Natural Bond Orbital Approach Research Articles

Accurate Structure and Dynamics of the Metal-Site of Paramagnetic Metalloproteins from NMR Parameters Using Natural Bond Orbitals

A natural bond orbital (NBO) analysis of unpaired electron spin density in metalloproteins is presented, which allows a fast and robust calculation of paramagnetic NMR parameters. Approximately 90% of the unpaired electron spin density occupies metal–ligand NBOs, allowing the majority of the density to be modeled by only a few NBOs that reflect the chemical bonding environment. We show that the paramagnetic relaxation rate of protons can be calculated accurately using only the metal–ligand NBOs and that these rates are in good agreement with corresponding rates measured experimentally. This holds, in particular, for protons of ligand residues where the point-dipole approximation breaks down. To describe the paramagnetic relaxation of heavy nuclei, also the electron spin density in the local orbitals must be taken into account. Geometric distance restraints for 15N can be derived from the paramagnetic relaxation enhancement and the Fermi contact shift when local NBOs are included in the analysis. Thus, the NBO approach allows us to include experimental paramagnetic NMR parameters of 15N nuclei as restraints in a structure optimization protocol. We performed a molecular dynamics simulation and structure determination of oxidized rubredoxin using the experimentally obtained paramagnetic NMR parameters of 15N. The corresponding structures obtained are in good agreement with the crystal structure of rubredoxin. Thus, the NBO approach allows an accurate description of the geometric structure and the dynamics of metalloproteins, when NMR parameters are available of nuclei in the immediate vicinity of the metal-site.

A theoretical study on the inclusion complexation of doxycycline with Crysmeb

Abstract The geometry of the inclusion complexes of 2-O-methyl-beta-cyclodextrin (called MeβCD or Crysmeb) with the two tautomers (enol and keto) isomer of doxycycline (DOX) in the gas phase, is determined using PM6 and ONIOM2 calculations with [B3LYP/6-31G(d):HF/3-21G*] level. Inclusion process pathways are described and the most probable structure of the 1:1 complex is sought through a potential energy scan using the PM6 method. Within the ONIOM2 procedure two levels of calculation are defined: B3LYP/6-31G(d) for DOX and the HF/3-21G* level for Meβ CD. The geometry of the most stable complex in the keto or enol forms obtained with the two methods, in which the aromatic ring is included inside the hydrophobic cavity of Crysmeb. The energetic differences between the two forms are 0.17 and 6.27 kcal/mol, respectively with PM6 and [B3LYP/6-31G(d):HF/3-21G*] calculations. These energies also include ZPE corrections. The energetically more favorable structure obtained with the ONIOM2 method leads to the formation of six intermolecular H-bonds between DOX and Crysmeb, i.e. three conventional H-bonds, one between the oxygen atom (O197) of the OH bond of DOX and the hydrogen atom (H140) of Crysmeb and the second between oxygen atom (O53) and a hydrogen atom (H218) of the hydroxyl group of DOX. The last one is between the oxygen atom (O73) and a hydrogen atom (H214) of the hydroxyl group of DOX. These H-bond are assisted by three weak H-bonds of type ( C-H ⋯ O ). All these interactions were investigated using the Natural Bond Orbital (NBO) approach.

Computational studies of 1:2 complex between retinol propionate and β cyclodextrin

[M05-2X/6-31G*:PM3MM] and [B3LYP/6-31G*:PM3] ONIOM2 methods have been used to investigate the vitamin A propionate/β cyclodextrin complex with 1:2 stoichiometry. Both methods give almost the same lowest energy minimum. The minimum energy structure of the complex is found in good agreement with experimental data. In this configuration, the major structure of propionate of vitamin A (PVA) is embedded inside the two cavities of βCD while the propionate group is kept outside. However, the three methyl groups of PVA are positioned in the free space between both βCD molecules. The driving forces for complexation are dominated by Van der Waals interactions between PVA and the βCD molecules assisted with multiple hydrogen bond interactions between the two cyclodextrin molecules. These interactions were investigated using the natural bond orbital approach.

