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The near infrared (NIR) spectra of bis(ethylene-1,2-dithiolato)nickel, Ni(C(2)S(2)H(2))(2) are fully interpreted here by applying a method developed for efficient automatic computation of both the infrared wave numbers and the intensities. The employed procedure uses parallel variational multiple window configuration interaction wave functions, the so-named P_VMWCI(2) algorithm, which incorporates both the mechanical and the electric anharmonic effects. It is shown that inclusion of anharmonicities is crucial for correctly assigning the fundamental, combination, and overtone vibrational frequencies in the infrared spectrum of the target system, for which conflicting assignments are found in literature.

Electronic and vibrational nuclear relaxation (NR) contributions to the dipole (hyper)polarizabilities of the endohedral fullerene Li@C60 and its monovalent cation [Li@C60]+ are calculated at the (U)B3LYP level. Many results are new, while others differ significantly from those reported previously using more approximate methods. The properties are compared with those of the corresponding hypothetical noninteracting systems with a valence electron transferred from Li to the cage. Whereas the NR contribution to the static linear polarizabilities is small in comparison with the corresponding electronic property, the opposite is true for the static hyperpolarizabilities. A relatively small, but non-negligible, NR contribution to the dc-Pockels effect is obtained in the infinite frequency approximation. © 2010 Wiley Periodicals, Inc. J Comput Chem, 2011

In the present study we report on the linear and nonlinear optical properties of C(60)-triphenylamine (TPhA) hybrids. The synthesized materials were prepared following the 1,3-dipolar cycloaddition of azomethine ylides onto the skeleton of C(60) forming the TPhA-based monoadduct, equatorial bis-adduct and dumbell C(60). Complementary spectroscopic techniques, such as NMR, MALDI-TOF-MS, and ATR-IR are applied for the structural characterization of the hybrid materials, while intermolecular electronic interactions are investigated by UV-Vis measurements. In all considered cases, C(60) serves as an acceptor while the triphenylamine unit is chosen as a donor. In order to investigate the dependence of the second-order hyperpolarizability on the architecture of the systems (D-A, A-D-A) we use a Z-scan technique employing 532 nm, 35 ps laser pulses. We have found that the total second-order hyperpolarizability of the C(60)-TphA-C(60) system is several times larger than that of TPhA-C(60). The results of experimental measurements are supported by quantum-chemical calculations.

When X-ray structure of a ligand-bound receptor is not available, homology models of the protein of interest can be used to obtain the ligand-binding cavities. The steroelectronic properties of these cavities are directly related to the performed molecular model coordinates. Thus, the use of different template structures for homology may result in variation of ligand-binding modes. We have recently reported the MD simulations of a potent CB ligand at bovine rhodopsin-based CB1 and CB2 receptors (Durdagi et al., Bioorg Med Chem 16:7377-7387, 2008). In this present study, a homology modeling study based on the beta2-adrenergic receptor for both CB1 and CB2 receptors was performed, and the results were compared with rhodopsin-based models. In addition, the role of membrane bilayers to the adopted conformations of potent AMG3 CB ligand has been analyzed for receptor-free and membrane-associated receptor systems. The performed MD trajectory analysis results have shown that gauche conformations at the terminal segment of the alkyl side chain of AMG3 are not favored in solution. Different adopting dihedral angles defined between aromatic and dithiolane rings at the active sites of the CB1 and CB2 receptors, which are adapted lead to different alkyl side chain orientations and thus, may give clues to the medicinal chemists to synthesize more selective CB ligands. The binding sites of receptors derived by rhodopsin-based models have been regenerated using the beta2-adrenergic based template receptors. The re-obtained models confirmed the ligand-binding pockets that were derived based on rhodopsin.

A database has been derived from recently reported [60]fullerene derivatives, and their binding scores with HIV-1 PR have been computed using docking techniques. Computational methods have been used to predict which derivatives may have high binding affinities, and for these compounds biological tests have been performed with purified PR. Experimental results confirm the high binding scores of fullerene derivatives predicted from the docking calculations. Our measurements showed that the fullerene derivative (Fmoc-Baa) has about three times better inhibitory binding (Ki ) 36 nM) than the most active fullerene-based inhibitor (Ki ) 103 nM) currently available.

Nucleic acids and proteins are biochemically important complexes responsible for heirdom and miscellaneous enzymatic cellular processes. Thus, the understanding of the physical origins of their stability, i.e., the nature of intermolecular interactions, is crucial for the interpretation of various biochemical processes. The intercalation of drugs into DNA may serve as an illuminating example. The most accurate and reliable framework for the analysis of intermolecular interactions is provided by the quantum mechanics. In general, two distinct approaches are usually used for the evaluation of interaction energies, namely the supermolecular approach and the perturbation theory. While the former explains the interaction energy as small difference between the values of the energy of the whole complex and the sum of energies of the monomers, the latter allows for direct calculation of contributions with a clear physical interpretation. Unfortunately, the majority of studies of the nucleic acid base complexes had either shown little concern for the elucidation of the nature of interactions or analyzed this aspect qualitatively. The present contribution is especially aimed at the compact and comprehensible presentation of the most important observations made on the physical origins of nucleic acid base pairs’ stability. Throughout, we shall support the discussion by our own findings in this fascinating area.

