a Protein Structure Using a Spherical Self-Organizing Map.

A spherical self-organizing map (SSOM) was applied for mapping the molecular surface of a protein structure on a spherical structure. The active site of the X-ray crystal structure of β2 receptor protein was used for this purpose. After mapping the molecular surface points and assigning the associated molecular electrostatic potential (MEP) values, the original 3D structure of the active site was well reproduced by the SSOM. In order to validate the geometrical transformation and the resulting MEP distribution, the molecular surfaces of twenty β2 ligands were mapped on the established SSOM sphere. The MEP values of two spheres derived from the ligand and the β2 receptor protein were compared. In almost all cases of strong ligands, the two spheres had a moderate negative correlation.

MOLECULAR TAILORING APPROACH: TOWARDS PC-BASED AB INITIO TREATMENT OF LARGE MOLECULES

The development of a fragmentation-based scheme, viz. molecular tailoring approach (MTA) for ab initio computation of one-electron properties and geometry optimization is described. One-electron properties such as the molecular electrostatic potential (MESP), molecular electron density (MED), and dipole moments are computed by synthesizing the density matrix (DM) of the parent molecule from DMs of its small overlapping fragments. The electron density obtained via MTA was found to be typically within 0.5% of its actual counterpart, while maximum errors of about 2% were noticed in the case of the dipole moment and MESP distribution. An attempt is made to develop MTA-based geometry optimization that involves picking relevant energy gradients from fragment self-consistent field (SCF) calculations, bypassing the CPU and memory extensive SCF step of the complete molecule. This is based on the observation that the MTA gradients mimic the actual ones fairly well. As the calculations on individual fragments are mutually independent, this algorithm is amenable to large-scale parallelization and has been extended to a distributed setup of PCs. The code developed is put to test on γ-cyclodextrin, taxol, and a small albumin-binding protein (1prb) for one-electron properties. Further, molecules such as γ-cyclodextrin, taxol, a silicalite, and 1prb are subjected to MTA-based geometry optimization, on a PC cluster. The results indicate a favorable speedup of two to three times over the actual computations in the initial phase of optimization. Furthermore, it enables computations otherwise not possible on a PC. Preliminary results indicate similar savings with sustained accuracy even for large molecules at the level of Møller–Plesset second order perturbation (MP2) theory.

Structural analogues of reactive intermediates as inhibitors of glucosamine-6-phosphate synthase and phosphoglucose isomerase

The active centers of phosphoglucose isomerase (PGI) and the hexose phosphate isomerase domain (HPI) of glucosamine-6-P (GlcN-6-P) synthase demonstrate apparent similarity in spatial arrangement of critical amino acid residues, except Arg272 of the former and Lys603 and Lys485 of the latter. Ten derivatives of d-hexitol-6-P, 5-phosphoarabinoate, or 6-phosphogluconate, structural analogues of putative cis-enolamine or cis-enolate intermediates, were tested as inhibitors of fungal GlcN-6-P synthase and PGI. None of the investigated compounds demonstrated equally high inhibitory potential against both enzymes. 2-Amino-2-deoxy-D-mannitol 6-P was found to be the strongest GlcN-6-P synthase inhibitor in the series, with an inhibition constant equal to 9.0 (±1.0) × 10 −6 M. On the contrary, 5-phosphoarabinoate (5PA) exhibited specificity for PGI, with K i = 2.2 (±0.1) × 10 −6 M. N-acetylation substantially lowered the GlcN-6-P synthase inhibitory potential of 2-amino-2-deoxy- d-glucitol-6-P but strongly enhanced inhibitory potential of this compound towards PGI. Molecular modeling studies revealed that interactions of the C1–C2 part of transition state analogue inhibitors with the respective areas demonstrating different distribution of molecular electrostatic potential (MEP) inside HPI and PGI active centers determined enzyme:ligand affinity. In Escherichia coli HPI, a patch of the negative potential created by Glu488 aided by Val399, supposed to stabilize a putative positively charged intermediate, especially attracts ligands containing 2-amino function. The Arg272, Lys210, and Gly271 peptide bond nitrogen system, present in the corresponding space of rabbit PGI, creates an area of positive MEP, stabilizing cis-enolate intermediate and attracting its structural mimics, such as 5PA.

