High-level ab initio calculations on the energetics of low-lying spin states of biologically relevant transition metal complexes: a first progress report

Although DFT is the unrivaled method of choice for quantum chemical studies of bioinorganic problems, little is known about its ability to predict the energetics of the low-lying electronic states of transition metal complexes. The first high-level ab initio calculations aimed at calibrating DFT vis-a-vis this issue indicate that, despite its many successes, DFT is far from infallible. In the short term, additional calibration of DFT against more elaborate ab initio methods remains an important goal for computational bioinorganic researchers. In the longer term, we are optimistic that high-level ab initio methods such as CASPT2 and CCSD(T) will be regularly used to study realistic molecules of genuine biochemical interest.     

Theoretical study of the excited states of the photosynthetic reaction center in photosystem II: electronic structure, interactions, and their origin

The excited states of the chlorophyll 6-mer in the photosystem II (PSII) reaction center (RC) were investigated theoretically using ab initio quantum chemical calculations, and the results are compared with those of the bacterial reaction center (bRC). A significant difference in the peak at the lowest energy in the absorption spectra arises from the structural asymmetry of the special pair (SP). The origin can be traced back to the structural difference in the CD helix. The low-lying excited states are characterized as a linear combination of the excited states of the chlorophyll monomers, which verifies the applicability of exciton theory. Analysis of the molecular interactions clearly explains the cause of the constructive/destructive interferences in the state transition moment. The protein electrostatic potential (ESP) decreases the energy of the charge-transfer (Chl(D1)→Pheo(D1)) state. The ESP also localizes the HOMO distribution to the P(D1) moiety and increases the ionization potential.     

An energetic correlation of ab initio and NMR studies of the 3'-gauche effect in 3'-substituted thymidines

A straightforward correlation of our experimental NMR findings on 3'-substituted thymidine derivatives with that of the ab initio calculations shows that (i) the delta Go298kNRM of N reversible S equilibrium in nucleoside can be predicted from the ab initio calculated delta ES-N obtained from 6-311++G** level of theory; (ii) the substituent-dependent steric and stereoelectronic effects on the bias of the two-state N reversible S equilibrium in nucleosides can also be predicted from the ab initio calculations with sufficiently large basis functions, and (iii) the necessity of mimicking the solvation behaviour of the experimental NMR measurement condition in the ab initio calculations of biomolecules is also emphasized.     

The axial ligand effect of oxo-iron porphyrin catalysts. How does chloride compare to thiolate?

We have performed density functional theory calculations on an oxo-iron porphyrin catalyst with chloride as an axial ligand and tested its reactivity toward propene. The reactions proceed via multistate reactivity on competing doublet and quartet spin surfaces. Close-lying epoxidation and hydroxylation mechanisms are identified, whereby in the gas phase the epoxidation reaction is dominant, while in environments with a large dielectric constant the hydroxylation pathways become competitive. By contrast to reactions with thiolate as an axial ligand all low-lying pathways have small ring-closure and rebound barriers, so it is expected that side products and rearrangements will be unlikely with Fe=O(porphyrin)Cl, whereas with Fe=O(porphyrin)SH some side products were predicted. The major differences in the electronic configurations of Fe=O(porphyrin)Cl and Fe=O(porphyrin)SH are due to strong mixing of thiolate orbitals with iron 3d orbitals, a mixing which is much less with chloride as an axial ligand. Predictions of the reactivity of ethylbenzene-h ₁₂ versus ethylbenzene-d ₁₂ are made. Electronic Supplementary Material Supplementary material is available for this article at and is accessible for authorized users.     

Coherent singlet-triplet transitions at the initial step of tubulin assembly into microtubules

Quantum chemistry calculations [DFT-B3LYP QM/MM method, 6-31G** basis set, + ab initio molecular dynamics] were used to study the action of Mg2+ on tubulin properties. It was shown that the hydration of the guanosine triphosphate-tubulin forms a protein zone structure, which includes a electron-occupied zone and a conductivity zone. The binding of Mg2+ to guanosine triphosphate-tubulin results in the unpairing of electrons in the occupied zone (triplet state formation) followed by their transition to the conductivity zone in which the inversion of spin occurs (singlet state formation). The formation of triplet state is the initial step in the subsequent protein dynamics in the picosecond range of time. The dynamics shows up as a coherent oscillating transition of tubulin between the triplet and singlet states, which is evidence of a simultaneous adjustment between nuclear and electron configurations of the protein (ab initio molecular dynamics calculations). The barrier between the triplet and singlet states does not exceed 0.60 kcal x mol(-1). The barrier overcome is considered as electron tunneling through the Fermi surface, which separates the occupied and conductivity zones. Zone formation occurs in the presence of the shell of biological water surrounding the protein.     

