Molecular Moment Research Articles

A study of ring‐substituent influence on pharmacological activity in a series of phenethylamine‐type psychedelics

AbstractGeometry optimization for each member of a series of 15 substituted phenethylamines with reported psychotomimetic activity was performed using MM2 and MOPAC93 (AM1) methods. This was followed by calculation of previously developed, numerically unitary structure indices, viz., the molecular transform indices FTm, FTe, and FTc, indicating general, electronic, and charge properties respectively, and the analogous normalized molecular moment indices Mn, Me, and Mc. Each of the indices was used independently with the pharmacological data in a procedure to generate clusters containing three or more data points; linear correlations within each cluster were then determined. The Mn index performed best under the criteria, giving three clusters containing a total of 10 compounds; the other indices gave clusters accounting for totals of five to eight compounds for each index. Analysis of the clusters indicated that the 2‐ and 5‐positions on the phenyl ring should have substituents and that substitution at the 4‐position, preferably with a halogen, methyl, or thioether group, was critical for maximum pharmacological activity. The latter results suggest that ease of metabolic hydroxylation at the 4‐phenyl position (or the substituent group at that position, e.g., methyl, ethyl, etc.) is necessary for maximum activity. The performance of the Mn index appears to indicate more of a dependence on 3D spatial requirements for bioactivity, with molecular electronic and charge properties, respectively, being of secondary importance. Further, clustering and correlation regression of the biological data on the calculated logarithm of the octanol/water partition coefficient (CLogP) showed that the latter may be an important factor influencing pharmacological activity in this series. © 2004 Wiley Periodicals, Inc. Int J Quantum Chem, 2004

Dielectric tensor and optical spectra of quaterthiophene crystals

We present an approach to the microscopic calculation of the dielectric tensor near the resonances of mechanical Frenkel excitons in a vibronic coupling regime with one effective mode. The model, applied to the prototypical quaterthiophene crystal, is based on a discrete distribution of charges for the evaluation of the molecular transition moment, whilst the coulombic interactions responsible for the exciton delocalization in the crystal are calculated by the Ewald method. From the calculated tensor we simulate absorbance and reflectance spectra and by a direct comparison with the experimental ones, we identify the origin of some shoulders present in the spectra.

Enhanced Molecular Multipole Moments and Solvent Structure in Supercritical Carbon Dioxide

Understanding the green solvent: The solvent structure and molecular electrostatic multipole moments of supercritical carbon dioxide (scCO2) were studied using ab initio molecular dynamics simulations. Blue, cyan, and orange (see graphic) represent the increasing probability of finding an oxygen atom, which belongs to a neighboring molecule, in the first coordination shell of CO2.

Atomic Charges Are Measurable Quantum Expectation Values: A Rebuttal of Criticisms of QTAIM Charges

The charge on an atom in a molecule is defined by the quantum theory of atoms in molecules (QTAIM) as the expectation value of the number operator, a Dirac observable. An atomic charge is measurable and it, together with its change, contributes to numerous measurable properties: to all molecular moments, to molecular polarizability, to intensities of electronic, infrared, and Raman absorption intensities, and to the polarization of a dielectric. The properties resulting from an applied magnetic field parallel those induced by an electric field, with the induced atomic charge being replaced by the atomic current. The phenomena of polarization and magnetization, permanent or induced, have a common physical basis when described in terms of the physics of an open system, all expressions exhibiting a single underlying structure in terms of their atomic contributions. The paper points out that this physics and the appeal the experiment it affords are lost when one employs other definitions of an atomic charge.

Magnetic properties of the R2T13.6Si3.4 single crystals (R = U, Lu; T = Fe, Co)

The magnetization study was performed on single crystals of uranium intermetallic compounds R2T13.6Si3.4 (R=U, Lu; T=Fe, Co). A very different behavior of the U sublattice was observed for T=Fe and Co. In U2Fe13.6Si3.4, the U sublattice is magnetic and contributes a lot to the exchange and anisotropy energies whereas in U2Co13.6Si3.4 it is presumably non-magnetic. Influence of U in the latter case consists in reduction of the Co magnetic moments and exchange interaction between them, which causes a much lower molecular magnetic moment and Curie temperature in U2Co13.6Si3.4 compared to Lu2Co13.6Si3.4.

