Self-consistent Reaction Field Calculations Research Articles

DFFR: A New Method for High-Throughput Recalibration of Automatic Force-Fields for Drugs.

We present drug force-field recalibration (DFFR), a new method for refining of automatic force-fields used to represent small drugs in docking and molecular dynamics simulations. The method is based on fine-tuning of torsional terms to obtain ensembles that reproduce observables derived from reference data. DFFR is fast and flexible and can be easily automatized for a high-throughput regime, making it useful in drug-design projects. We tested the performance of the method in a few model systems and also in a variety of druglike molecules using reference data derived from: (i) density functional theory coupled to a self-consistent reaction field (DFT/SCRF) calculations on highly populated conformers and (ii) enhanced sampling quantum mechanical/molecular mechanics (QM/MM) where the drug is reproduced at the QM level, while the solvent is represented by classical force-fields. Extension of the method to include other sources of reference data is discussed.

Nature of transients produced on hydrogen atom transfer from capsaicin

Structure and energies of capsaicin and its probable transients formed in oxidation processes (single electron transfer and hydrogen atom transfer) have been investigated using theoretical calculations. Molecular geometries and energies of truncated and complete capsaicin structures have been optimized using density functional theory (DFT) with Becke three-parameter Lee-Yang-Parr (B3LYP) functional and 6–31[Formula: see text]G(d) basis set. The stable geometries have been confirmed by vibrational analysis. The calculations suggest that single-electron transfer takes place at phenolic O-atom in the first step followed by delocalization of positive charge over the whole molecule. Further, the first step of hydrogen atom abstraction should take place at phenolic group due to lowest dissociation energy but post-optimization bond dissociation energy is least for benzylic group in the side chain as compared to other transients. Effect of water as a solvent on the energies has also been studied using self-consistent reaction field calculation. Similar results are obtained for truncated and complete capsaicin structures. The present study also includes Mulliken spin, charge, vibrational frequencies and assignments of frequencies of the transients. The present study provides explanation for the observation of phenoxyl radical in fast kinetic studies using pulse radiolysis study and, formation of breakdown and dimeric products in other studies.

Theoretical and vibrational study of N-(3-chloro-4-fluoro-phenyl)-7-methoxy-6-(3-morpholin-4-ylpropoxy)-quinazolin-4-amine (gefitinib)

N-(3-chloro-4fluoro-phenyl)-7-methoxy-6-(3-morpholin-4ylpropoxy)-quinazolin-4-amine (GEF), a quinalizoline derivative used as new anti-cancer agent, designed to target activity of epidermal growth factor receptor (EGFR) promoting the growth, division and spread of cancer cells, was examined from the vibrational and theoretical point of view. All calculations have been carried out both in gaseous and aqueous phases. In the calculations of both phases, the molecule has been optimized through conformer analysis beginning with the x-ray data. The conformer analyses have been carried out in each phases and the geometrical differences between the most stable structures in gaseous and in aqueous phases have been discussed. The solvent effect for GEF in aqueous solution was simulated by using self-consistent reaction field (SCRF) calculations employing the integral equation formalism variant (IEFPCM) model. NBO analysis has been performed to indicate the presence of intramolecular charge transfer. The complete assignments of the vibrational spectra (IR&Raman) were made with the aid of calculated spectra both in gaseous and aqueous phases. The observed spectral data of the title compound were compared with the calculated spectra obtained by DFT/B3LYP and DFT/B3PW91 methods using 6-31G(d,p) basis set. The theoretical results were found to be in good agreement with the measured experimental data especially for the interpretation of intra molecular interactions.

Prediction of the pKa's of aqueous metal ion +2 complexes.

