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Methyl transfer reactions mediated by cobalamins (Cbls) have been considered as one of the most important biologically relevant molecular transformations for many enzymatic reactions catalyzed by Cbl-dependent enzymes. The exact mechanism of methyl transfer reactions involving Cbls is still poorly understood. To investigate the mechanistic details of Cbl mediated methylations by alkyl halides, density functional theory (DFT) along with the polarizable continuum model (PCM/water) for solvation has been applied. Two different mechanisms have been examined, namely S N 2 and radical-based electron transfer (ET) to elucidate the methyl transfer reaction. The calculations have suggested that the methyl transfer from methyl halides proceeds through S N 2 nucleophilic displacement. However, with more bulky alkyl substrate, namely isopropyl and tert-butyl halides the reaction followed the ET-based radical pathway which is associated with an ET from diradical form of cob(I)alamin to alkyl halides. Our proposed mechanism for alkyl transfer reaction corroborates with the experimental findings, which reported a mechanistic switch from a two-electron (S N 2-type) to a one-electron mechanism for sterically demanding alkyl halides. The present theoretical contribution provides more in-depth insight into the methyl transfer reaction catalyzed by corrinoid-dependent methyltransferases.

Antivitamins B12 represent an important class of vitamin B12 analogues that have gained recent interest in several research areas. In particular, 4-ethylphenylcobalamin (EtPhCbl) and phenylethynylcobalamin (PhEtyCbl) exemplify two such antivitamins B12 which have been characterized structurally and chemically. From a spectroscopic point of view, EtPhCbl is photolabile with a very low quantum yield of photoproducts, while PhEtyCbl is incredibly photostable. Herein, DFT and TD-DFT computations are provided to explore the photolytic properties of these compounds to shed light on the electronic properties that are indicative of these differences. Potential energy surfaces (PESs) were constructed to investigate the mechanisms of photodissociation leading to radical pair (RP) formation and the mechanisms of deactivation to the ground state. The S1 PESs for each antimetabolite contain two energy minima, one being the metal-to-ligand charge transfer (MLCT) and another the ligand-field (LF) state. There are two po...

Cobalamins are ubiquitous cobalt-based corrinoid cofactors of various transferases, exemplified by methyltransferases and adenosyltransferases. The cobalt oxidation state in these cobalamins directly influences their coordination environment and the redox properties. Cobalt ion in these cobalamins prominently exist in three oxidation states (I, II and III). The main focus of this review is the lowest cobalt oxidation state, cob(I)alamin. Cob(I)alamin, also referred to as “supernucleophile”, has broad reactivity properties. This review focuses on how recent advances in computational chemistry have contributed towards improving our understanding of the coordination environment, electronic structure, spectroscopic properties of cob(I)alamin and its implications for the catalytic functioning of methyltransferases. Density functional theory and quantum mechanics/molecular mechanics approaches provide new insights into the coordination environment of cob(I)alamin bound inside methyltransferase and the molecular mechanism of methyl transfer to cob(I)alamin. In addition, the wavefunction-based multireference approach has revealed the details of the ground state electronic structure and electronically excited S 1 state of cob(I)alamin.

Biologically active forms of cobalamins are crucial cofactors in biochemical reactions and these metabolites can be inhibited by their structurally similar analogues known as antivitamins B12. Phenylethynylcobalamin (PhEtyCbl) or 4-ethylphenylcobalamin (EtPhCbl) exemplify recently synthesized and structurally characterized antivitamins B12. Herein, DFT and TD-DFT studies of EtPhCbl are provided to explore its photochemical behavior, which may lead to design of arylcobalamins that can be used as therapeutic agents in light activated drug applications. To understand the photolability of EtPhCbl, a potential energy surface (PES) for the photodissociation of the Co–C bond was constructed. The S1 PES contains two energy minima, one being metal-to-ligand charge transfer (MLCT) and another the ligand-field (LF) state. There are two possible pathways for photodissociation: the first pathway (path A) involves initially lengthening the Co–C bond from the MLCT minimum and then elongation of Co–NIm while the second pathway (path B) involves the lengthening of the Co–NIm bond through the MLCT region followed by the lengthening of the Co–C bond through the LF region. It is shown that photodissociation involving path A is not energetically favorable whereas preferable photodissociation of the Co–C bond involves path B.

