A theoretical investigation on the potential energy surface of CN2H rotation of the encapsulated 1-bicyclo[2.2.1]heptyldiazirine

The potential energy surface (PES) of CN₂H rotation of the encapsulated 1-bicyclo[2.2.1]heptyldiazirine (BHD) inside a molecular container: Cram’s hemicarcerand (CH) was explored using two different DFT involved ONIOM methods: B3LYP/6-31G^**//ONIOM(B3LYP/6-31G^*: AM1) and B971/6-31G^**//ONIOM(B971/6-31G^*: AM1). The free-state PES of CN₂H rotation was also calculated, respectively by B3LYP/6-31G^**//B3LYP/6-31G^* and B971/6-31G^**//B971/6-31G^* methods for comparison. The findings in this study have shown that the PES profiles differ from each other notably in the two states. In the encapsulated state the rotation barrier corresponding to the free-state conversion with the largest rotation barrier increases by about 2 kcal/mol, which has exceeded the largest rotation barrier in the free-state. The conformational preference behavior towards certain BHD isomers, which might be in better conformational compatibility with the container, has been demonstrated.     

Vibrational spectra and density functional study of propylgermane

Raman and infrared spectra of propylgermane, CH₃CH₂CH₂GeH₃, and its Ge-deuterated analog, CH₃CH₂CH₂GeD₃, were investigated in their gaseous, liquid and solid states. The normal coordinate treatment was carried out by density functional theory (DFT) calculation, using B3LYP/6-31G^* and 6-311++G^** basis sets, and the corresponding fundamental vibrations were assigned. The trans (T) and gauche (G) forms around the central C–C bond coexisted in the gaseous and liquid states and only the T form existed in the solid state. From the temperature dependent measurements of the Raman spectra in the liquid state, the enthalpy difference was found to be ΔH(T−G)=−0.36±0.02 kcalmol⁻¹ with the T form being more stable. The energy differences between the isomers obtained by DFT calculations were ΔE(T−G)=−0.46 kcalmol⁻¹ and ΔE(T−G)=−0.87 kcalmol⁻¹ by the 6-31G^* basis set and 6-311++G^** basis set, respectively.     

Further studies on the rotational barriers of Carbamates. An NMR and DFT analysis of the solvent effect for Cyclohexyl N,N-dimethylcarbamate

The solvent effect on the Gibbs energy of activation for rotation around the (C=O)–N bond in cyclohexyl N,N-dimethylcarbamate was investigated by dynamic NMR spectroscopy and density-functional theory at the B3LYP/6-311+G^** level. The experimental barriers were about 15 kcal mol⁻¹ with no appreciable variation when the solvent polarity was changed. A reaction field model was applied to theoretically mediate the solvent effect and the results were comparable to the experimental data. An analysis, based on the Onsager solvation theory, showed that the solvent effect on rotational barriers can be understood employing the total molecular dipole moment, the difference between the dipole moments of the ground and the transition state structures, or both, as appropriate.     

Prediction of geometries and interaction energies of complexes formed by small molecules using semiempirical and ab initio methods

The accuracy of the semiempirical quantum mechanics methods (AM1 and PM3), and the ab initio methods (6-31G^** and MP2/6-31G^**) in predicting intermolecular geometries and interaction energies have been evaluated by detailed studies of 17 bimolecular complexes formed by small molecules. Comparisons between calculated and experimental geometries for 12 complexes are presented. It was found that AM1 gave reasonably good predictions of the geometries of complexes such as CH₄ · CH₄, which have very weak interactions, but it is not as good as other methods in predicting intermolecular geometry for complexes where hydrogen bonding interactions play an important role. This is consistent with its inability to reproduce the charge transfer in the formation of hydrogen bonds in these complexes.

PM3 is able to predict intermolecular geometries for most complexes, including those with hydrogen bonding; its major flaw is its tendency to overestimate the strength of the interactions between hydrogen atoms. Care should be taken therefore in using PM3 to study complicated molecular systems with multiple hydrogen atom interactions and the method's weakness in handling complexes in which electrostatic forces are important should also be noted.

Among ab initio methods, both the 6-31G^** and the MP2/6-31G^** were found to outperform AM1 and PM3 in prediction of intermolecular geometry. Both of these ab initio methods showed excellent consistency in geometry prediction for most of the complexes studied, although MP2/6-31G^** is better than 6-31G^**. It is noted that the MP2/6-31G^** did not produce the correct geometry for the CO₂· HF complex.