Aqueous metal ions play an important role in many areas of chemistry. The acidities of [Be(H2O)4](2+), [M(H2O)6](2+), M = Mg(2+), Mn(2+), Fe(2+), Co(2+), Ni(2+), Cu(2+), Zn(2+), Cd(2+), and Hg(2+), and [M(H2O)n](2+), M = Ca(2+) and Sr(2+), n = 7 and 8, complexes have been predicted using density functional theory, second-order Møller-Plesset perturbation theory (MP2), and coupled cluster CCSD(T) theory in the gas phase. pKa's in aqueous solution were predicted by using self-consistent reaction field (SCRF) calculations with different solvation models. The most common binding motif of the majority of the metal +2 complexes is coordination number (CN) 6, with each hexaaquo cluster having reasonably high symmetry for the best arrangement of the water molecules in the first solvation shell. Be(2+) is tetracoordinated, but a second solvation shell of 8 waters is needed to predict the pKa. The Ca(2+) and Sr(2+) aquo clusters have a coordination number of 7 or 8 as found in terms of the energy of the reaction M(H2O)7(2+) + H2O → M(H2O)8(2+) and the pKa values. The calculated geometries are in reasonable agreement with experiment. The SCRF calculations with the conductor-like screening model (COSMO), and the conductor polarized continuum model (CPCM) using COSMO-RS radii, consistently agree best with experiment at the MP2/aug-cc-pVDZ and CCSD(T)/aug-cc-pVDZ levels of theory. The CCSD(T) level provides the most accurate pKa's, and the MP2 level also provides reliable predictions. Our predictions were used to elucidate the properties of metal +2 ion complexes. The pKa predictions provide confirmation of the size of the first solvation shell sizes. The calculations show that it is still difficult to predict pKa's using this cluster/implicit solvent approach to better than 1 pKa unit.

Spectroscopic and structural studies on lactose species in aqueous solution combining the HATR and Raman spectra with SCRF calculations

In this work, the α and β isomers, the α-lactose monohydrate and dihydrate and the dimeric species of lactose were studied from the spectroscopic point of view in gas and aqueous solution phases combining the infrared, Horizontal Attenuated Total Reflectance (HATR) and Raman spectra with the density functional theory (DFT) calculations. Aqueous saturated solutions of α-lactose monohydrate and solutions at different molar concentrations of α-lactose monohydrate in water were completely characterized by infrared, HATR and Raman spectroscopies. For all the species in solution, the solvent effects were studied using the solvation polarizable continuum (PCM) and solvation (SM) models and, then, their corresponding solvation energies were predicted. The vibrational spectra of those species in aqueous solution were completely assigned by employing the Scaled Quantum Mechanics Force Field (SQMFF) methodology and the self-consistent reaction field (SCRF) calculations. The stabilities of all those species were studied by using the natural bond orbital (NBO), and atoms in molecules (AIM) calculations.

Structural and vibrational investigation on species derived from the cyclamic acid in aqueous solution by using HATR and Raman spectroscopies and SCRF calculations

In this study, aqueous solutions at different molar concentrations of sodium cyclamate in water were completely characterized by HATR (Horizontal Attenuated Total Reflectance) and Raman spectroscopies. The theoretical structures of cyclamate ion, the zwitterionic and neutral forms of the cyclamic acid and its dimer were optimized in gas and aqueous solution phases by using the hybrid B3LYP/6-31G* method. The solvent effects for the four species in aqueous solutions were simulated by using self-consistent reaction field (SCRF) calculations employing the integral equation formalism variant (IEFPCM) model. The complete assignments of the vibrational spectra of all the forms of cyclamic acid were performed taking into account the factor group analysis with the Scaled Quantum Mechanics Force Field (SQMFF) methodology. The existence of the zwitterionic and neutral forms of the cyclamic acid and its dimer in a solution of cyclamate in water is evidenced by characteristic bands in the HATR and Raman spectra. The dimerization of cyclamate in aqueous solution was previously reported by conductimetric method. The natural population analysis (NPA) and Merz–Kollman (MK) charges, molecular electrostatic potential (MEP), natural bond orbital (NBO) and atoms in molecules (AIM) calculations predict for all the species the principal donor and acceptor sites for the H bonds formation in aqueous solution. The SQM force fields for the cyclamate ion, the zwitterionic and neutral species of the cyclamic acid were obtained and their corresponding force constants in both phases were reported. Additionally, the solvation energies for those species were reported.

Electronic excitation spectra of molecules in solution calculated using the symmetry-adapted cluster-configuration interaction method in the polarizable continuum model with perturbative approach