Vitamin B

The nature of electronically excited states of the super-reduced form of vitamin B(12) (i.e., cob(I)alamin or B(12s)), a ubiquitous B(12) intermediate, was investigated by performing quantum-chemical calculations within the time-dependent density functional theory (TD-DFT) framework and by establishing their correspondence to experimental data. Using response theory, the electronic absorption (Abs), circular dichroism (CD) and magnetic CD (MCD) spectra of cob(I)alamin were simulated and directly compared with experiment. Several issues have been taken into considerations while performing the TD-DFT calculations, such as strong dependence on the applied exchange-correlation (XC) functional or structural simplification imposed on the cob(I)alamin. In addition, the low-lying transitions were also validated by performing CASSCF/MC-XQDPT2 calculations. By comparing computational results with existing experimental data a new level of understanding of electronic excitations has been established at the molecular level. The present study extends and confirms conclusions reached for other cobalamins. In particular, the better performance of the BP86 functional, rather than hybrid-type, was observed in terms of the excitations associated with both Co d and corrin π localized transitions. In addition, the lowest energy band was associated with multiple metal-to-ligand charge transfer excitations as opposed to the commonly assumed view of a single π → π* transition followed by vibrational progression. Finally, the use of the full cob(I)alamin structure, instead of simplified molecular models, shed new light on the spectral analyses of cobalamin systems and revealed new challenges of this approach related to long-range charge transfer excitations involving side chains.

Time-dependent density functional theory (TD-DFT) has been applied to investigate the relevant excited states involved in the photodissociation of hydroxocobalamin (HOCbl). The TD-DFT/BP86/6-31G(d) and TD-DFT/BP86/6-311G(d,p)//BP86-631G(d) calculations suggest that the photoscission of Co–OH bond is mediated by the repulsive 1(n + dCo → σ∗Co–OH) singlet state that drops in energy along the reaction stretch coordinate and yields the products of photodissociation i.e., Cob(II)alamin and hydroxyl radical. The channel involving the repulsive triplet state may also be a possible mechanistic pathway. The present calculations thus may help in enhancing our understanding about the photophysical behavior of HOCbl which has implications in the investigation of biological complexes such as DNA and RNA.

Density functional theory using a variety of functionals (i.e., BP86, B3LYP, B3LYP-D, B3PW91, PBE1PBE, mPW1PBE, mPW3PBE, and mPW1PW91) in combination with a polarizable continuum solvent model is applied to compute the standard reduction potentials of methylcobalamin (MeCbl) and adenosylcobalamin (AdoCbl) cofactors, respectively. A fairly good agreement between experiment and theory is obtained when the reduction potentials are computed in dimethylforamide solvent using BP86/6-31+G* level of theory. The computed reduction potentials of MeCbl and AdoCbl cofactors are predicted within 0.1–0.2 V of their experimental values. The reliability of the calibrated protocol is further testified when an acceptable degree of reproducibility (experiment vs. theory) is achieved with regard to the reduction potential of the cob(II)alamin/cob(I)alamin couple. The calibrated theoretical strategy is then exploited to understand the role of the upper axial ligand in governing the reduction potentials of alkylcobalamins. It is noted that the electron donating axial ligands tend to depress the reduction potential while electron withdrawing axial ligands (fluorinated ligands) raise the reduction potentials of the alkylcobalamins. The electronic structure calculations imply that the computed reduction potentials of alkylcobalamins are directly correlated with the energies of their lowest unoccupied molecular orbitals (ELUMO values). Thus it is concluded that the ELUMO values of alkylcobalamins that depend upon the electronic nature of the upper axial ligands serve as the key descriptors of their reduction potentials. © 2012 Wiley Periodicals, Inc.