Ab InitioQuality Electrostatic Atomic and Molecular Properties Including Intermolecular Energies from a Transferable Theoretical Pseudoatom Databank

The development of a theoretical databank of transferable pseudoatoms for fast prediction of the electron densities and related electronic properties of proteins is described. Chemically unique pseudoatoms identified on the basis of common connectivity and bonding are extracted from ab initio molecular densities of a large number of small molecules using a least-squares projection technique in Fourier transform space. The performance of the databank is evaluated by comparison of the electron densities and electrostatic properties of the amino acids GLN, SER, and LEU and their dimers with those obtained from molecular calculations on the same test compounds. It is found that deformation density bond peaks are reproduced to within 0.02−0.10 e/A3, whereas electrostatic potentials, bond critical point indices, atomic charges, and molecular moments show differences with results from calculations performed directly on the test molecules which are comparable with or smaller than the spread of the values between ...

A Model for the Chemical Bond

A simple model of the chemical bond is developed on the basis of an elementary MO theory requiring solution of at most a 2 × 2 Hückel secular equation including overlap. The fundamental quantities are the atomic integrals α1 and α2 giving the energies of the isolated atoms or ions, and the bond integral b which depends on the overlap S between the interacting AOs. For homonuclear diatomics, the interaction is first order in b, and the bond is formed as long as the number of electrons in bonding MOs is greater than the number of electrons in antibonding MOs. When the number of bonding electrons equals the number of antibonding electrons Pauli repulsion occurs, provided overlap between the interacting AOs is explicitly considered. Model bond energies with |β| « 60 kcal mol–1 and |βπ| « 55 kcal mol–1 reproduce experimental atomization energy results for σ- and π-electrons of most first-row homonuclear diatomics with an average error not exceeding 10%. Bond stereochemistry is introduced in terms of bond energy maximization. Symmetry arguments are used to reduce consideration of CH4 to a set of 2 × 2 secular equations, whose best energy corresponds to the tetrahedral arrangement of four straight CH bonds, explaining in a natural way the formation of four equivalent sp3 hybrids on carbon. Next, electron distribution in a two-electron bond is considered, and atomic, overlap, gross atomic, and formal charges are introduced to explain the origin of molecular electric moments.

Symmetry of van der Waals molecular shape and melting points of organic compounds

Long-known empirical regularities in melting points (mp) among molecular crystals of organic compounds with a closely related stoichiometry are dictated by a short-range molecular van der Waals term in their crystal field. This term, which acts as a symmetry-breaking perturbation on the averaged intermolecular interactions, is determined by the “contact” potential in the vicinity of molecules, i.e. by the shape of their van der Waals surface. To reflect the topology of the crystal field, an approximate van der Waals group Ğ of the average local field acting on a molecule and asymmetryas of the molecular surface composed of atomic van der Waals spheres, as its total misfit to Ğ, were introduced. The scheme was applied to organic compounds whose molecules have a mirror symmetry plane; the shape of two-dimensional sections of their van der Waals surfaces by this plane was analysed. Calculated values of molecular asymmetry parallel as yet uninterpreted trends in melting point data such as oscillations between “even” and “odd” n-alkanes CnH2n+2, reduced melting temperatures of monosubstituted derivatives with highly-symmetric molecular cores (e.g. toluene), and non-trivial mp orders among the isomers of disubstituted ethylenes C2H2X2 (“gem-<cis-<trans-”), substituted benzenes C6H4X2 (“meta-<ortho-<para-”), C6H3X3 (“1,2,4-<1,2,3-<1,3,5-”), C6H2X4 (“1,2,3,5-<1,2,3,4-<1,2,4,5-”), and disubstituted naphthalenes. The observed mp trends do not display any notable correlation with molecular moments of mass and charge distribution, thus being dictated mostly by van der Waals forces.

Magnetoelasticity of R 2Co 13.6Si 3.4 (R=U,Lu)

The spontaneous molecular magnetic moment M s =5.15 μ B and the Curie temperature T C =208 K of the uniaxial ferromagnet U 2Co 13.6Si 3.4 are considerably lower than that of the isostructural compound Lu 2Co 13.6Si 3.4. The magnetic and magnetoelastic properties of both compounds show no evidence of a U-sublattice contribution to the magnetism.