A perturbative approximation of the state specific polarizable continuum model (PCM) symmetry-adapted cluster-configuration interaction (SAC-CI) method is proposed for efficient calculations of the electronic excitations and absorption spectra of molecules in solutions. This first-order PCM SAC-CI method considers the solvent effects on the energies of excited states up to the first-order with using the zeroth-order wavefunctions. This method can avoid the costly iterative procedure of the self-consistent reaction field calculations. The first-order PCM SAC-CI calculations well reproduce the results obtained by the iterative method for various types of excitations of molecules in polar and nonpolar solvents. The first-order contribution is significant for the excitation energies. The results obtained by the zeroth-order PCM SAC-CI, which considers the fixed ground-state reaction field for the excited-state calculations, are deviated from the results by the iterative method about 0.1 eV, and the zeroth-order PCM SAC-CI cannot predict even the direction of solvent shifts in n-hexane for many cases. The first-order PCM SAC-CI is applied to studying the solvatochromisms of (2,2(')-bipyridine)tetracarbonyltungsten [W(CO)4(bpy), bpy = 2,2(')-bipyridine] and bis(pentacarbonyltungsten)pyrazine [(OC)5W(pyz)W(CO)5, pyz = pyrazine]. The SAC-CI calculations reveal the detailed character of the excited states and the mechanisms of solvent shifts. The energies of metal to ligand charge transfer states are significantly sensitive to solvents. The first-order PCM SAC-CI well reproduces the observed absorption spectra of the tungsten carbonyl complexes in several solvents.

A complete assignment of the vibrational spectra of sucrose in aqueous medium based on the SQM methodology and SCRF calculations

In the present study, a complete assignment of the vibrational spectra of sucrose in aqueous medium was performed combining Pulay’s Scaled Quantum Mechanics Force Field (SQMFF) methodology with self-consistent reaction field (SCRF) calculations. Aqueous saturated solutions of sucrose and solutions at different molar concentrations of sucrose in water were completely characterized by infrared, HATR, and Raman spectroscopies. In accordance with reported data of the literature for sucrose, the theoretical structures of sucrose penta and sucrose dihydrate were also optimized in gas and aqueous solution phases by using the density functional theory (DFT) calculations. The solvent effects for the three studied species were analyzed using the solvation PCM/SMD model and, then, their corresponding solvation energies were predicted. The presence of pure water, sucrose penta-hydrate, and sucrose dihydrate was confirmed by using theoretical calculations based on the hybrid B3LYP/6-31G∗ method and the experimental vibrational spectra. The existence of both sucrose hydrate complexes in aqueous solution is evidenced in the IR and HATR spectra by means of the characteristic bands at 3388, 3337, 3132, 1648, 1375, 1241, 1163, 1141, 1001, 870, 851, 732, and 668cm−1 while in the Raman spectrum, the groups of bands in the regions 3159–3053cm−1, 2980, 2954, and 1749–1496cm−1 characterize the vibration modes of those complexes. The inter and intra-molecular H bond formations in aqueous solution were studied by Natural Bond Orbital (NBO) and Atoms in Molecules theory (AIM) investigation.

Density Functional Theory Study of the Complexation of the Uranyl Dication with Anionic Phosphate Ligands with and without Water Molecules

The structures, vibrational frequencies and energetics of anhydrous and hydrated complexes of UO2(2+) with the phosphate anions H2PO4(-), HPO4(2-), and PO4(3-) were predicted at the density functional theory (DFT) and MP2 molecular orbital theory levels as isolated gas phase species and in aqueous solution by using self-consistent reaction field (SCRF) calculations with different solvation models. The geometries and vibrational frequencies of the major binding modes for these complexes are compared to experiment where possible and good agreement is found. The uranyl moiety is nonlinear in many of the complexes, and the coordination number (CN) 5 in the equatorial plane is the predominant binding motif. The phosphates are found to bind in both monodentate and bidentate binding modes depending on the charge and the number of water molecules. The SCRF calculations were done with a variety of approaches, and different SCRF approaches were found to be optimal for different reaction types. The acidities of HxPO4(3-x) in HxPO4(3-x)(H2O)4, x = 0-3 complexes were calculated with different SCRF models and compared to experiment. Phosphate anions can displace water molecules from the first solvation shell at the uranyl exothermically. The addition of water molecules can cause the bonding of H2PO4(-) and HPO4(2-) to change from bidentate to monodentate exothermically while maintaining CN 5. The addition of water can generate monodentate structures capable of cross-linking to other uranyl phosphates to form the types of structures found in the solid state. [UO2(HPO4)(H2O)3] is predicted to be a strong base in the gas phase and in aqueous solution. It is predicted to be a much weaker acid than H3PO4 in the gas phase and in solution.

