QTAIM Calculations Research Articles

An integrative study to identify novel scaffolds for sphingosine kinase 1 inhibitors

Sphingosine kinase 1 (SphK1), the enzyme that produces the bioactive sphingolipid metabolite, sphingosine-1-phosphate, is a promising new molecular target for therapeutic intervention in cancer and inflammatory diseases. In view of its importance, the main objective of this work was to find new and more potent inhibitors for this enzyme possessing different structural scaffolds than those of the known inhibitors. Our theoretical and experimental study has allowed us to identify two new structural scaffolds (three new compounds), which could be used as starting structures for the design and then the development of new inhibitors of SphK1. Our study was carried out in different steps: virtual screening, synthesis, bioassays and molecular modelling. From our results, we propose a new dihydrobenzo[b]pyrimido[5,4-f]azepine and two alkyl{3-/4-[1-hydroxy-2-(4-arylpiperazin-1-yl)ethyl]phenyl}carbamates as initial structures for the development of new inhibitors. In addition, our molecular modelling study using QTAIM calculations, allowed us to describe in detail the molecular interactions that stabilize the different Ligand-Receptor complexes. Such analyses indicate that the cationic head of the different compounds must be refined in order to obtain an increase in the binding affinity of these ligands.

Theoretical insights into the nature of PtSn bond: Reevaluating the bonding/back-bonding properties of trichlorostannate with comparison to the cyano ligand.

The coordinating properties of the trichlorostannate ligand in hydrido platinum trichlorostannato and platinum bis-trichlorostannato complexes, containing various phosphine ligands, have been elucidated by means of charge decomposition analysis, the Ziegler-Rauk Energy Decomposition with the Natural Orbitals for Chemical Valence, Domain-Averaged Fermi Hole, and natural bond orbital methods. Trichlorostannate has been found to be a strong σ-donor and a weak π-acceptor ligand with coordination properties not far from those of the cyano ligand. For back-bonding, the tin-chlorine σ∗ orbitals are mostly responsible. In contrast to previous assumptions, the 5d orbitals of tin play no role at all in the interaction with the platinum center. QTAIM calculations suggest, that the platinum-tin interaction should be interpreted as donor-acceptor, rather than covalent type. Trichlorostannate has been found to have weaker trans influence in comparison to the cyano ligand. © 2017 Wiley Periodicals, Inc.

Theoretical investigation on the performance of simple and doped graphenes for the surface adsorption of various ions and water desalination

In this work, the abilities of simple and heteroatom-doped graphenes for the adsorption of several ions (sodium, calcium, magnesium, chloride, carbonate, sulfate, and nitrate) were studied using theoretical methods. The results of this work could be helpful for future studies in the water desalination projects because the considered ions are the major existing ions in water. The structures of all graphenes and their complexes with these ions were optimized in the gas phase and water (using PCM model). Moreover, the interaction energies in the gas phase and water, atomic charges, second-order perturbation energies (from NBO calculations), and QTAIM results were obtained to provide more evidences related to these interactions. The obtained energies showed more favorable interactions in water versus than those in the gas phase. Among all graphenes, aluminum-doped graphene showed the highest and nitrogen-doped graphene showed the least adsorption energies. QTAIM calculations indicated the noticeable electron densities in bond critical points for all interactions, and the Laplacians of electron densities confirmed nonbonding nature for the most of interactions. Population analyses revealed that the HOMO-LUMO gap in doped graphene was increased in comparing with simple graphene that make them as potential candidates for detection of these ions.

The interaction strengths and spectroscopy parameters of the C2H2∙∙∙HX and HCN∙∙∙HX complexes (X = F, Cl, CN, and CCH) and related ternary systems valued by fluxes of charge densities: QTAIM, CCFO, and NBO calculations.