Quantum chemical computations are used to study the electronic and structural properties of the cob(I)alamin intermediate of the cobalamin-dependent methionine synthase (MetH). QM(DFT)/MM calculations on the methylcobalamin (MeCbl) binding domain of MetH reveal that the transfer of the methyl group to the substrate is associated with the displacement of the histidine axial base (His759). The axial base oscillates between a His-on form in the Me-cob(III)lamin:MetH resting state, where the Co-N(His759) distance is 2.27 A, and a His-off form in the cob(I)alamin:MetH intermediate (2.78 A). Furthermore, QM/MM and gas phase DFT calculations based on an unrestricted formalism show that the cob(I)alamin intermediate exhibits a complex electronic structure, intermediate between the Co(I) and Co(II)-radical corrin states. To understand this complexity, the electronic structure of Im···[Cob(I)alamin] is investigated using multireference CASSCF/QDPT2 calculations on gas phase models where the axial histidine is modeled by imidazole (Im). It is found that the correlated ground state wave function consists of a closed-shell Co(I) (d(8)) configuration and a diradical contribution, which can be described as a Co(II) (d(7))-radical corrin (π*)(1) configuration. Moreover, the contribution of these two configurations depends on the Co-NIm distance. At short Co-NIm distances (

Density functional theory has been applied to a series of unsubstituted planar metalloporphyrins (MPs) to elucidate how geometry and frequencies correlate with the metal-nitrogen distance, referred to as the core size. Different transition metals can invoke expansion or contraction of the porphyrin core due to electronic effects resulting from the amount of d-electron pairing as well as occupancy of the d(x(2)(-y(2))) orbital. A full vibrational analysis consisting of all in-plane and out-of-plane frequencies was carried out, and the resulting modes were plotted against core size for a linear analysis and grouped within symmetry blocks. The modes were separated according to planarity, and all modes with a large slope and best fit greater than 0.8 were considered sensitive to metal-nitrogen distances. All planar skeletal modes above 1450 cm(-1), including the pyrolle ring deformations, are found to be core-size sensitive. The most significant out-of-plane modes sensitive to core size are gamma(8) and gamma(9), which are infrared active and grouped within the A(2u) symmetry block. The present work also opens possible quantitative applications for the correlation of spectroscopic properties of MPs and heme proteins with actual structural parameters.

Relativistic density functional theory (DFT) has been applied to explore electron paramagnetic resonance (EPR) parameters as well as ground-state spin properties of cob(II)alamin. Cob(II)alamin is an intermediate which participates in many reactions catalyzed by derivatives of vitamin B12 and that can be detected by EPR spectroscopy due to the presence of the paramagnetic Co(II)(d(7)) center. The full structure of cob(II)alamin and its truncated analogues were examined. Three different DFT functionals, B3LYP, BP86, and PBE, have been applied to obtain the g- and A-tensors. Both tensors are axially symmetric and can provide useful insight into specific axial ligand interactions. Of the functionals tested, the hybrid B3LYP functional, was found to overestimate the axial bond length, whereas the GGA-type functionals, BP86 and PBE, produced geometries consistent with experimental data. The reliability of nonrelativistic and approximate relativistic methods for the calculation of EPR parameters has also been tested against a fully relativistic four-component approach. Since the EPR parameters are very sensitive to the local environment surrounding Co(II), a theoretical (DFT-BP86) estimate of the dependence of the g- and A-tensors on the metal-to-axial ligand interatomic distance can be directly correlated with EPR measurements. The usefulness of such an approach has been demonstrated for the methionine synthase enzyme where the reduction of cob(II)alamin takes place during the reactivation cycle.

Density functional theory (DFT)-based normal mode calculations have been carried out on models for B12-cofactors to assign reported isotope-edited resonance Raman spectra, which isolate vibrations of the organo–Co group. Interpretation is straightforward for alkyl–Co derivatives, which display prominent Co–C stretching vibrational bands. DFT correctly reproduces Co–C distances and frequencies for the methyl and ethyl derivatives. However, spectra are complex for adenosyl derivatives, due to mixing of Co–C stretching with a ribose deformation coordinate and to activation of modes involving Co–C–C bending and Co–adenosyl torsion. Despite this complexity, the computed spectra provide a satisfactory re-assignment of the experimental data. Reported trends in adenosyl–cobalamin spectra upon binding to the methylmalonyl CoA mutase enzyme, as well as on subsequent binding of substrates and inhibitors, provide support for an activation mechanism involving substrate-induced deformation of the adenosyl ligand.