For the first time, a set of renin inhibitors were subjected to the 3D QSAR/CoMFA and CoMSIA studies. The utility of renin inhibitors in the treatment of cardiovascular diseases has not been fully explored yet. At the moment, aliskiren is the first and only existing renin inhibitor in the drug market. The performed 3D QSAR/CoMFA and CoMSIA in combination with docking studies included aliskiren and 37 derivatives possessing a wide variety of bioactivity. The obtained results may aid in the design of novel bioactive renin inhibitors.

Some linear and nonlinear optical (NLO) properties of Ni(SCH)4 and several of its derivatives have been computed by employing a series of basis sets and a hierarchy of methods (e.g., HF, DFT, coupled cluster, and multiconfigurational techniques). The electronic structure of Ni(SCH)4 has been also analyzed by using CASSCF/CASPT2, ab initio valence bond, and DFT methods. In particular we discuss how the diradicaloid character (DC) of Ni(SCH)4 significantly affects its NLO properties. The quasidegeneracy of the two lowest-energy singlet states 1 mathg and 1 math1u, the clear DC nature of the former, and the very large number of low-lying states enhance the NLO properties values. These particular features are used to interpret the NLO properties of Ni(SCH)4. The DC of the considered derivatives has been estimated and correlated with the NLO properties. CASVB computations have shown that the structures with Ni(II) are the dominant ones, while those with Ni(0) and Ni(IV) have negligible weight. The weights of the four diradical structures were discussed in connection with the weight of the structures, where all the electrons are paired. Comparative discussion of the properties of Ni(SCH)4 with those of tetrathia fulvalene demonstrates the very large effect of Ni on the properties of the Ni-dithiolene derivatives. A similar remarkable effect on the NLO properties is produced by one or two methyl or C3S groups. The considered Ni-dithiolene derivatives have exceptionally large NLO properties. This feature in connection with their other physical properties makes them ideal candidates for photonic applications. Luis.Serrano@uv.es

Using a wide variety of quantum-chemical methods we have analyzed in detail the linear and non-linear optical properties of [60]fullerene-chromophore dyads of different electron-donor character. The dyads are composed of [60]fullerene covalently linked with 2,1,3-benzothiadiazole and carbazole derivatives. Linear scaling calculations of molecular (hyper)polarizabilities were performed using wave function theory as well as density functional theory (DFT). Within the former approach, we used both semiempirical (PM3) and ab initio (Hartree-Fock and second-order Møller-Plesset perturbation theory) methods. Within the latter approach only the recently proposed long-range (LRC) schemes successfully avoid a large overshoot in the value obtained for the first hyperpolarizability (β). Calculations on model fullerene derivatives establish a connection between this overshoot and the electron-donating capability of the substituent. Substitution of 2,1,3-benzothiadiazole by the triphenylamine group significantly increases the electronic first and second hyperpolarizabilities as well as the two-photon absorption cross section. For [60]fullerene-chromophore dyads we have, additionally, observed that the double harmonic vibrational contribution to the static beta is much larger than its electronic counterpart. The same is true for the dc-Pockels β as compared to the static electronic value, although the vibrational term is reduced in magnitude; for the intensity-dependent refractive index the vibrational and electronic terms are comparable. A nuclear relaxation treatment of vibrational anharmonicity for a model fulleropyrrolidine molecule yields a first-order contribution that is substantially more important than the double harmonic term for the static β.

A discrete model based on the multipolar expansion including terms up to hexadecapoles was employed to describe the electrostatic interactions in liquid acetonitrile. Liquid structures obtained form molecular dynamics simulations with different classical, nonpolarizable potentials were used to analyze the electrostatic interactions. The computed average local field was employed for the determination of the environmental effects on the linear and nonlinear electrical molecular properties. Dipole-dipole interactions yield the dominant contribution to the local field, whereas higher multipolar contributions are small but not negligible. Using the effective in-phase properties, macroscopic linear and nonlinear susceptibilities of the liquid were computed. Depending on the partial charges describing the Coulomb interactions of the force field employed, either the linear properties (refractive index and dielectric constant) were reproduced in good agreement with experiment or the nonlinear properties [third-harmonic generation (THG) and electric field induced second-harmonic (EFISH) generation] and the bulk density but never both sets of properties together. It is concluded that the partial charges of the force fields investigated are not suitable for reliable dielectric properties. New methods are probably necessary for the determination of partial charges, which should take into account the collective and long-range nature of electrostatic interactions more precisely.