This theoretical work exhibits a new systematic study of structural parameters, electronic properties, infrared vibration modes, and molecular topography of hydrogen complexes, namely linear-type HCN⋯HX and T-type C2H2⋯HX (X = F, Cl, CN, and CCH). Ideally, the knowledge of the ternary systems of C2H2⋯HCN⋯HF and HCN⋯HCN⋯HF whose subparts integrate the linear and T-shaped complexes were used to give support in this current research. By means of computational calculations carried out in both levels B3LYP and MP2, the variations of the HX bond lengths are clearly overestimated in the HCN⋯HX linear complexes. In agreement with the analyses of the electrostatic potentials, the higher intermolecular energies of these complexes agree with the larger red-shifts in the stretch frequencies in HX. Also, the QTAIM descriptors and NBO calculations were used to inspect the interaction strength as well as to confirm the π cloud as a proton accepting center. By taking into account the absorption intensity ratio as a standard parameter to predict the interaction strength and intermolecular characterization, the formalism of the charge-charge flux-overlap modified (CCFO) was applied.

Theoretical identification of structural heterogeneities of divalent nickel active sites in NiMCM-41 nanoporous catalysts

This paper deals with the theoretical identification of the digrafted Ni species exchanged into the defect sites of MCM-41 using hybrid density functional theory. The nickel–siloxane clusters included seven 2T–6T rings. The 2MR and 5MR structures were found to be the least and most favorable sites to form thermodynamically. The Ni–O distances ranged from 1.69 to 1.79 A with the highest asymmetry found in 5MR. The 4MR and 5MR clusters showed also interesting intertwined nickel configurations. Overall, the QTAIM calculations revealed the transient electrostatic nature of the Ni–O bonds.

Probing the nature of the Co(III) ion in cobalamins: The ligand substitution reactions of aquacyanocobester, aquacyano(10-nitro)cobester and aquacyano(10-amino)cobester

The substitution of axially coordinated H2O in aquacyano-heptamethylcob(III)yriate (aquacyanocobester, [ACCbs]+) and its derivatives, aquacyano(10-nitro)cobester, [AC(10-NO2)Cbs]+, and aquacyano(10-amino)cobester, [AC(10-NH2)Cbs]+, in which the H at C10 of corrin is replaced by electron-withdrawing NO2 and electron-donating NH2, respectively, by a variety of anionic (N3−, NO2−, SCN−, SO32−, CN−) and neutral (imidazole, methylamine, 4-N,N-dimethylaminopyridine (DMAP)) ligands was studied in 50% isopropanol. Density Functional Theory (BP86/TZVP) and QTAIM calculations indicate that Co becomes more positive and harder as the C10 substituent is varied from NH2 to H to NO2. [AC(10-NH2)Cbs]+ and [ACCbs]+ have a similar affinity for virtually all the ligands but [AC(10-NO2)Cbs]+ has a lower affinity for the soft anions CN− and SO32−, and DMAP and imidazole, a similar affinity for MeNH2, and a much higher affinity for the harder anions SCN−, N3− and NO2−. The nature of the metal center can be modified by the electronic structure of the equatorial ligand and is a primary discriminator of the metal’s affinity for exogenous ligands. The second order rate constants kII for substitution of H2O by CN− in the three cobesters are not very different at 25°C because of a compensation effect between ΔH‡ and ΔS‡; if all three reactions had the same hypothetical ΔS‡ values then the rate constants would vary approximately in the ratio 109:106:1 as the C10 substituent is changed from NH2 through H to NO2. The compensation effect therefore masks the very significant differences in the reactivity of the metal ion towards an entering ligand. Log K and kII for the ligand substitution reactions of axially coordinated H2O in the cobalt corrins can be modified by perturbing the electronic structure of the equatorial corrin ligand, illustrating the importance of cis effects in these compounds.

N…N pnicogen bonds in Boc-DOPA-OMe

Crystal structures of Boc-DOPA-OMe in racemic and homochiral (S) form were determined and found to be similar in terms of supramolecular organization. The computation of electron density and its topological analysis provided insight into the interactions of the molecules within their crystal environments. The presence of N…N pnicogen bonds in both crystals was also predicted by QTAIM calculations, which are reported for the first time in amino acid systems.