Computational modeling of the enzymatic activity of B12-dependent enzymes requires a detailed understanding of the factors that influence the strength of the CoC bond and the limits associated with a particular level of theory. To address this issue, a systematic analysis of the electronic and structural properties of coenzyme B12 models has been performed to establish the performance of three different functionals including B3LYP, BP86, and revPBE. In particular the cobalt–carbon bond dissociation energies, axial bond lengths, and selected stretching frequencies have been analyzed in detail. Current analysis shows that widely used B3LYP functional significantly underestimates the strength of the CoC bond while the nonhybrid BP86 functional produces very consistent results in comparison to experimental data. To explain such different performance of these functionals molecular orbital analysis associated with axial bonds has been performed to show differences in axial bonding provided by hybrid and nonhybrid functionals. © 2006 Wiley Periodicals, Inc. J Comput Chem 27: 1429–1437, 2006

This work represents the first theoretical attempt to assign vibrational modes for methylcobalamin (MeCbl), the biologically active form of a vitamin B12 derivative. Full vibrational analysis of Me...

Recent progress in computational modeling of the catalytic activation of cobalt-carbon bond cleavage shows that quantum chemical calculations could be an important part of coenzyme B(12) research. Particular emphasis has been placed on density functional theory, which is now emerging as a powerful tool to elucidate the electronic structure and spectroscopic properties of the active sites of metalloenzymes.

We present a comprehensive analysis of the geometric and electronic properties of the metal coordination center domain of the iron(II) complex of the antitumor drug bleomycin (BLM) using density functional theory (DFT). The various experimental studies devoted to establishing the nature of the metal coordination center in BLM suggest that the metal is five-coordinated, with a sixth site available for exogenous ligand binding. Among the five ligands, four of them form an equatorial coordination sphere, but the nature of the fifth axial ligand remains controversial. To elucidate the nature of the metal coordination center in Fe(II) -BLM, six structurally different conformers resembling the active site have been investigated using DFT. An optimal geometry has been found for each conformer in the singlet, triplet, and quintet electronic states. The electronic ground state was identified as a four-coordinate species with intermediate spin state. However, when the results of these calculations were compared with the latest 2D NMR data, the best agreement was found between the five-coordinated theoretical model and experiment. Stereoelectronic analysis of four-coordinate conformers has shown that the Fe out-of-plane displacement controls the spin state. The high-spin state potential energy surface intersects the triplet state potential energy surface along the doming-mode coordinate when the iron atom is displaced about 0.4 A from the equatorial nitrogens average plane. This intersection is the result of different iron d orbital occupancy in quintet and triplet electronic states.

This Letter introduces a systematic development of a quantitative vibrational force field (FF) capable of modeling vibrational spectra of cobalt corrinoids (B 12 derivatives). The scaled quantum mechanical (SQM) method is used to refine density functional theory (DFT) based force constants calculated at the B3LYP level of theory. The reliability of the DFT–SQM FF for cobalt corrinoids is tested on a six-coordinate methylcobalamin Im–[Co III –corrin]–CH 3 model. It is shown that the computed frequencies and Raman intensities permit detailed vibrational assignment. This analysis illustrates the utility of DFT–SQM FF in making detailed connections between the structure of cobalt corrinoids and their vibrational spectra.

The results of the DFT (B3LYP) calculations of the structures and force fields of the five spin states of a model deoxyheme (Cs symmetry) are presented. It is shown that axial binding of imidazole ...

Vibrational spectra of CO, NO, and O2 adducts of heme proteins contain information on interactions of the heme and its bound ligands with the surrounding protein matrix that may help in elucidating the mechanism of small-molecule activation. Whereas the heme−CO system is well studied and a framework exists for the interpretation of such interactions, heme−NO and −O2 complexes have not been systematically investigated. Here we examine resonance Raman spectra of all three classes of adducts, combining literature values with new data for FeIINO porphyrins having both electron-donating and electron-withdrawing substituents. Negative linear correlations are observed for all three adducts between their Fe−XO and X−O stretching frequencies. The slopes of these correlation lines are −0.4 for five-coordinate FeCO and FeNO porphyrins and −0.8 for five-coordinate FeO2 adducts. Thus, Fe−NO and Fe−O2 bonds are equally or even more sensitive than Fe−CO bonds to electronic influences that affect metal-to-ligand π back-b...