For 12 complexes for which experimental geometry data are available, AM1, PM3, 6-31G^**, and MP2/6-31G^** successfully predicted the geometry in 10, 12, 12, and 11 cases, respectively. The average errors given by AM1 in the predicted intermolecular distances were 0.264, 0.272, 0.091, and 0.061 Å, respectively. In comparison to the ab initio methods, AM1 and PM3 commonly underestimated the molecular interaction energy in such complexes by ˜ 1–2 kcal mol⁻¹.     

Binding mechanism of RGD and its mimetics to receptor GPIIb/IIIa. A theoretical study

In order to better understand, at a sub-molecular level, the minimal structural requirements for the recognition process in the platelet aggregation inhibitory activity, a series of RGD mimetics were examined as fibrinogen receptor antagonists variants. We simulate the electronic interactions between RGD with its biological receptor in terms of smaller molecules. MeCOO⁻ was used to mimic the side chain of deprotonated Asp and Meguanidinium group mimicked the side chain of the protonated Arg. Alternative moieties present on the RGD mimetics were also studied in this report. AM1; RHF/3-21G; B3LYP/6-31++G^** in the gas phase. Also, B3LYP/6-31++G^** calculations using the IPCM solvation model were carried out for all the complexes. Our results indicate that high level of theory calculations and the inclusion of solvent effects are crucial in order to obtain satisfactory of accuracy in the electronic distributions of these compounds.     

Conformation of N,N′-bis (2,6-dimethylmorpholino), N″-dichloroacetyl phosphoric triamide: CHCl2C(O)NHP(O)[2,6(CH3)2(NC4H6O)]2. NMR and ab initio studies

Using phosphorus pentachloride as a substrate, a new carbacyclamidophosphate, N,N″-bis (2,6-dimethylmorpholino), N″-dichloroacetyl phosphoric triamide (1) has been synthesized and characterized by ¹H, ³¹P and ¹³C NMR, IR spectroscopy and elemental analysis. Due to the presence of methyl disubstituted morpholine rings and the dichloroacetamide group, several conformers can be considered for this molecule. The ³¹P{¹H} NMR spectra for the isomeric mixture of synthesized compound showed four signals with the ratio 67.1; 19.0; 12.2; 1.7, which indicates four independent conformers. The ¹H NMR spectra confirmed these results. The conformational space and the molecular geometry of the molecule in the gaseous phase have been studied using the B3LYP method of approximation, with 6-31G and 6-311++G^** basis sets.     

Molecular structure and conformational stability of allylisocyanate—post-Hartree–Fock and density functional theory studies

The molecular structure and conformational stability of allylisocyanate (CH₂CHCH₂NCO) molecule was studied using the ab initio and DFT methods. The geometries of possible conformers, C-gauche (δ=120°, θ=0°) (δ=C=C–C–N and θ=C–C–N=C) and C-cis N-trans (δ=0° and θ=180°) were optimized employing HF/6-31G^*, MP2/6-31G^* levels of theory of ab initio and BLYP, B3LYP, BPW91 and B3PW91 methods of DFT implementing the atomic basis set 6-311+G(d,p). The structural and physical parameters of the above conformers were discussed with the experimental and theoretical values of the related molecules, methylisocyanate and 3-fluoropropene. It has been found that the N=C=O bond angle is not linear as the experimental result for both the conformers and the theoretical bond angle is 173°. The rotational potential energy surfaces have been performed at the HF/6-31G^*, and MP2/6-31G^* levels of theory. The Fourier decomposition potentials were analysed at the HF/6-31G^*, and MP2/6-31G^* levels of theory. The HF/6-31G^* level of theory predicted that the C-gauche conformer is more stable than the C-cis N-trans conformer by 0.41 kJ/mol, but the MP2 and DFT methods predicted the C-cis N-trans conformer is found to be more stable than the C-gauche conformer. The calculated chemical hardness value at the HF/6-31G^* level of theory predicted the C-cis N-trans form is more stable than C-gauche form, whereas the chemical hardness value at the MP2/6-31G^* level of theory favours the slight preference towards the C-gauge conformer.     