Fundamental Thermochemical Properties of Amino Acids: Gas-Phase and Aqueous Acidities and Gas-Phase Heats of Formation

The gas-phase acidities of the 20 L-amino acids have been predicted at the composite G3(MP2) level. A broad range of structures of the neutral and anion were studied to determine the lowest energy conformer. Excellent agreement is found with the available experimental gas-phase deprotonation enthalpies, and the calculated values are within experimental error. We predict that tyrosine is deprotonated at the CO(2)H site. Cysteine is predicted to be deprotonated at the SH but the proton on the CO(2)H is shared with the S(-) site. Self-consistent reaction field (SCRF) calculations with the COSMO parametrization were used to predict the pK(a)'s of the non-zwitterion form in aqueous solution. The differences in the non-zwitterion pK(a) values were used to estimate the free energy difference between the zwitterion and nonzwitterion forms in solution. The heats of formation of the neutral compounds were calculated from atomization energies and isodesmic reactions to provide the first reliable set of these values in the gas phase. Further calculations were performed on five rare amino acids to predict their heats of formation, acidities, and pK(a) values.

Density functional investigations on alkali metal (Li, Na, K) catalyzed thymidylyl (3′–5′) thymidine phosphodiester hydrolysis

Alkali metal (Li, Na or K) catalyzed phosphodiester hydrolysis in thymidylyl (3′–5′) thymidine (Tp-OT) has been analyzed employing density functional calculations. Different mechanistic pathways of hydrolysis incorporating one (‘A’ and ‘B’) or two metal ions (‘C’, ‘D’ or ‘E’) are considered. In pathways ‘A’ and ‘B’ the metal ion is bound to different oxygens of diester group. The pathway ‘C’ facilitates formation of six-membered ring wherein OH− interacts with different oxygens of phosphoryl group. On the other hand the energetic associated with pathways which incorporate two metal ions one bound to nucleophile and other interacting with either oxygen on 5′-thymidine (‘D’ pathway) or the alkali metal attached to different oxygens of phosphoryl group in Tp-OT (‘E’ pathway) were also calculated. The reactant, product, intermediate with pentavalent coordinating metal as local minima along with two transition states were identified on the potential energy surface for ‘D’ (in Li and Na) and ‘E’ pathways (for Li, Na, K). Thus, a two-step mechanism comprising of nucleophile attack as initial step followed by departure of 5′-thymidine (the leaving group) has been suggested. Self-consistent reaction field calculations reveal the activation free energies to be: Li (78.8kJmol−1)<Na (80.6kJmol−1)<K (94.8kJmol−1) in the presence water as solvent.

An experimental and theoretical study of l-tryptophan in an aqueous solution, combining two-layered ONIOM and SCRF calculations

ONIOM and SCRF calculations were performed to study the most stable theoretical structure of l-tryptophan in an aqueous solution phase and to observe the changes occurring in the structural and vibrational properties of l-tryptophan in the aqueous media. l-Tryptophan was characterized by infrared and Raman spectroscopies in the solid state and as an aqueous solution. Optimized geometries and relative stabilities for the l-tryptophan zwitterion were calculated while taking into account solvent effects using the self-consistent reaction field (SCRF) theory. The obtained results in the aqueous solution were compared with those calculated for the zwitterion in the gas phase by means of two-layered ONIOM calculations. For the complete assignments of the IR and Raman spectra of l-tryptophan in the aqueous solution phase, density functional theory (DFT) calculations were combined with Pulay's scaled quantum mechanical force field (SQMFF) methodology in order to fit the theoretical wavenumber values to the experimental values. Additionally, the roles of specific and bulk contributions from solvent effects on the properties of l-tryptophan were analyzed. Furthermore, bands corresponding to the normal modes of vibration were localized and assigned, and they served as the bases for the calculations of the corresponding force constants. Significant effects on the geometrical and vibrational frequencies were found for the studied zwitterion.

Theoretical study of 2-phenylbenzoxazole derivatives and derived phenolic Schiff compounds in gas and solution phases: Electronic structures and optical properties

Theoretical investigation has been carried out for the electronic structures, optical properties and electron transition mechanism of R-substituted 2-phenylbenzoxazole complexes ( nb) and derived phenolic Schiff bases ( na) ( n = 1, R = CH 3; n = 2, R = N(CH 3) 2; n = 3, R = Cl; n = 4, R = NO 2). In the gas phase, the ground and excited states were fully optimized at the B3LYP/cc-pVDZ, HF/cc-pVDZ and CIS/cc-pVDZ, respectively. For each derivative, two conformations are available, one with a downward hydrogen (H2) and the other with an upward hydrogen, and the former one is more stable than the latter one. Absorption and emission spectra of all species were calculated by the time-dependent density functional theory (TD-DFT) based on the ground and excited states geometries. The absorption and emission spectra were consistently blue shifted in going from na to nb. The solvent effects on molecular geometries and optical properties were characterized in several solvents from B3LYP/cc-pVDZ and HF/cc-pVDZ calculations employing the Onsager model within the framework of the self-consistent reaction field (SCRF) theory. The SCRF calculations provide reliable information regarding the solvent effects on the geometries and optical properties of the conjugate compounds.