Mechanisms and Approximations in Macromolecular Reactions: Reversible Initiation, Chain Scission, and Hydrogen Abstraction

Understanding the evolution of distributions (e.g., molecular weight distributions of reacting macromolecules) is an important challenge in chemical reaction engineering. Mechanisms of macromolecular decomposition are typically based on free-radical processes, including initiation−termination, hydrogen abstraction, and propagation−depropagation chain-scission reactions. Common assumptions to simplify the kinetics are usually made, including the quasi-stationary-state approximation (QSSA) and the long-chain approximation (LCA). We demonstrate how integrodifferential (population balance) equations can describe such reacting systems and how molecular weight moments reveal the system dynamics. By comparing with the full numerical moment solutions, we evaluate the LCA and QSSA for zeroth, first, and second moments. A major conclusion is that LCA fundamentally changes the overall kinetics, whereas QSSA only slightly alters the initial time dependence. Ignoring the initiation reaction causes hydrogen abstraction to play a substantial role and yields an exponential time behavior for polymer moles. The full complement of reactions and the approximation with QSSA show a quadratic temporal increase in polymer moles.

Co(II), Ni(II), and Cu(II) Complexation with Isatin Aminoguanisone and Nitroaminoguanisone

New complexes of bivalent Co, Ni, and Cu with isatin aminoguanisone (HL) and nitroaminoguanisone (HL1) of the composition ([Co(HL)2]Cl2 (I), [Ni(HL)2]Cl2 (II), [Cu(L)Cl] (III), [Co(L1)2] (IV), [Ni(L1)2] (V), and [Cu(L1)2] (VI) are synthesized. Their molecular conductivities and effective magnetic moments are measured and thermal stabilities are studied. The type of the ligand coordination in I–VI is proposed on the basis of IR data. The summary of physicochemical data for I–VI and the energy calculations for their molecules by the molecular mechanics method made it possible to establish stoichiometry of the coordination polyhedra of the complexes.

Calculation of molecular electric and magnetic multipole moment integrals of integer and noninteger n Slater orbitals using overlap integrals

AbstractClosed formulas are established for the magnetic multipole moment integrals of integer and noninteger n Slater‐type orbitals (ISTOs and NISTOs) in terms of electric multipole moment integrals for which the analytic expressions through the overlap integrals with ISTOs and NISTOs are derived. The overlap integrals are evaluated by the use of auxiliary functions. Using the derived expressions the multipole moment integrals, and therefore the electric and magnetic properties of molecules, can be evaluated most efficiently and accurately. © 2003 Wiley Periodicals, Inc. Int J Quantum Chem, 2003

Structural requirements for potent anti-human immunodeficiency virus (HIV) and sperm-immobilizing activities of cyclohexenyl thiourea and urea non-nucleoside inhibitors of HIV-1 reverse transcriptase.

The current pandemic of sexually transmitted human immunodeficiency virus (HIV)/acquired immunodeficiency syndrome (AIDS) has created an urgent need for a new type of microbicide, one that is both a spermicide and a virucide. In a systematic effort to identify a non-detergent-type antiviral spermicide, we have rationally designed and synthesized a series of cyclohexenyl thiourea (CHET) nonnucleoside inhibitors (NNIs) of HIV-1 reverse transcriptase (RT) with sperm-immobilizing activity (SIA). To gain further insight into the structural requirements for the optimal activity of these dual-function NNIs, we compared the effects of thiazolyl, benzothiazolyl, and pyridyl ring substitutions and functionalization with electron-donating and electron-withdrawing groups as well as the importance of thiourea and urea moieties of 15 heterocyclic ring-substituted NNIs. RT activity and p24 antigen production in HIV-infected peripheral blood mononuclear cells were used as markers of viral replication. Computer-assisted sperm analysis was used for evaluating SIA of CHET compounds. The rabbit model was used for evaluation of in vivo mucosal toxicity and contraceptive activity of the lead NNIs. Three CHET-NNIs with a bromo, chloro, or methyl substitution at the 5 position of the pyridyl ring exhibited potent anti-HIV activity at nanomolar concentrations (IC(50) = 3-5 nM) and SIA at micromolar concentrations (EC(50) = 45-96 micro M). The dual-function CHET-NNIs were potent inhibitors of drug-resistant HIV-1 strains with genotypic and phenotypic NNI resistance. Upon substitution of the sulfur atom of the thiourea moiety with an oxygen atom, the most striking difference noted was a 38-fold reduction in time required for 50% sperm immobilization (T(1/2)). A quantitative structure-activity relationship (QSAR) analysis was used in deriving regression equations between 20 physicochemical properties and SIA of NNIs. QSAR analysis showed that the T(1/2) values positively correlated with values for molecular refractivity (r = 0.88), hydrophobicity (r = 0.72), atomic polarizability (r = 0.70), and principal moment of inertia (r = 0.63) of spermicidal NNIs. A stepwise multiple regression model to describe the relationship of T(1/2) values with these four regressors provided excellent predictability (r = 0.93). Exposure of semen to thiourea/urea NNIs either alone or in combination at the time of artificial insemination led to marked or complete inhibition of pregnancy in rabbits as assessed by the number of embryo implants versus corpora lutea on Day 8 of pregnancy. Repeated intravaginal application of a gel-microemulsion with and without 0.5%, 1%, and 2% CHET-NNI or its urea analog either alone or in combination did not induce mucosal toxicity. We hypothesize that the gain of spermicidal function by CHET-NNIs is due to their metabolic oxidation to urea analogs by sperm. Three reaction pathways are discussed. The extremely rapid SIA of the urea analog as well as the broad-spectrum anti-HIV activity of spermicidal CHET-NNIs together with their lack of mucosal toxicity and the marked ability to reduce in vivo fertility is particularly useful for the clinical development of a dual-function spermicidal microbicide. The cyclohexenyl pyridyl NNIs, especially N-[2-(1-cyclohexenyl)ethyl] N'-[2-(5-bromopyridyl)]-thiourea in combination with the urea analog, show unique clinical potential as anti-HIV spermicides aimed at curbing the sexual transmission of multidrug-resistant HIV-1 while providing effective fertility control for women.

