Molecular similarity based on atomic electrostatic potential

We propose a new similarity measure operating in the space spanned by the potential values, evaluated at atoms constituting the benzene ring and the COOH group in para-substituted benzoic acids and at benzene ring atoms in monosubstituted benzenes. The similarity measures are equivalent to the Euclidean distance between points in that space. Only the distances between the potentials at corresponding atoms in different molecules are included. The distances for benzene rings were very similar, regardless of whether they were calculated in para-substituted acids or in monosubstituted benzenes. As reference reactions, dissociation of benzoic acids and nitration of monosubstituted benzenes have been used. The effects of reduction of dimensionality of the potential space on the comparison of similarity measures with the free energies of the reference reactions have been investigated. It became obvious that the potentials at individual atoms in molecules of the acids and monosubstituted benzenes are mutually correlated to a high degree.     

Molecular electrostatic potential on the surface envelopes of macromolecules: B-DNA

A procedure for calculating the molecular electrostatic potentials on surface envelopes surrounding macromolecules is presented. This new representation of potential is employed in studying B-DNA double helices and, from the results, deductions are drawn on the interaction specificities of B-DNA with electrophiles.     

Molecular electrostatic potential devices on graphite and silicon surfaces

We demonstrate that molecular gates using molecular electrostatic potentials (MEP) can be used on hydrogen-passivated silicon substrates without any disturbance of their behavior in vacuum; however, the use of graphite as a substrate strongly affects such behavior. As expected, the substrate may become one more design variable. The ability to have several substrate alternatives is very important for the practical implementation of this new scenario based on molecular potentials. In general, the effect of the substrate can be predetermined by calculating the MEP of the surface as this indicates how strongly its intrinsic potential is.     

芬太尼类化合物的分子静电势研究

本文应用INDO波函数计算了三个芬太尼类化合物的分子静电势。酰胺氧原子周围均存在一个势阱很深的宽广的负电势区域, 是最重要的负电中心。 哌啶环4-位引入甲氧甲基后,增加了新的负电势区域。哌啶环1-位芳环周围具有宽广的正电势区域。 哌啶氮原子和酰胺氮原子附近存在较小的负电势区域。 基于计算出的静电势推测了三个化合物的镇痛作用的可能机理及药物结构与毒性的关系。     

Synthesis and characterization of potential impurities of Oxcarbazepine drug substance: An antiepileptic agent

Oxcarbazepine is a drug substance used to treat epilepsy. During its bulk synthesis of various impurities formation will be observed. Herein we describe the formation, synthesis and characterization of four potential impurities, namely, N-acetyl Oxcarbazepine, N-formyl Oxcarbazepine, N-carbamoyl Oxcarbazepine, and Oxcarbazepine dimer. These impurities are listed in several Pharmacopoeias and the control of these impurities below the threshold level is essential. Our study will be a guide for making these reference standards.     

Molecular electrostatic charge models: A topographical approach

Electrostatic charge models for molecules have been developed by employing the critical topographical features of the molecular electrostatic potential (MESP ) as the “fitting” criterion. These models include one or more spherical Gaussians for incorporating the continuous electron-charge distribution in addition to the positive valued point charges representing the nuclei. The model parameters (point charges, the orbital exponents, and Gaussian centers) are optimized so as to mimic the extremal characteristics of the corresponding quantum chemical MESP . The test cases reported here include methane, ethylene, and methanol molecules. The charge models developed using the present method are seen to satisfactorily reproduce the ab initio MESP and its extremal features. © 1994 John Wiley & Sons, Inc.     

Tautomerism of the antiepileptic drug Felbamate: A DFT study

The Felbamate is a novel anticonvulsant and neuropathic pain drug that can exist as three possible tautomers. Herein, employing density functional theory (DFT) and handling the solvent effects with the PCM model, the structural parameters, energy behavior, natural bond orbital analysis (NBO), as well as the tautomerism of Felbamate are investigated. F1 is the kinetically and thermodynamically most stable tautomer of Felbamate, which contains the amide group in each of the carbamate moieties. The calculated NMR chemical shifts and IR vibrational frequencies are in good agreement with the experimental values, confirming the suitability of the optimized geometry for Felbamate. The tautomerization reaction of F1 to each of the other tautomers occurs via an intramolecular proton transfer. This reaction affects considerably the structural parameters and atomic charges of the Felbamate molecule. A large HOMO-LUMO energy gap implies a high stability of the F1 tautomer.     