Structure and conformational stability of CH2CHCH2X (X=F, Cl and Br) molecules—post Hartree–Fock and density functional theory methods

The molecular structure and conformational stability of CH₂CHCH₂X (X=F, Cl and Br) molecules were studied using ab initio and density functional theory (DFT) methods. The molecular geometries of 3-fluoropropene were optimized employing BLYP and B3LYP levels of theory of DFT method implementing 6-311+G(d,p) basis set. The MP2/6-31G^*, BLYP and B3LYP levels of theory of ab initio and DFT methods were used to optimize the 3-chloropropene and 3-bromopropene molecules. The structural and physical parameters of the molecules are discussed with the available experimental values. The rotational potential energy surface of the above molecules were obtained at MP2/6-31G^* and B3LYP/6-311+G(d,p) levels of theory. The Fourier decomposition of the rotational potentials were analyzed. The HF/6-31G^* and MP2/6-31G^* levels of theory have predicted the cis conformer as the minimum energy structure for 3-fluoropropene, which is in agreement with the experimental values, whereas the BLYP/6-311+G(d,p) and B3LYP/6-311+G(d,p) levels of theory reverses the order of conformation. The ΔE values calculated for 3-chloropropene at MP2/6-31G^*, BLYP/6-311+G(d,p) and B3LYP/6-311+G(d,p) levels of theory show that the gauche form is more stable than the cis form, which is in agreement with the experimental value. The same levels of theory have also predicted that the gauche form is stable than cis for 3-bromopropene molecule. The maximum hardness principle has been able to predict the stable conformer of 3-fluoropropene at HF/6-31G^* level of theory, but the same level of theory reverses the conformational stability of 3-chloropropene and 3-bromopropene molecules and MP2/6-31G^* level of theory predicted the stable conformer correctly.     

Electronic structure and conformational properties of (carboxy-alkenyl)-phosphonic acids

The general conformational properties and electronic structure of (carboxy-alkenyl)-phosphonic derivatives were determined at RHF/STO-3G^* level. In all the series, low rotation barriers were found for the two C=C/P=O conformers. In the compounds in which the interactions between the carboxylic and phosphonic moieties are smaller, the most stable conformers are the C=C/P=O s-cis ones. In most of the conformers, the C=C/C=O system presents the disposition s-cis. The Z-(2-carboxy-vinyl) and Z-(2-carboxy-propenyl) phosphonic acids present intramolecular hydrogen bonds, existing in at least four conformer with internal hydrogen bonds. These last compounds were more rigorously studied at RHF/3-21G^* and RHF/6-31G^** levels. The most stable conformer shows a trans structure for the C=C/P=O angle, with an intramolecular hydrogen bond located between the hydroxylic hydrogen of phosphonic group and the carbonyl oxygen of carboxylic moiety. A secondary conformer is found with a double intramolecular hydrogen bond between two hydroxylic hydrogens of the phosphonic moiety and the oxygen of carboxylic bond. Another secondary conformer appears with an intramolecular hydrogen bond between the oxygen of the phosphoryl bond and the hydroxylic hydrogen of the carboxylic group. A study of the topology of charge densities is carried out. This analysis reveals bonds with an ionic participation. A very weak π conjugation, variable with the conformers, is found in the C=C/P=O system, as well as a strongly polarized P=O partial triple bond. The intramolecular hydrogen bonds give rise to cyclic structures.     

Electronic structure of N-sulfonylimines

The electronic structure of N-sulfonylimines has been studied in detail using ab initio MO and density functional methods. The S–N rotational barriers in HS(O)₂N=CH₂ at G2MP2 and CBS-Q levels have been found to be 3.25 and 3.43 kcal/mol respectively. Complete optimization at HF/6-31+G^*, MP2(full)/6-31+G^* and B3LYP/6-31+G^* levels have shown that synperiplanar arrangement of S–O with respect to C=N is more stable. NBO analysis has been carried out to quantitatively estimate these delocalisations and charge polarization in RS(O)₂N=CH₂ (R=H, Me, Cl, F). The Lewis basic character in N-sulfonylimines is less compared to N-alkylimines due to anomeric interactions that reduce the lone pair electron density on nitrogen in 1.     

Spectroscopic characterization and single molecule structures of N,N-bis-(3-phthalimidopropyl)-N-(2-hydroxyethyl)-N-propylammonium salts and their hydrates

N,N-Bis-(3-phthalimidopropyl)-N-(2-hydroxyethyl)-N-propylammonium salts and their hydrates have been characterized by FTIR, Raman and NMR spectroscopy. Also B3LYP and PM5 calculations have been carried out. The optimized bond lengths, bond angles and torsion angles calculated by B3LYP/6-31G(d,p) approach have been compared with the spectroscopic data. The screening constants for ¹³C and ¹H atoms have been calculated by the GIAO/B3LYP/6-31G(d,p) approach and analyzed. Linear correlations between the experimental ¹H and ¹³C chemical shifts and the computed screening constants confirm the optimized geometry.     