Cation–π interactions: Complexes of guanidinium and simple aromatic systems

We have theoretically studied, in gas phase and using PCM-water solvation, the complexes established by the biologically relevant guanidinium cation and simple aromatic systems (benzene, naphthalene and pyridine). In gas phase only hydrogen bonded complexes were obtained, whereas using PCM-water different cation–π complexes for the three aromatic systems were found. The interactions established within these complexes have been analyzed by means of the atoms in molecules and natural bond orbital approaches. Finally, experimental evidence of the cation–π interactions created by guanidinium was found in the crystal structure of N-(5-methylpyridin-2-yl)guanidinium chloride, which was also theoretically analyzed.

From Inert to Explosive, The Hydrolytic Reactivity of R−NSO Compounds Understood: A Computational Study

We present a computational study on the concerted hydrolysis of several classes of N-sulfinylamines of generic formula R-N═S═O, such as the -amines themselves (R-NSO), -hydrazines (R-NH-NSO), -hydrazides (R-CO-NH-NSO) and -amides (R-CO-NSO), as these species are known to possess a wide range of hydrolytic reactivity. Two possible mechanisms of hydrolysis, with a water dimer across the S═O and N═S bonds, in the gas phase are investigated. The reactivity is discussed with respect to the electronic structures, established with the use of the quantum theory of Atoms in Molecules, Natural Bond Orbital and Natural Resonance Theory approaches. For the inert N-sulfinylhydrazines and the keto tautomers of N-sulfinylhydrazides, extended π-conjugation adds a sulfide-like resonance structure that is responsible for their insensitivity toward moisture. Activation barriers for hydrolysis, where water acts as a nucleophilic reagent, decrease with increasing positive charge on the NSO sulfur atom, a finding that might prove useful as a predictive tool in the determination of the general reactivity of an N-sulfinyl compound by experimentalists.

The structure of mono- and di-amino derivatives of cyclohexane: Energetic and Natural Bond Orbital approaches

A full exploration of the conformational space of mono and di-amino derivatives of cyclohexane have been performed using the second-order Møller-Plesset approximation method (MP2) and the aug-cc-pVDZ basis set. These data were further complemented by the application of the Natural Bond Orbital (NBO) theory. The population of the equatorial conformers was found to be 84% in cyclohexylamine (CHA), varying from 94% to 99% in the cyclohexyldiamine isomers (CHDA). Based on the weighed mean energies computed for the different CHDA isomers, the following energetic sequence has been established: t12<c12<t14≈c13<c14≈t13. The results given by the MP2 calculations were discussed in terms of pairwise steric repulsions between filled orbitals and electron delocalization from filled to vacant orbitals provided by the NBO analysis. With the exception of the vicinal isomers, the former interactions were found to be the most important factor for the conformers/isomers stabilization. Attention was also given to the role played by the syn-1,3-di-axial repulsions in the destabilization of the axial conformers of CHA. An intramolecular hydrogen bond was found to stabilize the di-axial conformers of c13CHDA.

Sigma- and pi- electron structure of aza-azoles

The reasons behind changes of aromaticity in 10 unsubstituted aza-azoles were analysed by employing the natural bond orbital (NBO) approach at the MP2/6-311+G(d,p) level of theory. Sum of occupations of p(z) orbitals at atoms in the ring correlates well with the magnetism based aromaticity index NICS as well as with the number of nitrogen atoms in the ring. Changes of NICS depend strongly in a linear way on the number of NN bonds. Classification of azoles based on the number of pyridine-type nitrogen atoms vicinal to NH is supported by plotting the relative occupation of π orbitals (π(occ)) against the relative occupation of σ orbitals (σ(occ)) for all individual atoms in rings.