The gauge including atomic orbital (GIAO) method at the self-consistent field (SCF) level of theory was used to calculate magnetic shielding tensors in free base porphyrin (H2P) and in magnesium (MgP) and zinc (ZnP) metalloporphyrins, as well as in the MgP(H2O) and MgP(H2O)2 complexes. All principal components of the calculated shielding tensors are reported. We have recorded new solution NMR spectra for all three molecules under identical conditions, to ensure the reliability of small differences in their NMR shifts. The calculated isotropic values are compared with these values and with low-temperature solid-state shifts, which resolve the tautomerism in H2P. Agreement with experiment is good. It is encouraging that the calculations correctly reproduce most of the the small differences in the chemical shifts. A comparison of the observed and calculated NMR shifts of MgP leads to the conclusion that the species observed in tetrahydrofuran solution is either MgP(H2O)2 or MgP(THF)2. We have calculated the ...

The full configuration interaction method in the space of fractionally occupied unrestricted natural orbitals (UNO-CAS method) is extended to excited states as well as to strongly correlated and reactive systems with large active spaces. This is accomplished by␣using restricted active space (RAS) wave functions introduced by Olsen et al. [(1988) J Chem Phys 89: 2185] and using the UNOs without the expensive orbital optimization step. In RAS, the space of active orbitals is subdivided into three groups: a group with essentially doubly occupied orbitals (RAS1), the usual CAS space (RAS2), and a space with weakly occupied active orbitals (RAS3). We select these spaces on the basis of the occupation numbers of the UNOs. All possible electron distributions are allowed in the usual CAS space, but the number of vacancies is limited in RAS1 and the number of electrons is limited in RAS3. We discuss an efficient algorithm for generating a RAS wave function. This is based on the Handy-Knowles determinantal expansion with an addressing scheme adopted for the restricted expansion. Results for both ground and excited states of azulene and free base porphyrin are presented.

Following on from previous work on free-base porphyrin, we present the results of a comprehensive study on the structure and inner-hydrogen migration in porphycene, a structural isomer of porphyrin. We used density functional theory with the hybrid B3-LYP exchange-correlation functional, and both the 6-31G(d) and a triple-zeta double-polarization (TZ2P) basis set (the latter containing 726 contracted basis functions). Full geometry optimizations were carried out and all stationary points were characterized by vibrational analysis. A scaled quantum mechanical (SQM) treatment of the theoretical force constants shows convincingly that the trans-isomer is the ground state, with trans–trans inner-hydrogen migration taking place—as is the case with porphyrin—in a two-step process via a (highly unstable) cis intermediate. With the TZ2P basis, excluding zero-point effects, the trans–cis barrier height is 4.9 kcal/mol, the cis–trans energy difference is 2.4 kcal/mol and the reverse cis–trans barrier height is only...

The recent development of density functional theory (DFT) makes it possible to calculate accurately metalloporphyrin structures and potential surfaces. This is illustrated for nickel porphine, the vibrations of which are reliably assigned from extensive spectroscopic studies. With a minimal set of scaling factors, the DFT force field reproduces the experimental wavenumbers to higher accuracy than the best available empirical force field. Moreover, the calculated intensities are in good accord with experiment, including the surprisingly large off-resonant Raman intensities of non-totally symmetric (B1g) modes. DFT also predicts a slight ruffling distortion of the porphyrin, and accurately reproduces the IR intensity of a distortion-induced out-of-plane mode. In the case of iron porphine, DFT correctly predicts an intermediate-spin (3A2g) ground state, with short Fe—N bonds, and a high-spin (5A1g) excited state with a planar geometry but an expanded porphyrin core. When the Fe is displaced from the plane, the potential rises faster for the 3A2g than the 5A1g state, which becomes the ground state beyond a 0.4 A displacement. The doming mode is predicted to be at 71 cm-1, close to the 75 cm-1 wavenumber determined from coherent reaction dynamics in myoglobin. The vibrational wavenumbers of CO bound to heme are correctly calculated, and the potential for distorting the CO away from the heme normal is found to be surprisingly soft. Also, the transition dipole for the CO stretching mode is calculated to lag significantly behind the CO bond vector, thereby resolving an apparent discrepancy between crystallography and polarized IR spectroscopy with regard to the CO geometry in its adduct with myoglobin. Finally, the DFT force field was used successfully in conjunction with INDO calculations of the excited states, to reproduce resonance Raman intensities for NiP, both for Soret and Q-band resonances. These results give promise for developing a quantitative modeling capability for heme protein vibrational spectra. Copyright © 1998 John Wiley & Sons, Ltd.