Diversity of monomeric dioxo chromium species in Cr/silicalite-2 catalysts: A hybrid density functional study

The present paper deals with the theoretical characterization of the dioxo Cr species exchanged into the silicalite-2 structure via hybrid density functional theory with cluster models to represent the active site. The molecular models range from a simple mono silicon atom ring to more complex Cr–siloxane rings of 7T atoms. The common B3LYP and M06 density functionals were used for the calculations. The results indicate that the chemical hardness increases from a complex ring to a simple geminate type. Overall, the QTAIM calculations point to intermediate ionic–covalent nature of the Cr–oxygen bonds. An excellent correlation is found between the positive eigenvalue of the Hessian at the bond critical point with the CrO bond distance. Whereas the enthalpy change on the exchange reaction alters from −20.3 to 56.1kcal/mol at the M06/6-311+G∗ level, the binding energy lies in a shorter range of 907.5–926.6kcal/mol. As concluded from the Gibbs free energy changes on the exchange reaction with both of the methods, only the clusters of 4T size or larger would be formed spontaneously. However, M06 predicts ∼13% stronger bindings for the Cr ion. Overall, the electronic properties depend upon both the SiOCrOSi aperture size and the local configuration of the matrix. Furthermore, a fivefold coordination of Cr is accompanied with a lower ionization potential, a longer CrO distance, and a less negative charge on the terminal O atoms.

Should environmental effects be included when performing QTAIM calculations on actinide systems? A comparison of QTAIM metrics for Cs2UO2Cl4, U(Se2PPh2)4 and Np(Se2PPh2)4 in gas phase, COSMO and PEECM

Quantum Theory of Atoms-in-Molecules bond critical point and delocalisation index metrics are calculated for the actinide-element bonds in Cs2UO2Cl4, U(Se2PPh2)4 and Np(Se2PPh2)4, in gas-phase, continuum solvent (COSMO) and via the periodic electrostatic embedded cluster method. The effects of the environment are seen to be very minor, suggesting that they do not account for the differences previously observed between the experimental and theoretical QTAIM ρb and ∇2ρb for the U–O bonds in Cs2UO2Cl4. With the exception of the local density approximation, there is only a small dependence of the QTAIM metrics on the exchange–correlation functional employed.

Um Estudo Químico-quântico da Covalência Intermolecular em Sistemas Estabilizados por Ligações de Hidrogênio π∙∙∙H e N∙∙∙H: Cálculos DFT, ChelpG, NBO e QTAIM

In this work, density functional calculations at BHandHLYP/6-311++G(d,p) theoretical level of structural parameters, electronic properties and vibration modes of the C 2 H 2 ∙∙∙HCN∙∙∙HF and C 2 H 4 ∙∙∙HCN∙∙∙HF T-shaped hydrogen complexes is presented. As is well-known, the formation of these complexes is ruled by weak and strong hydrogen bonds recognized as p∙∙∙H and N∙∙∙H, respectively. In line with this interaction strength, a correlation between the structural modifications and frequency shifts was investigated, although the non-covalent character of these complexes has been unveiled through the QTAIM calculations. The absorption intensity ratios of the proton donors correlate well with the charge transfer amounts, whose values were computed through the ChelpG approach. Even by taking into account the cooperative profile of these systems, the hydrogen bond energies were determined, and actually, the values are unapproachable to be distributed in different moieties, such as punctual strong hydrogen bonds possessing covalent character, if exist. At last, the NBO calculations were applied to compute the s - and p -contributions on the hybrid orbitals in order to explain the frequency shifts on the H–C and H–F proton donor bonds. DOI: http://dx.doi.org/10.17807/orbital.v1i1.705

DFT Study of the effects of counter ions on bonding, molecular and spectral properties of pentaflourophenyl xenonium diflouride cation

The structures and properties of pentaflourophenyl xenonium diflouride cation (PFF) have been studied in their salts with 12 different counter ions using DFT calculations. The results demonstrated the huge effect of counter ion on all properties. The hybridization values, obtained from the NBO calculations, showed that xenon mostly used pure p orbital in their bonds, especially in Xe-F bond. Calculated binding energies (ΔH b) and ΔG b) indicated that the best anions for PFF are OH\(^{\bar {}}\), F\(^{\bar {}}\), BH\(_{\mathrm {4}}^{\bar {}}\) and OAc\(^{\bar {}}\). Moreover, the variations of HOMO and LUMO energies and the reactivity parameters have been investigated for all structures. The results of QTAIM calculations confirmed the covalent nature of Xe-C bond and the electrostatic nature of other xenon bonds. Finally, IR frequencies, NMR chemical shifts and NMR coupling constants were calculated to examine the effect of counter ion on the spectral properties of studied structures. The structures, bonding properties and the effect of counter ions on pentaflourophenyl xenonium diflouride salts were studied. In addition, NBO, QTAIM and population analyses were done to obtain the more insight about the structures. Finally, harmonic vibrations, NMR chemical shifts and NMR coupling constants were calculated.