Magnetic Anisotropy of U2(Fe1-xCox)13.6Si3.4 (0≤x≤0.5)

Single crystals of the U2(Fe1-xCox)13.6Si3.4 (x=0, 0.1, 0.2, 0.3, 0.4, 0.5) solid solutions (hexagonal crystal structure of the Th2Ni17 type) were prepared for first time and their magnetization was measured at 4.2 K along the principal axes. The alloys exhibit a large basal-plane type magnetocrystalline anisotropy. Strong non-linearity of hard-direction magnetization curves and especially first-order magnetization process (FOMP) at low x values needs for description a large second anisotropy constant K2 which cannot be provided by the Fe sublattice and is, therefore, a strong evidence for magnetic ordering of U sublattice. K2 turns from negative to positive with increasing x at x = 0.2 which is reflected in disappearance of FOMP. The molecular spontaneous magnetic moments Ms decreases from 23 to 14 μB/f.u. whereas the Curie temperatures TC increases from 530 K to 595 K with increasing x from 0 to 0.5.

Vibronic dynamic problem of the valence tautomeric interconversion [low-spin Co(III)(N∧N)(sq)(cat)] ↔ [high-spin Co(II)(N∧N)(sq)2]. Magnetic properties and charge-transfer band

For a single valence tautomeric complex the vibronic problem of pseudo-Jahn–Teller effect is solved. The vibronic (hybrid) wave-functions and energy levels are used for the calculation of the temperature dependence of the molecular magnetic moment and the shape of the optical band in the near infrared range. The magnetic moment is shown to increase gradually from 1.73μB to 4.34μB. The spectrum of the isolated complex in the near infrared range is revealed to represent a band related to the light induced transfer of an electron from the cat ligand to the metal ion. The suggested model is in qualitative agreement with the experimental data.

Molecular transition moments at large internuclear distances

The behavior of the dipole moments of molecular transitions is analyzed as a function of the internuclear distance R and it is shown that for allowed transitions the departure of the dipole moment from the value for the unperturbed atom varies as ${R}^{\ensuremath{-}3}$ with a coefficient that can be obtained from the dynamic polarizability of one atom evaluated at the unperturbed transition frequency of the other.

Calculation of Molecular Weight Distributions in Non-Linear Free-Radical Polymerization Using the Numerical Fractionation Technique

Mathematical Modeling of non-linear polymerization systems subject to gel formation is a challenging endeavor. At the gel point, the second and higher molecular weight moments diverge to infinity making it impossible to obtain the molecular weight distribution (MWD). The numerical fractionation (NF) technique utilizes a refinement of the method of moments to model non-linear polymerization systems that form gel. Since the method of moments yields results in terms of average quantities, some information is lost when reconstructing the MWD using NF. As a consequence, a broad shoulder appears at the high chain length end of the MWD tail. This study demonstrates that the validity of the gamma distribution deteriorates for the broader branched polymer generations and evaluates the performance of various alternative model distributions. Proper selection of the model distribution enhances the NF-reconstructed MWD. Illustration of closure approximations derived from known distribution functions, and proposed closure for the direct solution.