A set of 30 novel Delta8-tetrahydrocannabinol and cannabidiol analogues were subjected to three-dimensional quantitative structure-activity relationship studies using the comparative molecular field analysis (CoMFA) and comparative molecular similarity indices analysis (CoMSIA) approaches. Using a combination of molecular modeling techniques and NMR spectroscopy, the putative bioactive conformation of the most potent cannabinoid (CB) ligand in the training set was determined. This conformer was used as the template and CB1 and CB2 pharmacophore models were developed. These models were fitted with experimental binding data and gave high correlation coefficients. Contour maps of the CB1 and CB2 models of CoMFA and CoMSIA approaches show that steric effects dominantly determine the binding affinities. The CoMFA and CoMSIA analyses based on the binding affinity data of CB ligands at the CB1 and CB2 receptors allowed us to deduce the possible optimal binding positions. This information can be used for the design of new CB analogues with enhanced activity and other tailored properties.

This is the first part of a study of the local field effects on (non)linear optical susceptibilities of solutions of para-nitroaniline (pNA) in three different solvents, cyclohexane (CH), 1,4-dioxane (DI), and tetrahydrofuran (THF), using a discrete molecular representation of the condensed phase. To account for dipolar and quadrupolar effects, the latter of which are especially important for DI solution, all the electric properties necessary to compute the local fields and local field gradients in quadrupolar approximation as well as the dipolar hyperpolarizabilities for the four molecules are computed, including frequency dispersion and vibrational contributions to the dipolar properties. The convergence of the perturbation treatment for the pure vibrational (PV) contributions is examined by comparison of the values obtained at the lowest order with those of partially computed second order in mechanical and electrical anharmonicity. For pNA, for which previous computations of the hyperpolarizabilities have generally found poor agreement with experimental results, a thorough investigation of the effects of solvent-induced geometry changes, dynamic and static correlation, frequency dispersion, and classical thermal averaging over the torsional modes of the substituent groups and the inversion mode of the amino group on the dipolar properties is carried out. Computations using self-consistent continuum reaction field models show that the amino group is substantially less pyramidalized in polar solvents than in the gas phase. With all the effects taken into account, reasonable agreement with the experimental electric-field induced second harmonic generation (EFISH) result on pNA vapor of Kaatz, Donley, and Shelton is obtained.

A comprehensive study of the linear and nonlinear molecular optical properties of HRgC(4)H, where Rg = Ar,Kr,Xe, has been performed. Dynamical electron correlation effects were computed by employing the coupled cluster methodology. A large electron correlation contribution to the nonlinear properties of HArC(4)H has been revealed. This contribution decreases by increasing the atomic number of the inserted rare gas atom. In order to interpret the origin of this noteworthy property, the complete active space self-consistent field method was employed. We have performed a systematic study of the linear and nonlinear electric properties by modifying the active space. The calculations have shown the significant contribution of the doubly excited sigma(*2) configuration and a negligible contribution of pi(*2). A quite remarkable discrepancy between numerically and analytically evaluated hyperpolarizabilities has also been observed for HArC(4)H. This was attributed to the contribution of near degenerate states.

The electric field poling process of free-standing films of poly(methyl methacrylate) (PMMA) matrix doped with the nonlinear optical compound 4-(dimethylamino)-4'-nitrostilbene (DMANS) was investigated by molecular simulation methods. The influence of the vacuum/bulk interfacial regions on static and dynamic properties, including the glass transition temperature Tg and the field-induced chromophore reorientation, was studied by employing films of three different thicknesses and by comparison with previous work on the bulk system. The interfacial region, defined as the region, where the local density increases from zero to the bulk density, is about 2 nm wide, independent of the film thickness. Tg decreases with decreasing film thickness, in accord with previous experimental work and theoretical predictions. The resistance against field-induced chromophore reorientation in the liquid state is found to increase strongly with the film thickness.

Several models of the confinement of the auride ion are discussed in the context of the colour of the tetramethylammonium auride crystals. These models correspond to either neutral or charged nearest neighbourhood of the auride ion as represented by a cluster of helium and He-like atoms, respectively. The models involving neutral helium clusters account for what is referred to as the confinement effect and simulate the Pauli repulsion between the auride ion and its surrounding. The charged clusters supply additional attractive potential which is shown to be indispensable for the interpretation of the large blue shift of the first absorption band of the auride ion. It is also found that the Pauli repulsion and the effect of the increase of the attractive potential due to the charged neighbourhood of the auride ion are not additive. The confinement models discussed in this paper are used to calculate the energy of the first electronic transition in the confined ion. The calculations have been carried out in the TDHF (RPA) and CASSCF/CASPT2 approximations with relativistic effects accounted for by using the Douglas-Kroll approximation. The charged confinement models are found to increase the importance of both the electron correlation and relativistic contributions to the energy of the first electronic transition in the encapsulated auride ion. The computed data are used to discuss the observed spectral transparency of the tetramethylammonium auride crystals.