Structural, Electronic Properties, Hydrogen Bonding Analyses, and Biological Activity of Two Multiple Myeloma Drugs: Lenalidomide and Pomalidomide

In this article, we made a comparative study of two multiple myeloma drugs: lenalidomide and pomalidomide. We calculated and discussed their geometries at DFT/B3LYP method. Intra-molecular hydrogen bonding in these molecules is confirmed and characterized by QTAIM calculations. Electronic parameters along with HOMO-LUMO and MESP surfaces are calculated in order to compare their chemical reactivity. The effect of structure and bonding on electronic properties and biological activities is discussed and it is established that pomalidomide is more biologically active than lenalidomide. The phenyl ring of these molecules show teratogenic effects, making a possibility of finding another new class of drugs.

Volatile Heterobimetallic Complexes from PdII and CuII β-Diketonates: Structure, Magnetic Anisotropy, and Thermal Properties Related to the Chemical Vapor Deposition of CuPd Thin Films.

A novel approach for preparing volatile heterometallic complexes for use as precursors for the chemical vapor deposition of various materials is reported. New CuPd complexes based on β-diketonate units were prepared, and their structures and compositions were determined. [PdL2 *CuL2 ] (1) and [PdL2 *Cu(tmhd)2 ] (2) (L=2-methoxy-2,6,6-trimethylheptane-3,5-dionate; tmhd=2,2,6,6- tetramethylheptane-3,5-dionate) are 1D coordination polymers with alternating metal complexes, which are connected through weak interactions between the Cu atoms and the OCH3 groups from the ligand of the Pd complexes. The volatility and thermal stability were studied using thermogravimetric and differential thermal analyses and mass spectrometry. Compound 1 vaporizes without decomposition into monometallic complexes. It exhibits magnetic anisotropy, which was revealed from the angular variations in the EPR spectrum of a single crystal. The vapor thermolysis process for 1 was investigated using mass spectrometry, allowing the process to be framed within the temperature range of 200-350 °C. The experimental data, supported by QTAIM calculations of the allowed intermolecular interactions, suggest that 1 likely exists in the gas phase as bimetallic molecules. Compound 1 proved to be suitable as a single-source precursor for the efficient preparation of CuPd alloy films with tunable Cu/Pd ratio. A possible mechanism for the film growth is proposed based on the reported data.

Microsolvation and hydration enthalpies of CaS2O3(H2O)(n) (n = 0-19) and S2O3(2-)(H2O)(n) (n = 0-16): an ab initio study.

We studied microhydrated calcium thiosulfate and its ions at the restricted Hartree-Fock RHF/6-31G* level of theory. A semiempirical molecular dynamics search of progressively more hydrated species provided lowest-energy configurations that were then fully optimized and characterized as energy minima at the RHF/6-31G* level of theory. The first solvation shell of calcium thiosulfate contains 18 water molecules, while the first solvation shell of thiosulfate ion consists of 15 water molecules. QTAIM calculations show hydrogen bonding to sulfur. At 298.15K, we estimate the total standard enthalpies of hydration for thiosulfate ion and calcium thiosulfate at infinite dilution as -301kcalmol(-1) and -335kcalmol(-1), respectively. The dissociation of hydrated calcium thiosulfate at infinite dilution is predicted to be an endothermic process with an enthalpy of 262kcalmol(-1). Based on some experimental data, the predominant form of calcium thiosulfate in solution is predicted to be the contact ion pair.