Molecular electrostatic potential approach to determining the steric effect of phosphine ligands in organometallic chemistry

A two-layer ONIOM(B3LYP/6-31G(d,p):UFF) quantum mechanics (QM)-molecular mechanics (MM) optimization of PR3 ligands, where the QM layer is always constructed as PH3, followed by molecular electrostatic potential (MESP) analysis of the QM layer is suggested as a simple and effective method for evaluating the steric effect of PR3 ligands. The subtle variations in the electron distribution that arise as a result of the steric bulkiness as well as the conformational changes in the substituent groups is well reflected in the value of the MESP minimum (Vmin) located in the QM region. In general, a sterically bulky group has always shown a more negative Vmin than a sterically less bulky group. The difference between the Vmin value of free PH3 and the Vmin value at the QM region of PR3 is used as a measure of the steric effect of the PR3 ligand. This value, designated as MESPsteric, showed a good linear correlation with the cone angle values as well as the average of the intervalence HPH angles found in the QM layer. Further, the difference between the Vmin value at the QM region of PR3 (an indicator of the steric effect) and the Vmin value of the completely optimized PR3 ligand (an indicator of the combined effect of steric and electronic effects) showed a good linear correlation with the Hammett Sigmasigmap constants, which further confirmed the present approach to understanding the steric effect separately from the electronic effect.     

富勒烯C72分子静电势以及Sc2@C72的理论研究

已制备出来的富勒烯都遵循分离五元环规则(IPR)。C72虽然满足五元环分离规则具有D6d对称结构,然而迄今为止还没有实现其宏观量的合成,人们称之为“遗失的碳笼”。但人们合成出了内掺金属M@C72(M=Ca,La等),证实了C72的存在[1-4]。最近用两步高性能液体色谱方法又成功地分离出La2     

Molecular electrostatic fields from bond fragments

We apply completely transferable, strictly localized molecular orbitals for the calculation of molecular electrostatic fields. This approach, derived from our previous bond fragment method for the calculation of molecular electrostatic potentials, reduces computational efforts drastically. The fields around small molecules containing first- and second-row atoms are systematically overestimated as compared with ab initio calculations with a minimal STO -3G basis set. However, deviations can be corrected by a simple multiplicative factor, which means that the overall shape of the potential and field around the molecule is correctly reproduced. Our approximate field can be used to determine possible hydration sites around molecules as proposed earlier by Peinel and coworkers. Application of the method is illustrated on the formamide molecule.     

Theoretical studies of the mechanism of the action of the neurohypophyseal hormones. I. Molecular electrostatic potential (MEP) and molecular electrostatic field (MEF) maps of some vasopressin analogues

Summary Continuing our theoretical studies of the oxytocin and vasopressin analogues, we have analysed the molecular electrostatic potential (MEP) and the norm of the molecular electrostatic field (MEF) of [1--mercaptopropionic acid]-arginine-vasopressin ([Mpa¹]-AVP), [1-(-mercapto-,-cyclopentamethylene)propionic acid]-arginine-vasopressin ([Cpp]-AVP), and [1-thiosalicylic acid]-arginine-vasopressin ([Ths]-AVP) whose low-energy conformations were calculated in our previous work. These compounds are known from experiment to exhibit different biological activity. The scalar fields mentioned determine the energy of interaction with either charged (MEP) or polar (MEF) species, the energy being in the second case either optimal or Boltzmann-averaged over all the possible orientations of the dipole moment versus the electrostatic field. The electrostatic interactions slowly vanish with distance and can therefore be considered to be the factor determining the molecular shape at greater distances, which can help in both predicting the interactions with the receptor at the stage of remote recognition and in finding the preferred directions of solvation by a polar solvent. In the analysis of the fields three techniques have been used: (i) the construction of maps in certain planes; (ii) the construction of maps on spheres centered in the charge center of the molecule under study and of poles chosen according to the main axes of the quadrupole moment; and (iii) the construction of surfaces corresponding to a given value of potential. The results obtained show that the shapes of both MEP and MEF are similar in the case of [Mpa¹]-AVP and [Cpp¹-AVP (biologically active), while some differences emerge when comparing these compounds with [Ths¹]-AVP (inactive). It has also been found that both MEP and MEF depend even more strongly on conformation.     