Coenzyme B12 (AdoCbl) is one of the most biologically active forms of vitamin B12, and continues to be a topic of active research interest. The mechanism of Co-C bond cleavage in AdoCbl, and the corresponding enzymatic reactions are however, not well understood at the molecular level. In this work, time-dependent density functional theory (TD-DFT) has been applied to investigate the photodissociation of coenzyme B12. To reduce computational cost, while retaining the major spectroscopic features of AdoCbl, a truncated model based on ribosylcobalamin (RibCbl) was used to simulate Co-C photodissociation. Equilibrium geometries of RibCbl were obtained by optimization at the DFT/BP86/TZVP level of theory, and low-lying excited states were calculated by TD-DFT using the same functional and basis set. The calculated singlet states, and absorption spectra were simulated in both the gas phase, and water, using the polarizable continuum model (PCM). Both spectra were in reasonable agreement with experimental data, and potential energy curves based on vertical excitations were plotted to explore the nature of Co-C bond dissociation. It was found that a repulsive (3)(σCo-C → σ(*) Co-C) triplet state became dissociative at large Co-C bond distance, similar to a previous observation for methylcobalamin (MeCbl). Furthermore, potential energy surfaces (PESs) obtained as a function of both Co-CRib and Co-NIm distances, identify the S1 state as a key intermediate generated during photoexcitation of RibCbl, attributed to a mixture of a metal-to-ligand charge transfer (MLCT) and a σ bonding-ligand charge transfer (SBLCT) states.

We present the results of a comprehensive study on the inner-hydrogen migration in free base porphyrin, using density functional theory with the hybrid B3-LYP exchange-correlation functional, and both the 6-31G(d ) and a triple-zeta double-polarization (TZ2P) basis set. The latter computations, involving 726 contracted functions, are the largest calculations on this system to date. Full geometry optimization was carried out for the cis and trans minima, the transition state for trans-cis isomerization, and the symmetric stationary point for the synchronous trans-trans isomerization. All stationary points were characterized by vibrational analysis. Our results strongly support the conclusion, reached by earlier workers, that trans-trans hydrogen transfer occurs in a two-step process via a cis intermediate. With the TZ2P basis and including zero-point effects for the -h 2 isotopomer, the trans-cis barrier height is 13.1 kcal/mol, the cis-trans energy difference is 8.1 kcal/mol and the reverse cis-trans barrier height is 5.0 kcal/mol. The trans-cis barrier height agrees well with the value of Braun et al. (J Am Chem Soc (1996) 118: 7231) obtained from NMR line shapes and a modified Bell tunneling model, but our cis-trans energy difference is higher, and the reverse barrier is lower, than the values of Braun et al. Tunneling precludes the existence of -h 2 cis-porphyrin as an observable species, but the -d 2 and, especially, -t 2 isotopomers might be observable at low temperatures if the reverse barrier is higher than our calculated value. We predict the theoretical vibrational spectrum of cis-porphyrin and suggest that IR active modes at 566 cm−1 and 2333 cm−1 in the -d 2 isotopomer may be used to detect the presence of the cis intermediate.

The ground state geometries, scaled quantum mechanical (SQM) quadratic force fields, and infrared and Raman intensities of magnesium and zinc porphyrins (MgP and ZnP), and of (H 2 O) 2 MgP have been determined from density functional theory, using the Becke-Lee-Yang-Parr composite exchange-correlation functional (B3-LYP)_and the 6-31G ∗ basis set. The geometry of (H 2 O)MgP has also been determined. The calculated force fields have been transformed to non-redundant natural internal coordinates and scaled by six scaling factors optimized earlier for free base porphyrin. Infrared and normal Raman spectra (the latter excited with 1064 nm infrared radiation) of the title compounds have been recorded. The calculated spectra compare excellently with the experimental ones, showing the accuracy of the SQM force field, and enabling a complete assignment of the fundamentals. According to the calculations, both MgP and ZnP are planar. The Mg ion in (H 2 O)MgP is about 0.28 A out of the N 4 plane. The calculations give reliable estimates for the force constants associated with the inactive vibrations. Some of these, e.g. the ruffling of the porphyrin ring, are important and are difficult to determine experimentally.