Tunable Interaction Strength and Nature of the S···Br Halogen Bonds in [(Thione)Br2] Systems

The strength and nature of the S···Br and Br···Br interactions were systematically tuned by altering the electron donor properties of the thione group. Three new halogen-bonded compounds, [(N-methylbenzothiazole-2-thione)Br2]·0.5CH2Cl2 (1), [(2(3H)-benzothiazolethione)Br2] (2), and [(2-benzimidazolethione)Br]·[Br3] (3), were synthesized and studied structurally by using X-ray crystallography and computationally by using charge density analysis based on QTAIM calculations. Analysis of the interaction strength indicated a formation of surprisingly strong S···Br halogen bonds in 1 (−104 kJ mol–1, and RBrS = 0.64) and 2 (−116 kJ mol–1, and RBrS = 0.63) with a substantial covalent contribution. The strong electron donor character of the thione ligand in 3 induced a heterolytic cleavage of the dibromine molecule and a change in the S···Br interaction nature to form a covalent bond with a high interaction energy (−147 kJ mol–1, and RBrS = 0.60).

Conformational preferences of monohydrated clusters of imidazole derivatives revisited.

We present the IR spectroscopic investigations of benzimidazole (BIM), N-methylbenzimidazole (MBIM), and their monohydrates (W1) carried out in a supersonic jet in the region of N-H, C-H, and O-H stretching fundamentals. The C-H stretching modes in the monomers were studied with the aim of identifying the C(2)H mode (the C atom between the two N atoms in the imidazole moiety) which is known to play an important role as a H-bond donor in enzymes and ionic liquids. The assignment was aided by quantum chemical calculations as well as the literature data for FTIR measurements in the matrix. The monohydrated clusters were investigated for a global comparison with previously reported conformations of hydrated imidazole and related derivatives in the gas phase, matrices, and He nanodroplets. The BIM-W1 complex showed the presence of three conformers; an N-H∙∙∙O bound conformer (A') and two O-H∙∙∙N bound conformers, tilted towards the phenyl side (A) and the imidazole side (B), respectively. Although both A' and B type conformers have been reported in the literature, our experiments identify a new conformer (conformer A) in the gas phase for the first time which has also been reported in crystal structures of histidine containing proteins. The binding energies of the three conformers were found to be of comparable magnitude, with the N-HO bound structure lying in between (∼0.02-0.04 kcal mol(-1)) the O-H∙∙∙N bound ones at the counterpoise corrected (cp) MP2/aug-cc-pVDZ level of theory. The formation of two distinct but closely related O-H∙∙∙N bound conformers (A and B) was additionally confirmed by studying the MBIM-W1 complex. Binding energies of the MBIM-W1 conformers were found to be higher than those of the analogous BIM-W1 conformers by 0.2 kcal mol(-1) at the cp-MP2/aug-cc-pVDZ level. The C(2)-H∙∙∙O or π bound water structures were not observed in the beam for monohydrated clusters of either monomer. While QTAIM calculations predicted secondary stabilization in the A type conformer by a C(4)-HO hydrogen bond, such an effect due to a possible C(2)-HO interaction was not found for conformer B. Experimentally, however, no spectral evidence was found for either the C(4)-H∙∙∙O or the C(2)-H∙∙∙O interaction.

The covalence and infrared spectra of cationic hydrogen bonds and dihydrogen bonds

A theoretical study of hydrogen bonds and dihydrogen bonds formed by ethyl cation, hydrocarbons and magnesium hydride is presented with calculations performed at the BHandHLYP/6-31G(d,p) level of theory. The structural results and IR analyses demonstrated great insights, mainly the strengthening and weakness of the CC bond of the ethyl cation and π or pseudo-π bonds, respectively. The interaction strength was measured through the supermolecule as well as by means of additional approaches. The QTAIM calculations were applied to characterize not only the intermolecular interactions but specifically the covalent character in the H + ⋯ π, H + ⋯ pseudo-π and H + ⋯ H contacts. The NBO calculations were useful to interpret the polarization on the CC bond and whether this effect is related with the bond length reduction as well as increase of charge density and frequency shifts.