The equilibrium geometry, energy, dipole polarizability, and second hyperpolarizability of the rhombic B4 -cluster with D2h symmetry are calculated by restricted (RHF) and unrestricted (UHF) Hartree-Fock theory; Moller-Plesset perturbation theory (MPn); coupled-cluster theory with singles, doubles, and a perturbational treatment for connected triples [CCSD(T)]; Brueckner doubles with a perturbational treatment for connected triples [BD(T)]; and complete active space SCF (CASSCF) and restricted active space SCF (RASSCF) methods, using three different basis sets. The multireference methods show that excited state configurations contribute appreciably to the ground state wave function. Accordingly, the RHF method yields results that differ greatly from those of the correlated methods, even for the geometry. UHF gives more reliable geometries, but suffers from high spin contamination. The electric properties calculated at reasonably highly correlated levels are qualitatively comparable for both the single reference and multireference descriptions, although differences between CCSD(T) and BD(T) are larger than usually reported in the literature and properties calculated at the MPn (n=2, 3, 4) series show much damped oscillatory behavior, especially for the components along the long in-plane axis. It is found that inclusion of f-functions in the basis set do not have a large effect on the electric properties. ©1999 John Wiley & Sons, Inc. J Comput Chem 20: 679-687, 1999.

The refractive indices (linear response) and the nonlinear susceptibility for third harmonic generation (THG) at λ=1064 nm of liquid water and benzene are predicted, using ab initio molecular (hyper)polarizabilities and local-field corrections calculated according to the Lorentz model, the generalized reaction-field model of Onsager, and a discrete local-field theory applied to liquid structures obtained by classical molecular simulation methods. The ratio of the calculated THG susceptibilities for the two liquids is compared with experimental results, in order to avoid ambiguities concerning the factors used to calibrate the THG experiments. All models are able to reproduce the experimental refractive indices of both liquids accurately, but are less successful for the THG susceptibility. The discrete local-field corrections for the THG susceptibility are considerably larger than those of the continuum model in the form of the more accurate extended reaction-field approach.

The dipole moments μ, polarizabilities α, and first and second hyperpolarizabilities, β and γ of LiH, NaH and KH (MeH) have been computed using Hartree-Fock, MP2 and CCSD(T) theories. The static electronic and vibrational contributions to these properties are presented. The vibrational properties have been analysed into contributions due to zero-point vibrational averaging and pure vibrational terms. An alternative dissection of the vibrational properties into nuclear relaxation and curvature terms has also been considered. KH has been selected as a model system to study how the number of electrons, which are correlated (2, 10 and 20) affect both electronic and vibrational properties. The 10 electron approximation gives results that are practically the same as those computed by taking into account all 20 electrons of KH. The double-harmonic approximation has been shown to give satisfactory results for the pure vibrational contributions to the polarizability and the first hyperpolarizability, while this ap...

The first hyperpolarizabilities β of a redox pair of molecules, containing an octamethylferrocene donor linked by an ethenyl chain to a nitrothiophene acceptor, calculated at the SCF level, predict a much larger β value for the cation than for the reduced form, which is in contradiction to previous experimental findings. It is shown that the ground state of the oxidised form cannot be described by a single reference configuration. A multi-configurational description of the cation leads to a much smaller value for the dominant component of β, bringing the relative computed values in qualitative agreement with experiment.

Molecular dynamics (MD) simulation and subsequent analysis of the macroscopic polarization developed in response to “a posteriori” applied electric fields or of spontaneous fluctuations in the instantaneous polarization under zero applied field is used to assess the nonlinear optical properties of a polarizable liquid. Three strategies are proposed for the electrostatic analysis, all using as input static “gas phase” (hyper)polarizabilities, obtained from ab initio calculations. All three strategies are shown to accurately reproduce the experimentally measured refractive index and second nonlinear susceptibility of liquid benzene. The simulation also predicts the distribution of orientations and magnitudes of the local electric fields experienced by the molecules in the liquid, and the nonlinear contributions to the local fields. This approach gives an 8% higher estimate of the second nonlinear susceptibility of liquid benzene than the Lorentz local field factor approach, in better agreement with experimental values.

The second-order polarizability components βzzz, βzyy and βyzy=βyyz of N,N′-dihexyl-1,3-diamino-4,6-dinitrobenzene (DHADNB) have been determined by combination of polarization dependent electric-field-induced second-harmonic generation (EFISHG) and hyper-Rayleigh scattering (HRS) experiments in dioxane solution at T=298 K. Dipole moments of the first three optically allowed excited singlet-states were obtained from electrooptical absorption measurements (EOAM) in methylcyclohexane solution. The results show that the second-order polarizability of this two-dimensional (2D) non-linear optical (NLO) chromophor is completely dominated by the off-diagonal components βzyy and βyzy=βyyz, whereas the contribution of βzzz is nearly insignificant. Independent quantum chemical calculations confirm these findings. Although DHADNB is a dipolar molecule, non-dipolar three-level contributions to β are found to be much larger than dipolar two-level contributions.