Theoretical Study of Bis(phenylethynyl)thienoacenes as Precursors of Molecular Wires for Molecular Electronics

The geometries and electronic properties of a series of bis(phenylethynyl)thienoacenes as precursors of n-type materials with desirable (opto)electronic properties have been studied from a theoretical perspective: 2,5-bis-phenylethynyl-thiophene (PhEtT), 2,5-bis-phenylethynyl-thieno[3,2-b]thiophene (PhEtT2), 2,6-bis-phenylethynyl-dithieno[3,2-b;2′,3′-d]thiophene (PhEtT3), and 2,6-bis-phenylethynyl-3,4,7,8-tetrathia-dicyclopenta[a,e]pentalene (PhEtT4). This has allowed performance of a comparative study of the influence of the number of fused thiophene rings on the studied properties. The (opto)electronic properties and conducting capability were investigated through the HOMO → LUMO excitation energy, bond length alternation (BLA), LUMO energy, electron affinity, and intramolecular reorganization energy. Also, the influence of planarity on electrical conductivity has been analyzed by means of the natural bond orbital (NBO) approach together with the theory of atoms in molecules (AIM). From this study it follows that the increase in the number of fused thiophene rings does not significantly affect those properties related to aromaticity such as BLA, rotational barriers, or charge transference between the different aromatic rings, while that increase leads to an easier charge injection and brings on an enhancement of the n-type character.

Natural bond orbital approach to the transmission of substituent effect through the fulvene and benzene ring systems

Electronic structure of 22 monosubstituted derivatives of benzene and exocyclically substituted fulvene with substituents: B(OH)(2), BH(2), CCH, CF(3), CH(3), CHCH(2), CHO, Cl, CMe(3), CN, COCH(3), CONH(2), COOH, F, NH(2), NMe(2), NO, NO(2), OCH(3), OH, SiH(3), SiMe(3) were studied theoretically by means of Natural Bond Orbital analysis. It is shown, that sum of π-electron population of carbon atoms of the fulvene and benzene rings, pEDA(F) and pEDA(B), respectively correlate well with Hammett substituent constants [Formula in text] and aromaticity index NICS. The substituent effect acting on pi-electron occupation at carbon atoms of the fulvene ring is significantly stronger than in the case of benzene. Electron occupations of ring carbon atoms (except C1) in fulvene plotted against each other give linear regressions with high correlation coefficients. The same is true for ortho- and para-carbon atoms in benzene. Positive slopes of the regressions indicate similar for fulvene and benzene kind of substituent effect - mostly resonance in nature. Only the regressions of occupation at the carbon atom in meta- position of benzene against ortho- and para-positions gives negative slopes and low correlation coefficients.

Quantum mechanical study of the structure and spectroscopic characterisation of the novel trisilylsilylcyanide and trigermylgermylcyanide in the gas phase

Quantum mechanical methods have been employed to investigate the structural and spectroscopic properties of the novel trisilylsilylcyanide and trigermylgermylcyanide isolated molecules, in C 3v symmetry, in the gas phase. The levels of theory used are DFT and MP2, the functional employed for the DFT method is B3LYP and the basis set used for all atoms is 6-311G(d, p). En route, the structures of these compounds have been analysed using the natural bond orbital approach. The latter confirms the presence of all single bonds and the only triple bond, namely, the C N bond, in both of these molecules. Substituting silicon and germanium for carbon in the parent molecule, trimethylmethylcyanide, leave the bond length C N almost invariant. Both the ab initio methods used perform satisfactorily when the predicted parameters from the two methods are compared. All the normal modes of vibrations were assigned to one of the 11 types of motion namely X–C stretch, X–X stretch, C N stretch, X–H stretch, X–X–C bend, X–X–X bend, X–C N bend, H–X–H bend, XH 3 rock, XH 3 def and XH 3 twist (X = Si or Ge). An interesting outcome of this work is that the HOMO–LUMO energy gap decreases from trimethylmethylcyanide to trigermylgermylcyanide. Since these compounds have not yet been synthesised, we have successfully compared the predicted parameters with related molecules for which results have been published in the literature.