NCI analysis of the interaction cation⋯π in complexes with molecular bowls derived from fullerene

A systematic study based on the non-covalent interactions (NCI) index was carried out in order to analyze the characteristics of the cation⋯π interaction in complexes formed by alkaline cations (Li+, Na+, K+, Rb+, and Cs+) and molecular bowls of increasing size, going from corannulene, C20H10, to the fully closed buckminsterfullerene, C60. For this purpose all the possible inner complexes with the cation on the bottom of the bowl were studied. SCF densities were employed at the B3LYP/6-31+G∗ level (LANL2DZ effective core potential basis set was included for Rb+ and Cs+). NCI plots allowed to visualize the characteristics of the cation⋯π interaction; showing the spatial arrangement of the interaction and locating the regions of different interaction strength. Moreover, when the comparison of NCI plot is carried out in an adequate way, an excellent correlation with the calculated complexation energies was found. Finally, in order to obtain complementary data, QTAIM calculations were carried out for several complexes, locating critical points and bond paths.

Hume-Rothery phase-inspired metal-rich molecules: cluster expansion of [Ni(ZnMe)₆(ZnCp*)₂] by face capping with Ni⁰(η⁶-toluene) and Ni(I)(η⁵-Cp*).

The novel all-hydrocarbon ligand-stabilized binuclear clusters of metal-core composition Ni2Zn7E, [(η(5)-Cp*)Ni2(ZnMe)6(ZnCp*)(ECp*)] (1-Zn, E = Zn; 1-Ga, E = Ga) and [(η(6)-toluene)Ni2(ZnCp*)2(ZnMe)6] (2; Cp* = pentamethylcyclopentadienyl), were obtained via Ga/Zn and Al/Zn exchange reactions using the starting compounds [Ni2(ECp*)3(η(2)-C2H4)2] (E = Al/Ga) and an excess of ZnMe2 (Me = CH3). Compounds 1-Zn and 1-Ga are very closely related and differ only by one Zn or Ga atom in the group 12/13 metal shell (Zn/Ga) around the two Ni centers. Accordingly, 1-Zn is EPR-active and 1-Ga is EPR-silent. The compounds were derived as a crystalline product mixture. All new compounds were characterized by (1)H and (13)C NMR and electron paramagnetic resonance (EPR) spectroscopy, mass spectrometric analysis using liquid-injection field desorption ionization, and elemental analysis, and their molecular structures were determined by single-crystal X-ray diffraction studies. In addition, the electronic structure has been investigated by DFT and QTAIM calculations, which suggest that there is a Ni1-Ni2 binding interaction. Similar to Zn-rich intermetallic phases of the Hume-Rothery type, the transition metals (here Ni) are distributed in a matrix of Zn atoms to yield highly Zn-coordinated environments. The organic residues, ancillary ligands (Me, Cp*, and toluene), can be viewed as the "protecting" shell of the 10-metal-atom core structures. The soft and flexible binding properties of Cp* and transferability of Me substituents between groups 12 and 13 are essential for the success of this precedence-less type of cluster formation reaction.

Coordination of Halide and Chalcogenolate Anions to Heavier 1,2,5-Chalcogenadiazoles: Experiment and Theory

New products of coordination of anions X– (X = F, I, PhS) to the Te atom of 3,4-dicyano-1,2,5-telluradiazole (1) were synthesized in high yields and characterized by X-ray diffraction (XRD) as the salts [(Me2N)3S]+[1-F]− (9), [K(18-crown-6)]+[1-I]− (10), and [K(18-crown-6)]+[1-SPh]−·THF (11), respectively. In the crystal lattice of 10, I atoms are bridging between two Te atoms. The bonding situation in anions of the salts 9–11 and some other adducts of 1,2,5-chalcogenadiazoles (chalcogen = S, Se, Te) and anions X– (X = F, Cl, Br, I, PhS) was studied using DFT, QTAIM, and NBO calculations, for 9–11 in combination with UV–vis, IR/Raman, and MS-ESI techniques. In all cases, the nature of the coordinate bond is negative hyperconjugation involving the transfer of electron density from X– to the heterocycles. The energy of the bonding interaction varies in a range from ∼30 kcal mol–1 comparable with energies of weak chemical bonds (e.g., internal N–N bond in organic azides) to ∼86 kcal mol–1 comparable with an ...