A semi-empirical and ab initio combined approach for the full conformational searches of gaseous lysine and lysine–H2O complex

A full structural search of the canonical, zwitterionic, protonated and deprotonated lysine conformers in gas phase is presented. A total of 17,496 canonical, 972 zwitterionic, 11,664 protonated and 1458 trial deprotonated structures were generated by allowing for all combinations of internal single-bond rotamers. All the trial structures were initially optimized at the AM1 level, and the resulting structures were determined at the B3LYP/6-311G^* level. A total of 927 canonical, 730 protonated and 193 deprotonated conformers were found, but there were no stable zwitterionic structures in the gas phase. The most stable conformers of the canonical, protonated and deprotonated lysine were further optimized at the B3LYP/6-311++G^** level. The energies of the most stable structures were determined at the MP2/6-311G(2df,p) level and the vibrational frequencies were calculated at the B3LYP/6-311++G^** level. The rotational constants, dipole moments, zero-point vibrational energies, harmonic frequencies, vertical ionization energies, enthalpies, Gibbs free energies and conformational distributions of gaseous lysine were presented. Numerous new structures are found and the lowest-energy lysine conformer is more stable than the existing one by 1.1 kcal/mol. Hydrogen bonds are classified and may cause significant red-shifts to the associated vibrational frequencies. The calculated proton affinity/dissociation energy and gas-phase basicity/acidity are in good agreement with the experiments. Calculations are also presented for the canonical lysine–H₂O and zwitterionic lysine–H₂O clusters. Interaction between lysine and H₂O significantly affects the relative conformational stabilities. Only one water molecule is sufficient to produce the stable zwitterionic structures in gas phase. The lowest-energy structure is found to be zwitterions when applying the conductor-like polarized continuum solvent model (CPCM) to the lysine–H₂O complexes.     

Investigation of conformational stability and vibrational spectra of halomethylsulfonyl isocyanates

The conformational behavior and structural stability of chloro- and fluoromethylsulfonyl isocyanates were investigated by quantum mechanical DFT and ab initio MP2 calculations. The 6-311++G^** basis set was employed to include polarization and diffuse functions in the calculations. The molecules were found to exist in a mixture of two stable gauche conformations. The potential scans were calculated from which the rotational barriers could be estimated. The vibrational frequencies and spectra were computed at B3LYP/6-311++G^** level. The potential energy distributions were then calculated to provide tentative vibrational assignment for the normal modes of the stable conformers of both molecules.     

Ab initio studies of methanol, methanethiol and methylamine dimer

Quantum chemical calculations are used to provide structural, vibrational and energetical information on the dimers of the methanol, methylamine and methanethiol systems. These systems were studied employing the DFT(B3LYP) and MP2 methods together with the 6-31+G^** and 6-311+G^** basis sets. We found two distinct potential minima for methylamine (one of them is a transition structure) and methanethiol, and one for the methanol dimer. The properties of these dimers are compared with those of the dimers (H₂O)₂, (NH₃)₂ and (CH₃SH)₂. The interactions in these dimers were analyzed using electron density properties at the bond critical point.     

Ab initio calculations of minimum-energy pathways of the nucleophilic addition of the H anion, LiH molecule and Li/H ion pair to acetylene and methylacetylene

Ab initio calculations were performed for special points of the minimal energy pathways (MEP) of the nucleophilic addition reactions of the isolated H⁻ anion, LiH molecule and Li⁺/H⁻ ion pair to acetylene (A) and methylacetylene (MA) molecules, proceeding in accordance (M) and against (aM) the Markovnikov's rule. All structural parameters were optimized using the restricted Hartree–Fock (RHF) method. For the addition of H⁻, the 6-31++G^* basis set was used and for the reactions of LiH and Li⁺/H⁻ the 6-31G^* basis set with the subsequent recalculation of single point energies, taking into account of electron correlation energy by means of the second-order Möller–Plesset perturbation theory at the MP2/6-31++G^** level. The results of calculations demonstrate, that the energy characteristics of both M- and aM-additions with H⁻ do not differ sufficiently (0.1–1.2 kcal/mol for the activation energies (ΔE_a) and the reaction heats (ΔQ)). The substitution of the H atom by the CH₃ group in A molecule results in practically the same values of ΔQ and ΔE_a. On the contrary, for the LiH molecule and Li⁺/H⁻ ionic pair, the M-addition is favorable (charge control). It is found that the presence of electrophile decreases the activation energy by 3–5 kcal/mol as compared with the addition of the isolated hydride ion H⁻.     