Electronic properties of Strandberg anions: A DFT study of [X2Mo5O23]n−, (X = PV, SVI, AsV, SeVI), and [(RP)2Mo5O21]4− (R = H, CH3, C2H5)

The electronic properties of the anions mentioned in the title polyanions were calculated by means of Density Functional Theory (DFT). The redox properties and the basicity of the external oxygen sites of those polyanions were analyzed. The results show that the redox properties of Strandberg anions depend on the nature of heteroatom X. The organic group bonded to the heteroatom modifies the redox property of the cluster. The oxygen basicities of the polyanions were analyzed by virtue of molecular electrostatic potential (MEP). The MEP distribution suggests that the most basic centers are triple-bridging oxygen atoms, one of which is shared with two metal atoms and one heteroatom X in [P2Mo5O23]6− and [As2Mo5O23]6−. In [(RP)2Mo5O21]4−, the triple-bridging oxygen atoms and the double-bridging oxygen atoms bonded to two Mo atoms identified as the most basic centers. © 2005 Wiley Periodicals, Inc. Int J Quantum Chem, 2005

A combined use of global and local approaches in 3D-QSAR

A new methodology for 3D-QSAR studies, based on the combined use of global and local approaches, is proposed. Information on the whole molecular electrostatic potential distribution is obtained from a global approach and used to build global models, based on the grid weighted holistic invariant molecular (G-WHIM) descriptors, as well as to define an alignment criterion for developing local models. Moreover, a new technique based on local correlation indexes is proposed to perform the variable reduction. Both the global and the local models are obtained by a variable selection genetic algorithms technique. The methodology is applied to a benchmark steroid data set. The molecular electrostatic potential and the experimental binding affinity constants for the corticosteroid-binding globulin are used as variables. The QSAR models obtained compared with those obtained by the CoMFA method show higher predictive ability and give insight into the local molecular features that determine high binding affinity.

Design and synthesis of nonpeptide angiotensin II receptor antagonists featuring acyclic imidazole-mimicking structural units

Extensive molecular modelling studies, including conformational analysis and the comparison of molecular electrostatic potential distributions, were used to evaluate structural parameters of new antagonists containing acyclic replacements of the N=C-N imidazole region. The synthesis and the biological screening of a series of acyl biphenyltetrazole derivatives were planned and realized to gain an insight into the structure–activity relationships of this unusual class of Angiotensin II antagonists.

Crystal and Molecular Structure of 4-[ω-(Benzotriazolyl)alkyl]-1-(2-methoxyphenyl)piperazines with a Different Pharmacological Activity

The crystal structure of six 4-[ω-(benzotriazolyl)alkyl]-1-(2-methoxyphenyl)piperazine hydrochlorides 1-6 with a similar in vitro but different in vivo activity has been solved. A conformational analysis of free bases by Random Search and AM1 methods has been performed. Molecular electrostatic potential distribution (MEP) and dipole moments for the optimized crystallographic structures and global energy minimum conformations were calculated. Crystallographic data, as well as the conformational analysis indicated that the investigated compounds can adopt a variety of conformations of small energy difference. The effect of conformational changes on MEP was discussed.

Comparison of electrostatic similarity approaches applied to a series of ketanserin analogues with 5-HT2A antagonistic activity

Similarities between the molecular electrostatic potential (MEP) distributions of a series of analogues of ketanserin were studied using the MEPSIM package with the aim of correlating MEP patterns with the binding affinities for the 5-HT2A receptor. This study was also used to assess different approaches that can be used in this kind of similarity studies. The best correlation between MEP distributions and biological activities was found when only negative electrostatic potentials were taken into account, while the consideration of the whole MEP distribution produced a classification of the compounds than was mainly steric and not related with their biological activities. The two structural features of the considered molecules that generated negative MEP zones and consequently that could be related with their recognition by the 5-HT2A receptor, were the lone pairs of a carbonyl oxygen and the π-system of an aromatic ring.