The polarizabilities and hyperpolarizabilities of C8H6, C8H6Li2 and C8H6Na2 have been computed using MP2 theory. Optimized structures have been employed. The effect of changes in the geometry on the properties is discussed. Distortions induced by lithium and sodium in the anionic moieties are documented. Evidence for the electronic instability of pentalenyl dianion is presented. It has been found that introduction of lithium and sodium into the molecular structure leads to derivatives with very large hyperpolarizabilities. It is thus proposed that organolithium and organosodium compounds are very likely to lead to materials with the required very large nonlinearities, which are necessary in many scientific and industrial applications. Molecular Physics

Static and dynamic polarizabilities and second hyperpolarizabilities are presented for ethylene, including electronic, pure vibrational and zero-point vibrational averaging (ZPVA) contributions. Static pure vibrational hyperpolarizabilities are of commensurate size with their electronic counterparts but show less dependence on basis set and (MP2) electron correlation. A Hartree–Fock estimate for the static ZPVA correction to γ is found to be 10% of the corresponding electronic contribution. The dynamic pure vibrational hyperpolarizability, despite being significant for the optical Kerr effect and intensity-dependent refractive index, reduces in magnitude for second and third harmonic generation, leaving ZPVA as the dominant vibrational effect.

The 3-aminoacroleine molecule is used as a model to study the dependence of linear and nonlinear molecular electric properties on the molecular conformation. Among four conformers of this molecule one of them has the intramolecular hydrogen bond, and thus, permits the study of its effect on electric properties. It has been established on the basis of MP2 calculations that the most elongated conformer of 3-aminoacroleine has the largest values of the dipole moment, dipole polarizability, and first hyperpolarizability. They were found to significantly depend on the conformation of the molecule. Also the electron correlation effect on the first hyperpolarizability is found to be very large. The results calculated for four conformers permit also to estimate the effect of the intramolecular hydrogen bond. The incremental lowering of the dipole polarizability is negligible whereas that for the first hyperpolarizability is of the order of −120 a.u. Considerable attention has been paid to the calculation of vibration corrections to electric properties. For the dipole polarizability and first hyperpolarizability the so-called pure vibrational corrections are found to be unusually large. These large values arise from the use of the harmonic zeroth-order approximation in the perturbation treatment of contributions due low-frequency modes. It is concluded that the perturbation method for the evaluation of pure vibrational corrections to electric properties should be used with great care and possibly preceded by the analysis of low frequency modes.

The polarizability (α) and the second hyperpolarizability (γ) of tetrakis(phenylethynyl)ethene (TPEE) are compared and analyzed in connection with the properties (α, γ) of a series of selected/designed molecules having different conjugation patterns. Several lithiated derivatives of TPEE are designed and shown to have very enhanced second hyperpolarizabilities; for example, one of the lithiated TPEE has a 1.6×103 times larger second hyperpolarizability than that of benzene. The potential of the proposed derivatives for applications in photonics is noted. The polarizabilities and the hyperpolarizabilities of the considered molecules have been computed employing the PM3 method which has been proven to be adequate for the present comparative study. ©1999 John Wiley & Sons, Inc. Int J Quant Chem 72: 177–187, 1999

Dipole moments, linear and non-linear polarizabilities of [Mo(NO){HB(dmpz)3}Cl{OC6H4[CHCHC6H4N(CH3)2-4]-4} (dmpz = 3,5-dimethylpyrazolyl) (DMAMoS) and p,p′-dimethylaminonitrostilbene (DMANS) calculated at the SCF and second-order Moller–Plesset correlation (MP2) level with an effective core potential (ECP) basis set are reported. It is shown for DMANS that the ECPs are as accurate as calculations using all-electron basis sets of comparable quality. The effect of diffuse functions on the dominant components of the hyperpolarizabilities of DMANS is small. The dipole moment and linear polarisabilities of DMANS are in very good agreement with experimental values. The calculated hyperpolarisabilities are much smaller than the reported experimental values, but there are large uncertainties among the latter concerning calibration factors, concentration dependence and permanent local field effects, which render direct comparison difficult. Electronic correlation effects on the hyperpolarisabilities are large, especially for DMAMoS, for which the dominant component of the first hyperpolarisability increases by a factor of 5. Generally, the hyperpolarisabilities of DMANS are found to be larger than those of DMAMoS, in spite of the highly polarisable electronic charge-transfer character of the latter.