Molecular model of CENS piperidine β-CD inclusion complex: DFT study

Abstract Structural aspects of the complexation of N-nitroso-N’-(2-chloroethyl)-N’-sulfamide piperidine (CENS) with β-cyclodextrin (β-CD) were investigated using standard B3LYP and MPW1PW91 Density Functional Theory (DFT) calculations. Two orientations of the incoming CENS inside β-CD were considered to determine the lowest energy complex, namely the head (ring first) and tail (chain first) orientations. The calculations confirm that the tail orientation is more favorable than the head one by 5.9 kcal/mol (B3LYP) and 5.9–6.1 kcal/mol (MPW1PW91) the driving factor being the deformation energy undergone by β-CD. This preference is also due to the fact that the complexation with tail orientation of CENS occurs with a favourable anti-parallel disposition of the dipole moments of β-CD and CENS. The computed structure for the CENS – β-CD complex is in good agreement with mass and 15 N NMR spectroscopy observations. Moreover, this complexation mode leads to the formation of four intermolecular H-bonds between CENS and CD, i.e. two conventional H-bonds, one between N atom (N136) of the NO bond of CENS and H 6 O atom (H129) of β-CD and the other one between O atom (O137) of CENS SO 2 group and H 6 O (H120) and two weak (C H…O) bonds. These interactions were investigated using the Natural Bond Orbital (NBO) approach.

Theoretical study of the structural, spectroscopic and energetic properties of difluoro(germylthio)phosphine and difluoro(germylseleno)phosphine in the gas phase

Theoretical methods have been employed to investigate the structural, spectroscopic and energetic properties of difluoro(germylthio)phosphine in the C s symmetry in the gas phase. The levels of theory used are MP2 and DFT/B3LYP and the basis set used for all atoms is 6-311G(d,p). The computed structural parameters, namely, bond lengths and bond angles and spectroscopic parameters, namely, infrared frequencies, Raman activities and NMR chemical shifts have been compared with experimental data reported in literature. The structure of this compound has been analysed using natural bond orbital approach. Both the ab initio methods perform satisfactorily when the predicted and experimental parameters are compared. We have extended this study, using the same methods and basis set, to the selenium analogue, namely, difluoro(germylseleno)phosphine for which literature is elusive. The MP2/6-311G(d,p) geometrical parameters for difluoro(germylseleno)phosphine are: r(P–Se) = 2.270, r(Ge-Se) = 2.386, r(P–F) = 1.604, r(Ge–H) = 1.530 Å, ∠(Ge–Se–P) = 91.4, ∠(F–P–F) = 96.7, ∠(Se–P–F) = 99.9 and ∠(Se–Ge–H) = 109.5°. Apart from these, we have also studied the energetic parameters for their synthesis. The results indicate that formation of the sulphur-containing compound is favoured thermodynamically.

On the nature of copper–hydrogen bonding: AIM and NBO analysis of CuHn (1 ≤ n ≤ 6) complexes

AbstractAn analysis of copper–hydrogen interactions of six minima and one transition state on the CuHn potential energy surfaces was done using Atoms in Molecules theory and Natural Bond Orbital approach with UB3LYP/DGDZVP wave functions. We localized one minimum on all CuHn potential energy surfaces (PESs) with the exception of the PES with n = 3. This PES has two symmetrical minima and one transition state. The CuHn complexes with n = 1, 3, and 5 have a monohydride fragment. Those with even number of hydrogens have a dihydride fragment. The remaining H atoms are coordinated as (H2) to CuH or to HCuH. The copper–hydrogen interactions were classified as closed shell (CS) and the HH bonds as shared shell using the Laplacian of ρ(r). When it was considered the |V(r)|/G(r) ratio, we could split the copper–hydrogen interactions into pure CS and transit CS. Taking into account the magnitude of the H(r), the transit CS copper–hydrogen interactions can be divided into dative and metallic. On the other hand, according to the NBO analysis, the copper–H2 interactions can be classified as synergistic and dative H2 coordination types. © 2009 Wiley Periodicals, Inc. Int J Quantum Chem, 2010

Theoretical investigation of electronic structures and excitation energies of hexaphyrin and its group 11 transition metal (III) complexes

Density functional theory is carried out to study hexaphyrin and its bis-metal and mixed bis-metal (M = Cu 3+, Ag 3+, and Au 3+) complexes. The electronic structures and bonding situations of them are studied by using natural bond orbital approach and the topological analysis of the electron localization function. Electronic spectra are investigated by using time-dependent density functional theory. The introduction of group 11 transition metals leads to red shifts in the spectra of these metal complexes with respect to that of hexaphyrin. Moreover, it is noteworthy that the spectra of copper contained complexes are mainly derived from combination of ligand-to-metal charge transfer and ligand-to-ligand charge transfer transitions. In addition, the relativistic time-dependent density functional theory with spin–orbit coupling calculations indicate that the effects of spin–orbit coupling on the excitation energies are so small that it is safe enough to neglect spin–orbit coupling for these systems.