A form of open shell perturbation theory that is invariant with respect to orbital degeneracy is proposed. This new methodology is based entirely on the spin-restricted formalism. Preliminary numerical results are presented and compared with other formulations of perturbation theory.

A modified form of multi-reference second-order perturbation theory is considered. The nature of the poor convergence of Moller-Plesset perturbation theory for systems like cyano radical or He+2, He2+2, O2+2 cations is analysed. Additionally, isomerization of the formaldehyde radical cation and the electronic ground state of ozone are considered in detail. To all of the above cases, a modified form of multi-reference second-order perturbation theory is applied and results re-examined.

Density functional theory has been applied to study the origin of the inverse and normal trans influence in alkylcobalamins. In order to cover the X-ray structural data available for alkylcobalamins with a variety of axial substituents, geometries of 28 related corrin-containing models have been optimized and analyzed. The BP86/6-31G(d) level of theory was applied which showed good reliability in reproducing the axial bond lengths. Comparison of experimental and calculated data allowed to conclude that the inverse trans influence is not a general feature of cobalamins, as it appeared from the experimental data analysis alone. Inverse trans influence is observed for the series of R groups with increasing bulk and electron donating ability. For the series of R groups having similar medium bulk, but differing significantly in the electron donating ability, normal trans influence was found. Finally, it was determined, that the axial bond lengths correlate well but differently in the two series of R groups with the orbital energies of the six molecular orbitals essential in axial interligand bonding.

A method for analyzing the A(1u)/A(2u) contents of metalloporphyrin pi-cation radicals is developed and applied to a series of unsubstituted planar metalloporphines (MPs) (M=Cr, Mn, Fe, Co, Ni, Cu, and Zn). The structures and electronic properties of the MPs and their cation radicals were calculated by density functional theory (DFT) and subsequently analyzed. It was found that the MPs with small core sizes have a tendency to form A(1u)-type radicals, while the MPs with large core size have a preference for an A(2u)-type. Neither of these pure-state species, however, is stable under the D(4)(h) symmetry, and both radical cation types are subject to pseudo-Jahn-Teller (pJT) distortion. The pJT distortion leads to structures with lower symmetry and states that have mixed character with respect to the A(1u) and A(2u) components. The degree of mixing could be estimated by employing orbital projection technique or a complementary spin density decomposition. Both techniques produce very similar results, pointing out that the frontier orbital, which becomes empty upon electron removal, plays a critical role in determining electronic properties.

Raman, ultraviolet resonance Raman (UVRR) and far-IR spectra are reported for the mercury-cysteamine complex, Hg(SCH(2)CH(2)NH(2))(2). Band assignments are made for Hg(SCH(2)CH(2)NH(2))(2), and also for [Hg(SBu(t))(3)](-) and [Hg(SMe)(3)](-) on the basis of ab initio calculations with the effective core potential approximation and also on the basis of comparison with vibrational data of corresponding thiols. The calculations show that geometry-optimized [Hg(SBu(t))(3)](-) and [Hg(SMe)(3)](-) have virtually the same Hg-S bond lengths, but very different nu(s) HgS frequencies, 196 and 268 cm(-)(1), in good agreement with the experimental data. The exceptionally low HgS frequency for [Hg(SBu(t))(3)](-) compared to [Hg(SMe)(3)](-) and to the Hg-MerR protein results from kinematic interactions of the Hg-S stretching and S-C-C bending coordinates when all three substituents at C(alpha) are carbon atoms. For Hg(SCH(2)CH(2)NH(2))(2), the HgS stretching coordinate is distributed over three modes, at 339, 273, and 217 cm(-)(1), all of which exhibit UVRR enhancement. The other contributors to these modes are angle bending and torsional coordinates of the chelate rings. Involvement of the CCN bending coordinates is supported by observed and calculated frequency shifts in D(2)O. The excitation profiles track the main UV absorption band, associated with S--Hg charge transfer. Enhancement is attributable to the weakening of the Hg-S bonds in the excited state, and probably to changes in the SCC bond angle. Also enhanced, albeit weakly, is the nu(CS) mode at 658 cm(-)(1), reflecting C-S bond shortening in the excited state. The mingling of metal-sulfur and internal ligand coordinates is reminiscent of the mingling seen in RR spectra of type 1 Cu proteins. In both cases the phenomenon may be associated with elevated torsional contributions associated with the rigidity of the ligands.