Suitability of density functional methods for calculation of electrostatic properties

A systematic analysis was performed on the suitability of the molecular electrostatic potential (MEP) and MEP-derived properties determined by means of density functional (DFT) methods. Attention was paid to the electrostatic potential (ESP) derived charges, the ESP and exact quantum mechanical dipole moments, the depth of MEP minima, and the MEP distribution in layers around the molecule for a large series of molecules. The electrostatic properties were determined at either local or nonlocal DFT levels using different functionals. The results were compared with the values estimated from quantum mechanical calculations performed at Hartree–Fock, Møller–Plesset up to fourth order, and CIPSI levels. The suitability of the MEP-derived properties estimated from DFT methods is discussed for application in different areas of chemical interest. © 1997 John Wiley & Sons, Inc. J Comput Chem 18: 980–991, 1997

Three-dimensional modelling of human cytochrome P450 1A2 and its interaction with caffeine and MeIQ.

The three-dimensional modelling of proteins is a useful tool to fill the gap between the number of sequenced proteins and the number of experimentally known 3D structures. However, when the degree of homology between the protein and the available 3D templates is low, model building becomes a difficult task and the reliability of the results depends critically on the correctness of the sequence alignment. For this reason, we have undertaken the modelling of human cytochrome P450 1A2 starting by a careful analysis of several sequence alignment strategies (multiple sequence alignments and the TOPITS threading technique). The best results were obtained using TOPITS followed by a manual refinement to avoid unlikely gaps. Because TOPITS uses secondary structure predictions, several methods that are available for this purpose (Levin, Gibrat, DPM, NnPredict, PHD, SOPM and NNSP) have also been evaluated on cytochromes P450 with known 3D structures. More reliable predictions on alpha-helices have been obtained with PHD, which is the method implemented in TOPITS. Thus, a 3D model for human cytochrome P450 1A2 has been built using the known crystal coordinates of P450 BM3 as the template. The model was refined using molecular mechanics computations. The model obtained shows a consistent location of the substrate recognition segments previously postulated for the CYP2 family members. The interaction of caffeine and a carcinogenic aromatic amine (MeIQ), which are characteristic P450 1A2 substrates, has been investigated. The substrates were solvated taking into account their molecular electrostatic potential distributions. The docking of the solvated substrates in the active site of the model was explored with the AUTODOCK programme, followed by molecular mechanics optimisation of the most interesting complexes. Stable complexes were obtained that could explain the oxidation of the considered substrates by cytochrome P450 1A2 and could offer an insight into the role played by water molecules.

Derivation of fused-sphere molecular surfaces from properties of the electrostatic potential distribution

The distribution of molecular electrostatic potential (MEP) on a surface is a common model used to describe simultaneously steric properties (e.g., size, shape) and reactive properties (e.g., electro- and nucleophilic positions) of a molecule. In this work, we analyze some relations between these two properties. In particular, we explore the possible definition of an optimum fused-sphere molecular surface from properties of the MEP distribution. With this goal, we study how several statistical descriptors of the two-dimensional MEP distribution change upon shrinking or enlarging a van der Waals surface. We find that some of the descriptors exhibit critical points in terms of a scaling factor. We use this property to define effective atomic radii. In particular, we find that a reasonable molecular envelope is defined as the surface having the lowest (i.e., most negative) average negative MEP, with the largest possible dispersion about the mean. We discuss the resulting atomic radii and compare them with others in the literature derived from only steric considerations. The present results expand the scope of fused-sphere surfaces for modeling microscopic or structural molecular properties. © 1996 by John Wiley & Sons, Inc.