A localized picture of back bonding in CH 3−nX n (X = F, Cl and Br; n = 1, 2 or 3) radical and cation systems

The electronic structure of back bonding in CH 3− n X n cation and radicals (X = F, Cl and Br; n = 1, 2 or 3) has been studied using the B3LYP approach. The Natural Bond Orbital (NBO) approach presents some limitations, particularly, when there are multi-identical C–X bonds in di- or tri-halogenated cation species, because it does not show back bonding in all C–X bonds simultaneously, especially in cations, although experimental and theoretical methods such as Quantum Theory of Atoms In Molecules (QTAIM) parameters confirm the existence of back bonding for multi-identical C–X bonds in the di- and tri-halogenated species. We will show that NBO is not a proper tool for such systems. Hence, Natural Localized Molecular Orbital (NLMO) procedure is suggested in this paper to remove this trouble, qualitatively. In some radical species, it is found that the carbon atom can establish two or three π back bondings with either halogen atoms in the same configuration, which resembles delocalized electronic structure. Finally, NLMO can detect π back bonding in both cation and radical species.

Stereochemical dependence of NMR geminal spin–spin coupling constants

In this work it was sought to explore the versatility of geminal spin-spin coupling constants, (2)J(XY) SSCCs, as probes for stereochemical studies. A set of compounds, where their experimental (2)J(XY) SSCCs through the X-C-Y molecular fragment are predicted to be sensitive to hyperconjugative interactions involving either bonding or antibonding orbitals containing the C carbon atom ('coupling pathway'), were analyzed. SSCC calculations were performed for some selected examples using the second order polarization propagator approximation (SOPPA) method or within the DFT-B3LYP framework. Hyperconjugative interactions were calculated within the Natural Bond Orbital (NBO) approach. Results are condensed in two qualitative rules: Rule I(M)-hyperconjugative interactions transferring charge into the coupling pathway yield a positive increase to the Fermi contact (FC), contribution to (2)K(XY) reduced spin-spin coupling constants (RSSCC), and Rule II(M)-hyperconjugative interactions transferring charge from the coupling pathway yield a negative increase to the FC contribution to (2)K(XY) RSSCC.

H-Bonded Complexes of Aniline with HF/F−and Anilide with HF in Terms of Symmetry-Adapted Perturbation, Atoms in Molecules, and Natural Bond Orbitals Theories

The hydrogen-bonded isoelectronic complexes of aniline with HF/F- and an ionic form of aniline with HF were investigated by use of computational methods: Symmetry-Adapted Perturbation Theory (SAPT), Atoms in Molecules (AIM), and Natural Bond Orbitals (NBO) approaches. All computations were based on structural models previously generated at the B3LYP/6-311+(d,p) level. The differences between neutral (Ph-NH2...HF)and anionic (Ph-NH2...F- and Ph-NH-...HF) complexes were clearly outlined. The discussed charged complexes serve as Lewis acids and base, HF and F-, respectively. It was found that electrostatic and induction energy terms, obtained as a result of the SAPT method, are most dependent on the type of H-bonding (i.e.,charged or neutral). The electrostatic term is the most distinctive between the neutral and charge-assisted hydrogen bonds in the investigated two-body systems, whereas the latter is more significant in the case of weaker interactions (larger H...B distances). Application of Principal Component Analysis (PCA) to energy components obtained from the SAPT procedure indicated that all of them are relatively well intercorrelated.The above-mentioned terms together with the exchange energy terms are the most important contributions ofthe main principal component, which describes 95% of the total variance. Comparison of AIM parameters in bond critical points for modeled H-bond systems shows a good agreement with those from equilibrium complexes, both experimental and calculated ones. It was found that charged H-bonded complexes exhibit larger fluctuation of electron density and its Laplacian in bond critical points, in line with SAPT analysis. NBO results confirmed the effect of the strength of interaction on property changes both in the region of H-bonding and outside of it. The latter, more distant consequences follow the Bent-Walsh rule for all studied complexes.