For the first time, a set of experimentally reported [60] fullerene derivatives were subjected to the 3D-QSAR/CoMFA and CoMSIA studies. The aim of this study is to propose a series of novel [60] fullerene-based inhibitors with optimal binding affinity for the HIV-1 PR enzyme. The position of the template molecule at the cavity of HIV-1 PR was optimized and 3D QSAR models were developed. Relative contributions of steric/electrostatic fields of the 3D-QSAR/CoMFA and CoMSIA models have shown that steric effects govern the bioactivity of the compounds, but electrostatic interactions play also an important role.The de novo drug design Leapfrog simulations provided a series of novel compounds with predicted improved inhibition effect.

A series of experimentally reported as well as computationally designed monoadducts and bisadducts of [60]fullerene analogues have been used in order to analyze the binding interactions between fullerene based inhibitors and HIV-1 PR employing docking studies. MD simulations of ligand-free and the inhibitor bound HIV-1 PR systems complemented the above studies and provided proper input structure of HIV-1 PR in docking simulations. The obtained results revealed a different orientation of the b-hairpin flaps at these two systems. In inhibitor bound system, the flaps of the enzyme are pulled in toward the bottom of the active site (the closed form) while, in ligand-free system flaps shifted away from the dual Asp25 catalytic site and this system adopts a semi-open form. The structural analysis of these systems at catalytic and flexible flap regions of the HIV-1 PR through the simulation, assisted in understanding the structural preferences of these regions, as well as, the adopted orientations of fullerene derivatives within the active site of the enzyme. Five different combinations of steroelectronic fields of 3D QSAR/CoMSIA models were obtained from the set of biologically evaluated and computationally designed fullerene derivatives (training set = 43, test set = 6) in order to predict novel compounds with improved inhibition effect. The best 3D QSAR/CoMSIA model yielded a cross validated r 2 value of 0.739 and a non-cross validated r 2 value of 0.993. The derived model indicated the importance of steric (42.6%), electrostatic (12.7%), H-bond donor (16.7%) and H-bond acceptor (28.0%) contributions. The derived contour plots together with de novo drug design were then used as pilot models for proposing the novel analogues with enhanced binding affinities. Such structures may trigger the interest of medicinal chemists for novel HIV-1 PR inhibitors possessing higher bioactivity

The combination of NMR spectroscopy and molecular modeling studies provided the putative bioactive conformation for the analgesic cannabinoid (CB) ligand (−)-2-(6a,7,10,10a-tetrahydro-6,6,9-trimethylhydroxy-6 H -dibenzo[ b , d ]pyranyl)-2-hexyl 1,3-dithiolane which served as a template in reported three-dimensional quantitative structure–activity relationship (3D QSAR) studies [Durdagi et al., J. Med. Chem. 2007 , 50 , 2875]. The reported 3D models of the CB1 receptor allowed us to construct a new 3D QSAR model based on theoretical calculations and molecular docking studies. Statistical comparison of the constructed two 3D QSAR studies showed the improvement of the new model. In addition, the new model can explain more effectively the experimental data and thus it can serve more efficiently in the rational drug design of pharmacologically optimized CB analogues.

A series of novel [60]fullerene-ferrocene and [60]fullerene-porphyrin dyads, in which a fullerene and an electron donating moiety are attached through a flexible triethylene glycol linker are synthesized and their nonlinear optical (NLO) response studied. Specifically the third-order susceptibility chi((3)) of all fullerene derivatives are measured in toluene solutions by the optical Kerr effect (OKE) technique using 532 nm, 35 ps laser pulses and their second hyperpolarizability gamma are determined. All fullerene dyads studied exhibit enhancement of their NLO response compared to pristine fullerenes which has been attributed to the formation of a charge separated state. All experimentally measured hyperpolarizability gamma values are also calculated by the semiempirical methods AM1 and PM3. A good correlation is found between the theoretical and experimental values, suggesting that simple semi-empirical methods can be employed for the designing and optimization of the fullerene-containing dyads displaying improved nonlinear responses.

The linear and nonlinear optical properties (L&NLO) of HArF, HXeOH and HXeSH are reported. The very significant effect, which the inserted noble gas atoms, has on the properties of the resulting derivative, is discussed and interpreted. The property values have been computed by employing a systematically built series of basis sets, aug‐cc‐pVnZ, and a hierarchy of computational techniques (HF, MP2, CCS, CCSD(T)). Electronic and vibrational contributions to L&NLO properties are presented. We have also discussed the effect of the local field (LF) on the L&NLO properties of HXeOH and HXeSH. The LF is created by the surrounding Xe atoms, since the molecules of interest are synthesized in a Xe matrix. It has been found that the effect of LF on some L&NLO properties is remarkable.