Computational studies on the doped graphene quantum dots as potential carriers in drug delivery systems for isoniazid drug

In this study, the application of graphene quantum dots (GQDs) and doped GQDs as potential carriers for the delivery of isoniazid (Iso) drug has been investigated, using density functional theory (DFT) calculations. For this purpose, the hexa-peri-hexabenzocoronene (as a GQD model) and its BN-, BP-, AlN-, and AlP-doped (C₃₆X₃Y₃H₁₈ where X = B, Al and Y = N, P) forms were selected. Our results indicated that the adsorption energies of isoniazid on doped GQDs were more negative than that of pure GQD. Moreover, the calculations showed that adsorption of isoniazid on AlN- and AlP-doped GQDs was thermodynamically favorable. The dipole moments of BP-, AlN-, and AlP-doped GQDs were much greater (5.799, 1.860, and 3.312 D, respectively) than that of pristine GQD (0 D). The AlN-Iso and AlP-Iso complexes had small energy gaps, low chemical potentials, and low global hardnesses, which were appropriate for their attachments to the target site. The nature of interactions was analyzed by the quantum theory of atoms in molecules (QTAIM) and noncovalent interaction (NCI) analyses. Overall, the results confirmed that the AlN- and AlP-doped GQDs could be used as potential carriers for drug delivery application.     

Molecular insight into the electrostatic membrane surface potential by 14n/31p MAS NMR spectroscopy: nociceptin-lipid association

Exploiting naturally abundant (14)N and (31)P nuclei by high-resolution MAS NMR (magic angle spinning nuclear magnetic resonance) provides a molecular view of the electrostatic potential present at the surface of biological model membranes, the electrostatic charge distribution across the membrane interface, and changes that occur upon peptide association. The spectral resolution in (31)P and (14)N MAS NMR spectra is sufficient to probe directly the negatively charged phosphate and positively charged choline segment of the electrostatic P(-)-O-CH(2)-CH(2)-N(+)(CH(3))(3) headgroup dipole of zwitterionic DMPC (dimyristoylphosphatidylcholine) in mixed-lipid systems. The isotropic shifts report on the size of the potential existing at the phosphate and ammonium group within the lipid headgroup while the chemical shielding anisotropy ((31)P) and anisotropic quadrupolar interaction ((14)N) characterize changes in headgroup orientation in response to surface potential. The (31)P/(14)N isotropic chemical shifts for DMPC show opposing systematic changes in response to changing membrane potential, reflecting the size of the electrostatic potential at opposing ends of the P(-)-N(+) dipole. The orientational response of the DMPC lipid headgroup to electrostatic surface variations is visible in the anisotropic features of (14)N and (31)P NMR spectra. These features are analyzed in terms of a modified "molecular voltmeter" model, with changes in dynamic averaging reflecting the tilt of the C(beta)-N(+)(CH)(3) choline and PO(4)(-) segment. These properties have been exploited to characterize the changes in surface potential upon the binding of nociceptin to negatively charged membranes, a process assumed to proceed its agonistic binding to its opoid G-protein coupled receptor.     

Multipole expansions of the electrostatic molecular potential

Multipole expansions of the electrostatic molecular potential up to the hexadecapole terms are examined for H₂O, NH₃ and C₂H₄NH. A reasonable approximation to get unexpensive first order representations of the electrostatic potential for regions outside the van der Waals volume is found.     

Molecular electrostatic potentials from PCILO wave functions

The molecular electrostatic potentials for several small molecules were investigated using PCILO wave functions at different stages of the perturbation expansion. The utility of the localized picture within the PCILO framework can be shown, even at zeroth order only. For simplicity the approximation of fixed standard bond polarities could be introduced in order to reproduce shape and values of the potential with a sufficient degree of accuracy.