Vibrational spectra and potential energy distributions for 3-cyclopropenecarboxaldehyde by density functional and normal coordinate calculations

The structural stability and internal rotation in 3-cylopropenecarboxaldehyde were investigated by ab initio calculations with 6-311++G^** basis set. The calculations were carried out at the restricted Hartree–Fock (HF) and the Density Functional B3LYP levels. The vibrational frequencies were computed at HF and DFT-B3LYP levels. Normal coordinate calculations were carried out and potential energy distributions were calculated for the cis and the trans conformers of the molecule.     

Theoretical study of azide anion addition to nonpolar and polar double and triple bonds

Transition structures for the 1,3-polar addition of azide anion to hydrogen cyanide, formaldimine, nitrogen, cis- andtrans -diazene, ethylene and acetylene were obtained at the MP2/6-31+G^* theoretical model. The additions can be divided into two groups: addition to a triple bond, giving rise to an aromatic heterocyclic product, and addition to a double bond, forming a non-aromatic product. All transition structures correspond to a concerted mechanism for the polar cycloaddition. Symmetrical dienophiles, apart from cis-diazene, give rise to synchronous transition structures. The anomaly is explained in terms of strong n-n repulsion of the reactants in the transition structure. The reactivity of the compounds can be rationalized in terms of the bond orders of the newly forming bonds, from the frontier orbital energy differences and from the charge transfer from the azide anion to the dienophile. The quantitative correlation of the reactivity has been judged on the basis of the activation energies of the reactions calculated at MP2/6-31+G^* and MP3/6-31+G^*. It is predicted that the addition of azide to nitrogen is the slowest and that the additions to hydrogen cyanide and acetylene have the lowest barriers, in agreement with literature data.     

An ab initio SCF study on the tautomerisation of the 8-oxo-guanine and xanthine

All possible H₉-tautomers of 8-oxo-guanine and xanthine were studied by means of PM3 semiempirical and DFT (density functional theory) quantum chemistry methods. Additionally, the five most stable tautomers of both guanine derivatives were estimated on 3-21G, 6-31G, 6-31G^** and MP2 (6-31G^**) ab initio levels. The impact of the environment polarity on the tautomeric equilibrium was also taken into account. Among the variety of tautomeric isomers most probable are diketo forms of both studied derivatives in non-polar and polar surroundings.

The tautomeric equilibrium was unchanged after connection of the sugar backbone. The most preferred diketo forms of 8-oxo-guanosine and xanthidine are in syn conformations both in polar and non-polar environments. The increase of the syn conformations over anti ones may have the source in the formation of the internal hydrogen bonds between H′5 and N₃ atoms. The calculated values of the pseudorotation phase angle were between 144 and 180° in all cases. This corresponds to C′2-endo conformations of all optimised structures.

The N-glycosidic bond stability of most stable tautomers was compared to standard guanosine. Most tautomers of 8-oxo-guanosine and xanthidine are characterised by more stable C₁′-N₉ bond. This indicates that both these derivatives are hardly susceptible to spontaneous depurination and its removal from the DNA will depend mostly on the activity of DNA repair enzymes.     

Proton affinity of uracil. A computational study of protonation sites

Relative stabilities of uracil tautomers and cations formed by gas-phase protonation were studied computationally with the B3LYP, MP2, QCISD, and QCISD(T) methods and with basis sets expanding from 6-31G(d,p) to 6-311+G(3df,2p). In accordance with a previous density functional theory study, the dioxo tautomer 1a was the most stable uracil isomer in the gas phase. Gibbs free energy calculations using effective QCISD(T)/6-311+G(3df,2p) energies suggested >99.9% of 1a at equilibrium at 523 K. The most stable ion isomer corresponded to N-1 protonated 2,4-dihydroxypyrimidine, which however is not formed by direct protonation of 1a. The topical proton affinities in 1a followed the order O-8 > O-7 > C-5 > N-3 > N-1. The thermodynamic proton affinity of 1a was calculated as 858 kJ mol⁻¹ at 298 K. A revision is suggested for the current estimate included in the ion thermochemistry database.     

Structure and stability of ammonium-sulfate and guanidium-sulfate complex

Ab initio (HF/6-31G^** and B3LYP/6-31 + + G^**) methods have been used to study the stability and structure of complexes between CH₃SO⁻₃ and CH₃NH⁺₃ or C(NH₂)⁺₃. Results show that no hydrogen jump is involved in the complex formations, which is different from previous work studying complexes between CH₃COO⁻ and CH₃NH⁺₃. In addition, we have studied complexes between CH₃SO⁻₃ and HC(NH₂)⁺₃ or ⁺H₃NC(NH₂)₃, all of which have a cage structure.