We employ a series of state-of-the-art computational techniques to study the effect of inserting one or more Xe atoms in HC2H and HC4H, on the linear and nonlinear optical (L&NLO) properties of the resulting compounds. It has been found that the inserted Xe has a great effect on the L&NLO properties of the organoxenon derivatives. We analyze the bonding in HXeC2H, and the change of the electronic structure, which is induced by inserting Xe, in order to rationalize the observed extraordinary L&NLO properties. The derivatives, which are of interest in this work, have been synthesized in a Xe matrix. Thus the effect of the local field (LF), due to the Xe environment, on the properties of HXeC2H, has also been computed. It has been found that the LF effect on some properties is significant. The calculations have been performed by employing a hierarchy of basis sets and the techniques MP2 and CCSD(T) for taking into account correlation. For the interpretation of the results we have employed the complete active space valence bond and CASSCF/CASPT2 methods. Luis.Serrano@uv.es

Geometries, inversion barriers, static and dynamic electronic and vibrational dipole polarizability (alpha), and first (beta) and second (gamma) hyperpolarizability of the pyrrole homologues C(4)H(4)XH (X = N, P, As, Sb, Bi) have been calculated by Hartree-Fock, Møller-Plesset second-order perturbation theory, coupled-cluster theory accounting for singles, doubles, and noniterative triple excitations methods, as well as density functional theory using B3LYP and PBE1PBE functionals and Sadlej's Pol and 6-311G basis sets. Relativistic effects on the heavier homologues stibole and bismole have been taken into account within effective core potential approximation. The results show that the electronic (hyper)polarizabilities monotonically increase with the atomic number of the heteroatom, consistent with the decrease in the molecular hardness. Ring planarization reduces the carbon-carbon bond length alternation of the cis-butadienic unit, enhancing the electronic polarizability values (alpha(e)) by 4-12% and the (hyper)polarizability values (and gamma(e)) by 30-90%. Pure vibrational and zero-point vibrational average contributions to the (hyper)polarizabilities have been determined within the clamped nucleus approach. In the static limit, the pure vibrational hyperpolarizabilities have a major contribution. Anharmonic corrections dominate the pure vibrational hyperpolarizabilities of pyrrole, while they are less important for the heavier homologues. Static and dynamic electronic response properties of the pyrrole homologues are comparable to or larger than the corresponding properties of the furan and cyclopentadiene homologue series.

The goal of this study was to develop a series of allopregnanolone analogues substituted by conformationally constrained 17beta side chains to obtain additional information about the structure-activity relationship of 5alpha-reduced steroids to modulate GABA(A) receptors. Specifically, we introduced alkynyl-substituted 17beta side chains in which the triple bond is either directly attached to the 17beta-position or to the 21-position of the steroid skeleton. Furthermore, we investigated the effects of C22 and C20 modification. The in vitro binding affinity for the GABA(A) receptor of the new analogues was measured by allosteric displacement of the specific binding of [(3)H]4'-ethynyl-4-n-propyl-bicycloorthobenzoate (EBOB) to GABA(A) receptors on synaptosomal membranes of rat cerebellum. An allosteric binding model that has been successfully applied to ionotropic glycine receptors was employed. The most active derivative is (20R)-17beta-(1-hydroxy-2,3-butadienyl)-5alpha-androstane-3-ol (20), which possesses low nanomolar potency to modulate cerebellar GABA(A) receptors and is 71 times more active than the control compound allopregnanolone. Theoretical conformational analysis was employed in an attempt to correlate the in vitro results with the active conformations of the most potent of the new analogues.

The polarizability and first and second hyperpolarizabilities of several 4,4'-disubstituted trans- stilbene (tSB) derivatives, which include the NO2 group as an acceptor (A) and several lithium containing donors (D) have been computed. Ab initio theory using a 6-31G basis set at the SCF and MP2 levels has been sued to optimize the structure of tSB and the disubstituted derivative which includes the NO2 (A) and the NLi2 (D). Their polarizabilities and hyperpolarizabilities have also been computed at the SCF level. MP2 theory has been used to assess the effect of correlation on the largest polarizability and second hyperpolarizability components of the above compounds. The preset results, together with our recent work show that the second hyperpolarizabilities of some lithiated derivatives depend quite a lot on the molecular geometries and lithiation leads to a big increase of the hyperpolarizabilities of the resulting derivatives. This finding suggests that at lest some of the lithiated derivatives are very likely to be useful for non-linear optical applications.© (1999) COPYRIGHT SPIE--The International Society for Optical Engineering. Downloading of the abstract is permitted for personal use only.