Antimicrobial, Antifertility and Antiinflammatory Approach toTetradentate Macrocyclic Complexes of Iron(II) and Manganese(II)

Some antifertility inhibitors of 18 to 24-membered tetraazamacrocyclic complexes of iron(II) and manganese(II) have been synthesised by the template condensation using 1,3-phenylenediamine with malonic acid, succinic acid, glutaric acid and adipic acid. The reaction proceed smoothly to completion. The complexes were characterized by elemental analyses, molecular weight determinations, infrared, electronic, magnetic moment, mössbaur and mass spectral studies. The elemental analyses are consistent with the formation of the complexes [M(N4Ln)Cl2] (M = Fe(lI) or Mn(II)). All these complexes are stable and monomeric in nature as indicated by the molecular weight determinations. The spectral studies confirm the octahedral geometry around the central metal atom. The complexes have been screened in vitro against a number of fungi and bacteria to assess their growth inhibiting potential. The testicular sperm density and testicular sperm morphology, sperm motility, density of cauda epididymal spermatozoa and fertility in mating trials and biochemical parameters of reproductive organs have been examined and discussed.

Structural and Antimicrobial Studies of Some Divalent Transition Metal Complexes with Some New Symmetrical Bis (7-Formylanil Substituted-Sulfoxine) Schiff Base Ligands

Symmetrical bis (7-formyanil substituted-8-hydroxyquinoline-5-sulfonic acid), Schiff bases, react with Co(II), Ni(II) and Cu(II) ions to give MnL (n=1, 2) complexes as established by conductometric titration in 1 : 1 DMF: H2O. The complexes were identified by elemental analyses, molecular weight determination, thermal analysis, infrared, magnetic moments, electronic absorption, and electron spin resonance spectra. The suggested general geometry for these complexes may have a tetrahedral crystal structure and the general formula is [M2L(OH24], where M(II) = Co, Ni and Cu and L = 7―X―H2 L(―X―= dimethyl, p-phenyl, o-phenyl), while for the, trimethyl, ligand and the tetrahedral crystal structure has the general formula [M2L(OH2)2].Antimicrobial activity of these ligands and their transition metal complexes has been investigated on some common fungi and bacteria. A considerable increase in the biocide acticity of these ligands has been observed on coordination with transition metal ions, therefore, these complexes can be used in the chemotherapy of candidiaces and other fungal skin diseases.

Structural and Microbial Studies of some Transition Metal Complexes of 7-Substituted-8-Hydroxyquinoline-5-Sulphonic Acid Ligands

The reaction of 7-substituted derivatives of the ligand 5-sulpho-8-hydroxyquinoline (7-X-HL), (X=H, NH 2 , NO 2 and I), with some biologically important transition metal ion such as {Cr(III), Fe(III), Mn(II), Fe(II), Co(II), Ni(II), and Cu(II)} was investigated. The formation of ML n (n=1, 2) complexes of the ligand Na[7-I-HL] has been established by conductometric titrations in 10% (v/v) ethanol-water. The complexes of the ligands with all of the above transition metal ions which have been synthesized were characterized by elemental analyses, molecular weight determinations, X-ray diffraction (XRD), magnetic moments (µ eff ), and thermal analyses (DTA and TG). The data suggest the composition of these complexes, which have an octahedral coordination. The general formula is Na 2 [ML 2 (H 2 O) 2 ]·4H 2 O where M(II)=Mn, Fe, Co, Ni and Cu. The thermal analyses of the complexes show that for Na 3 [ML 3 ]·6H 2 O where M(III)=Cr and Fe all water molecules are lattice water. The antibacterial activity of these ligands and their divalent transition metal complexes has been determined on gram-positive ( Sarcina lutea ) and gram-negative ( Escherichia coli ) bacteria at 37°C, and antifungal activity has been determined on common fungi viz . ( Aspergillus niger , and Candida albicans ) at 30°C. A considerable increase in the biocidal activity of these ligands on being coordinated with transition metal ions has been reported. These compounds can be recommended to use for the chemotherapy of candidiaces and other fungal skin diseases.