Density functional theory analysis of structure, energetics, and spectroscopy for the Mn-Fe active site of Chlamydia trachomatis ribonucleotide reductase in four oxidation states.

Models for the Mn-Fe active site structure of ribonucleotide reductase (RNR) from pathogenic bacteria Chlamydia trachomatis (Ct) in different oxidation states have been studied in this paper, using broken-symmetry density functional theory (DFT) incorporated with the conductor like screening (COSMO) solvation model and also with finite-difference Poisson-Boltzmann self-consistent reaction field (PB-SCRF) calculations. The detailed structures for the reduced Mn(II)-Fe(II), the met Mn(III)-Fe(III), the oxidized Mn(IV)-Fe(III) and the superoxidized Mn(IV)-Fe(IV) states are predicted. The calculated properties, including geometries, (57)Fe Mossbauer isomer shifts and quadrupole splittings, and (57)Fe and (55)Mn electron nuclear double resonance (ENDOR) hyperfine coupling constants, are compared with the available experimental data. The Mössbauer and energetic calculations show that the (mu-oxo, mu-hydroxo) models better represent the structure of the Mn(IV)-Fe(III) state than the di-mu-oxo models. The predicted Mn(IV)-Fe(III) distances (2.95 and 2.98 A) in the (mu-oxo, mu-hydroxo) models are in agreement with the extended X-ray absorption fine structure (EXAFS) experimental value of 2.92 A (Younker et al. J. Am. Chem. Soc. 2008, 130, 15022-15027). The effect of the protein and solvent environment on the assignment of the Mn metal position is examined by comparing the relative energies of alternative mono-Mn(II) active site structures. It is proposed that if the Mn(II)-Fe(II) protein is prepared with prior addition of Mn(II) or with Mn(II) richer than Fe(II), Mn is likely positioned at metal site 2, which is further from Phe127.

Crystal structure, NMR and theoretical investigations on 2-( o-hydroxy-anilino)-1,4-napthoquinone

Crystal structure, 1H NMR and cyclic voltammetric investigations of 2-( o-hydroxy-anilino)-1,4-napthoquinone (HAN), resulting from coupling of aminophenol with 2-hydroxy-1,4-napthoquinone, have been carried out. X-ray structure reveals that the HAN ligand crystallizes in orthorhombic space group Pca2 1 with Z = 4, forming a chain via inter-molecular O2⋯H1A O1 and C15 H15⋯O3 interactions. Both 1H NMR and cyclic voltammetry experiments suggest the titled ligand is associated and exists as dimer in d 6-DMSO while the monomer has been predicted in CDCl 3 solution. Density functional calculations can be utilized to gauge the strength of hydrogen-bonded interactions from the 1H chemical shifts in the NMR spectra. Self-consistent reaction field (SCRF) calculations further support the inferences drawn from cyclic voltammetry experiments.

Hydrogen bonding of single acetic acid with water molecules in dilute aqueous solutions

In separation processes, hydrogen bonding has a very significant effect on the efficiency of isolation of acetic acid (HOAc) from HOAc/H2O mixtures. This intermolecular interaction on aggregates composed of a single HOAc molecule and varying numbers of H2O molecules has been examined by using ab initio molecular dynamics simulations (AIMD) and quantum chemical calculations (QCC). Thermodynamic data in aqueous solution were obtained through the self-consistent reaction field calculations and the polarizable continuum model. The aggregation free energy of the aggregates in gas phase as well as in aqueous system shows that the 6-membered ring is the most favorable structure in both states. The relative stability of the ring structures inferred from the thermodynamic properties of the QCC is consistent with the ring distributions of the AIMD simulation. The study shows that in dilute aqueous solution of HOAc the more favorable molecular interaction is the hydrogen bonding between HOAc and H2O molecules, resulting in the separation of acetic acid from the HOAc/H2O mixtures with more difficulty than usual.

DFT calculations of comparative energetics and ENDOR/Mössbauer properties for two protonation states of the iron dimer cluster of ribonucleotide reductase intermediate X.