In this study we report on the electronic and vibrational (hyper)polarizabilities of donor–acceptorsubstituted azobenzene. It is observed that both electronic and vibrational contributions to the electric dipole first hyperpolarizability of investigated photoactive molecule substantially depend on the conformation. The contributions to the nuclear relaxation first hyperpolarizability are found to be quite important in the case of two considered isomers (cis and trans). Although the double-harmonic term is found to be the largest in terms of magnitude, it is shown that the total value of the nuclear relaxation contribution to vibrational first hyperpolarizability is a result of subtle interplay of higher-order contributions. As a part of the study, we also assess the performance of long-range-corrected density functional theory in determining vibrational contributions to electric dipole (hyper)polarizabilities. In most cases, the applied long-range-corrected exchange correlation potentials amend the drawbacks of their conventional counterparts

The uncertainty over the symmetry of the ground state of NiH2 is resolved, showing that it is a bent 1A1. The computations have been performed using a complete active space self-consistent field wave function (CASSCF), a second order perturbation method (CASPT2), and quasirelativistic corrections to the energy and geometry.

N-Urethane-protected γ-amino-α-cyano-β-hydroxybutenoates were synthesized as potential statine analogues and the stability of their possible tautomers was assessed using NMR, X-ray crystallography and ab initio calculations. The results establish that the cis-enol tautomeric form is the most stable one both in solution (CDCl3) and in the solid phase. In full agreement with the experimental data, the theoretical calculations predicted that the cis-enol tautomer would be the minimum energy tautomer.

The dipole moment, parallel dipole polarizability, and the parallel first hyperpolarizability of the coinage metal hydrides (CuH, AgH, AuH) are studied in the context of their vibrational contributions. The partition of the property values into pure electronic, vibrational averaging, and pure vibrational terms is discussed, and the corresponding contributions are calculated by means of the field-dependent Numerov–Cooley integration technique. The potential energy and property surfaces, required for the evaluation of these contributions, follow from different high-level electronic structure calculations. Parallel to the nonrelativistic studies, a relativistic treatment of the investigated properties has been carried out. It has been found that relativistic effects significantly reduce the magnitude of the vibrational corrections to the studied properties. A particularly large relativistic reduction has been found for the vibrational contribution to the first hyperpolarizability. The relativistic effect is enhanced with increasing nuclear charge of the heavy atom, and can be interpreted in terms of the relativistic effect on the potential energy and electric property curves.

Vibrational contributions to the dipole polarizabilities and hyperpolarizabilities of cyclopropenone and cyclopropenethione are reported. Simultaneous calculations have been carried out for the respective saturated and noncyclic counterparts of these molecules. The results have been analyzed and interpreted in terms of different structural and electronic features of the studied molecules: i.e., the oxygen–sulfur replacement, the saturation of the carbon ring, and the removal of the intramolecular strain. For static dipole polarizabilities the vibrational contribution computed at the molecular equilibrium geometry can account for more than 10% of the total value for a given component of the tensor. Both the zero-point vibrational average and pure vibrational terms are important for most of the studied molecules. In the case of the first dipole hyperpolarizability the total vibrational correction is dominated by the pure vibrational term. The vibrational corrections to dipole polarizabilities show certain regularities which can be interpreted in terms of the electronic structure of the investigated molecules. Much less clear is the pattern of behavior for the first dipole hyperpolarizability. It has been found, however, that the analysis of these data is greatly facilitated by the separate consideration of the nuclear relaxation and curvature terms. Limited study of the frequency dependence of the calculated vibrational corrections shows that in the case of the dipole polarizability, they are almost quenched to zero. In contrast, at nonzero frequencies, the vibrational contribution to the first dipole hyperpolarizability tensor β(−ω;ω,0), which determines the so-called electro-optic Pockels effect, can be as important as the pure electronic term.

Starting from a set of high-level ab initio frequency-dependent molecular first- and third-order polarizabilities, the macroscopic first-order (linear) and third-order (cubic) susceptibilities of the benzene crystal are calculated. Environmental effects are taken into account using a rigorous local-field theory and are compared with the anisotropic Lorentz field factor approach. The experimentally determined first-order susceptibility of crystalline benzene is accurately reproduced. Dispersion curves for the first-order susceptibility and results for electric-field-induced second-harmonic generation and third-harmonic generation experiments are predicted. Comparison with similar calculations conducted in the course of molecular simulations of liquid benzene shows that the theoretical results for the two phases are of comparable accuracy. Overall, the results show that for the fairly compact nonpolar benzene molecules, environmental effects on the effective molecular response are small.

The polarisability, the first and second hyperpolarisabilities of NH2—C6H4—CnHn—CHC5H4, where n= 2, 4 and 6, as well as of some related compounds are reported. The effects of isomerism, conjugation and charge-transfer on the properties are discussed. In addition the influence of increasing the length of the conjugation path on the linear and non-linear electric properties has been commented upon. The properties have been computed using an extended-basis CNDO wavefunction and the coupled Hartree–Fock perturbation theory of McWeeney et al. The employed basis sets have been shown to give polarisability (α) and second hyperpolarisability (γ) values, for some fragments of the considered molecules, in reasonable agreement with the experimental results.