Structural property investigations of 1-[2-(2-methoxyphenyl)ethyl]piperidinium chloride: An experimental and computational study

A phenethyl containing piperidinium compound was synthesized and the results of an X-ray crystallographic and computational analysis of this compound are reported. The compound, 1-[2-(2-methoxyphenyl)ethyl]piperidinium chloride, contains a C–H···O contact, which stabilizes the experimentally found conformation. Additionally, an ionic bond between N–H···Cl atoms is present as shown by the crystallographic measurements. The presence of these two contacts prompted us to perform further theoretical studies. The first part of the computational investigations was carried out on the basis of the Car-Parrinello molecular dynamics (CPMD) in the solid-state using experimental parameters and conditions as a starting point of the simulation. The time evolution of the interatomic distances of the atoms involved in the N–H···Cl interaction was investigated. Vibrational features of the compound were studied by predicted and power spectra. In addition, static models, based on density functional theory (DFT) and second-order Møller-Plesset perturbation calculus, were built to describe the geometric and electronic structure parameters. Finally, the details of the ionic bridge were analyzed using the natural bond orbitals (NBO) approach. The electron density topology was investigated by the atoms in molecules (AIM) theory. In summary, the ionic bridge modifies the spectroscopic properties of the bridge proton. The negative charge of the chloride anion is partially delocalized via the ammonium moiety to the organic subunit.

Is There a General Rule for the Gauche Effect in the Conformational Isomerism of 1,2-Disubstituted Ethanes?

The stabilities of the gauche and anti conformations of butane, 1,2-dicyanoethane (DCE), and 1,2-dinitroethane (DNE) have been investigated through theoretical calculations. The gauche effect-the tendency of keeping close vicinal electronegative substituents (thetaX-C-C-X approximately 60 degrees ) in an ethane fragment-is expected to drive the conformational equilibrium of DCE and DNE toward the gauche conformation. It was found that, for butane, where the gauche effect is supposed to be poor/null, the hyperconjugation effect contributes mostly to the anti stabilization in opposition to the traditional sense that the methyl groups repel each other, and this should govern its conformational equilibrium. For DCE the equilibrium was shifted to the anti conformer, essentially due to a gauche repulsion, while for DNE, despite the higher electronic delocalization energies, a predominance of the gauche conformer was obtained, and this was attributed mainly to the attractive dipolar interaction between the two nitro groups. A full orbital energy analysis was performed using the natural bond orbital approach, which showed that bond bending and anti-C-H/C-X* hyperconjugation models, usually applied to explain the origin of the gauche effect in fluorinated derivatives, are not adequate to completely explain the conformational behavior of the titled compounds.

Theoretical investigation on charge‐assisted halogen bonding interactions in the complexes of bromocarbons with some anions

AbstractA series of dimeric complexes formed between bromocarbon molecules and two anions (Br−and CN−) have been investigated by using MP2 method. The quantum theory of atoms in molecules (QTAIM) and the second‐order perturbation natural bond orbital (NBO) approaches were applied to analyze the electron density distributions of these complexes and to explore the nature of charge‐assisted halogen bonding interactions. As anticipated, these interactions are significantly stronger relative to the corresponding neutral ones. The results derived from ab initio calculations described herein reveal a major contribution from the electrostatic interaction on the stability of the systems considered. Beside the electrostatic interaction, the charge‐transfer force and the second‐order orbital interaction also play an important role in the formation of the complexes, as a NBO analysis suggested. The presence of halogen bonds in the complexes has been identified in terms of the QTAIM methodology, and several linear relationships have been established to provide more insight into charge‐assisted halogen bonding interactions. © 2007 Wiley Periodicals, Inc. Int J Quantum Chem, 2008