Two models (I and II) for the active site structure of class-I ribonucleotide reductase (RNR) intermediate X in subunit R2 have been studied in this paper, using broken-symmetry density functional theory (DFT) incorporated with the conductor like screening (COSMO) solvation model and with the finite-difference Poisson-Boltzmann self-consistent reaction field (PB-SCRF) calculations. Only one of the bridging groups between the two iron centers is different between model-I and model-II. Model-I contains two mu-oxo bridges, while model-II has one bridging oxo and one bridging hydroxo. These are large active site models including up to the fourth coordination shell H-bonding residues. Mössbauer and ENDOR hyperfine property calculations show that model-I is more likely to represent the active site structure of RNR-X. However, energetically our pK(a) calculations at first highly favored the bridging oxo and hydroxo (in model-II) structure of the diiron center rather than having the di-oxo bridge (in model-I). Since the Arg236 and the nearby Lys42, which are very close to the diiron center, are on the protein surface of RNR-R2, it is highly feasible that one or two anion groups in solution would interact with the positively charged side chains of Arg236 and Lys42. The anion group(s) can be a reductant, phosphate, sulfate, nitrate, and other negatively charged groups existing in biological environments or in the buffer of the experiment. Since sulfate ions certainly exist in the buffer of the ENDOR experiment, we have examined the effect of the sulfate (SO(4)(2-), surrounded by explicit water molecules) H-bonding to the side chain of Arg236. We find that when sulfate interacts with Arg236, the carboxylate group of Asp237 tends to be protonated, and once Asp237 is protonated, the Fe(iii)Fe(iv) center in X favors the di-oxo bridge (model-I). This would explain that the ENDOR observed RNR-X active site structure is likely to be represented by model-I rather than model-II.

An efficient implementation for determining volume polarization in self-consistent reaction field theory

An efficient algorithm of the surface and volume polarization for electrostatics (SVPE) method in self-consistent reaction field (SCRF) theory, denoted by SV(1)PE, has been proposed to simulate direct volume polarization potential with a single layer of point charges outside the solute cavity while the indirect effects of volume polarization on surface polarization are still simulated with multiple layers of point charges. The free energies of solvation calculated using the SV(1)PE algorithm (implemented in GAUSSIAN03) reproduce the corresponding values calculated using the standard SVPE implementation within an error of only approximately 0.1% when the solute cavity is defined by the standard 0.001e/a(0) (3) solute charge isodensity contour. The SV(1)PE results are much less sensitive to the used cavity size in comparison with the well-established surface and simulated volume polarization for electrostatics [SS(V)PE] method which simulates volume polarization through an additional surface charge distribution on the cavity surface. The SCRF calculations using the SV(1)PE method are more efficient than those using the original SVPE method.

A Computational Investigation of the Geometrical Structure and Protodeboronation of Boroglycine, H2N−CH2−B(OH)2

In this article the geometrical structure of the simple, achiral, alpha-amino boronic acid boroglycine, H2N-CH2-B(OH)2, was investigated using density functional theory (DFT), second-order Møller-Plesset (MP2) perturbation theory, and coupled cluster methodology with single- and double-excitations (CCSD); the effects of an aqueous environment were incorporated into the results by using a few explicit water molecules and/or self-consistent reaction field (SCRF) calculations with the IEF polarizable continuum model (PCM). Neutral reaction mechanisms were investigated for the direct protodeboronation (hydrolysis) of boroglycine (H2O+H2N-CH2-B(OH)2-->B(OH)3+H2N-CH3), for which DeltaH degrees 298 was -21.9 kcal/mol at the MP2(FC)/aug-cc-pVDZ level, and for the 1,2-carbon-to-nitrogen shift of the -B(OH)2 moiety (H2N-CH2-B(OH)2-->H3C-NH-B(OH)2), for which the corresponding value of DeltaH degrees 298 was -18.2 kcal/mol. A boron-oxygen double-bonded intermediate was found to play an important role in the 1,2-rearrangement mechanism.

Computational study on the conversion of an aziridine and iminium salt to a 1,2-diamine

DFT calculations employing the SCRF-B3LYP/6-311+G(d) level of theory have been employed in order to quantitatively characterize the mechanism of the ring-opening reaction of (s)-1-benzyl-2-methyl-aziridine and an iminium salt to a 1,2-diamine, in the presence of lithium iodide. Computational results indicate that the optimal reaction pathway may proceed via an aziridinium cation intermediate mechanism, rather than by an S N2 mechanism. Self-consistent reaction field (SCRF) calculations, using the PCM model and THF as solvent, showed an energetic barrier for aziridine ring-opening to be on the order of ∼10.9 kcal/mol; indicating the process to be thermodynamically spontaneous. The catalytic role of I − and substituent effects are also elaborated upon herein.