Theoretical study of noncovalent interactions in XCN···YO<Subscript>2</Subscript>H (X = F,Cl, Br,I; Y = P,As, Sb) complexes

Noncovalent interactions in XCN···YO₂H (X = F, Cl, Br, I; Y = P, As, Sb) complexes were investigated using ab initio calculations at the MP2/aug-cc-pVDZ level of theory. There are four different configurations of these complexes, and the complexes are formed via hydrogen bonds, halogen bonds, π-hole interactions, or dual interactions. An examination of binding distances and interaction energies suggested that π-hole bonds are more stable than the other interactions. Molecular electrostatic potentials, electron densities, second-order stabilization energies, and electron density differences were computed to study the character of these interactions.     

Ab initio calculations of electron distributions in heme-CO models

We have, by the use of ab initio calculations, found a back-bonding state of pi symmetry close to the Fermi level for CO bound to FeN5C14. We thus find it likely that small shifts of the redox potential magnitude of EF - EV magnitude of will cause relatively large changes of the CO vibrational frequency. The separation of Fe 3d orbitals in our heme model is found to agree with what is predicted by ligand field theory for Oh symmetry. This paper presents nonrelativistic Hartree-Fock-Slater calculations of the 5 sigma bonding and 2 pi back-bonding between CO and Fe. The effects of up to 19 additional atoms are discussed for models of heme (COFe to COFeN5C14). The filled back-bonding state is found to be strongly influenced by second nearest neighbor atoms. By use of symmetry orbitals we have resolved the Fe 3d orbitals into the T2g and Eg representations of the Oh point group and find the former states to be occupied whereas the latter are unoccupied. The difference in occupancy is reduced when the CO ligand is removed which also causes an increased density of states at the Fermi level, i.e., the highest occupied and lowest unoccupied orbitals. Possible correlations between our data and experimental results are discussed for heme proteins as well as for metal surfaces.     

Theoretical spectroscopy of model-nonheme [Fe(IV)OL5]2+ complexes in their lowest triplet and quintet states using multireference ab initio and density functional theory methods

The structure, energies and spectroscopic properties of a simple [FeO(NH(3))(5)](2+) model with ground states (3)A(2g) and (5)A(1g) (in approximate C(4v) symmetry) have been studied in some detail using density functional (DFT) and simplified correlated multireference ab initio methods. The results reveal similarities as well as some pronounced differences in the properties of the molecule in the two alternative spin states.     

Role of spin state on the geometry and nuclear quadrupole resonance parameters in hemin complex

Theoretical calculations of structural parameters, 57Fe, 14N and 17 O electric field gradient (EFG) tensors for full size-hemin group have been carried out using density functional theory. These calculations are intended to shed light on the difference between the geometry parameters, nuclear quadrupole coupling constants (QCC), and asymmetry parameters (eta Q) found in three spin states of hemin; doublet, quartet and sextet. The optimization results reveal a significant change for propionic groups and porphyrin plane in different spin states. It is found that all principal components of EFG tensor at the iron site are sensitive to electronic and geometry structures. A relationship between the EFG tensor at the 14N and 17 O sites and the spin state of hemin complex is also detected.     

A computational study of a host-guest complex

The geometry and energetics of a complex involving pyrazine and an acridine diacid cleft-like host designed by Rebek were investigated at several levels of theory. Molecular mechanics (using the Tripos and CHARMm force fields), semiempirical quantum chemical approaches (with the AM1 and PM3 methods), and an ab initio quantum chemical method (RHF/STO-3G) were used in the complete relaxation of the complex. The geometry of the complex optimized by the RHF/STO-3G method is in excellent agreement with a published X-ray structure; upon superposition, the rms deviation between the corresponding cleft heavy atoms is only 0.17 Å and the pyrazine molecules are superimposable. In addition, ab initio quantum chemical techniques were used to study the complex when the cleft is modeled by a pair of acetic acid molecules. All the calculations presented herein support a two-point interaction mechanism. The similarities found in the results for the full complex and the truncated model are consistent with a purely structural role for the acridine linker of the host. © 1997 John Wiley & Sons, Ltd.     

Structure and energetics of small iron clusters

Electronic properties of Fe(2-10) clusters and their ions are described by an all-electron ab initio density functional theory computational analysis using the Handy's OPTX exchange and the gradient-corrected correlation functional of Perdew, Burke and Ernzerhof with a triple-zeta valence basis set plus polarization functions. Ground state structures, magnetic moments, dissociation energies, binding energies, IR vibrational spectra, vertical and adiabatic ionization energies, and electron affinities are reported. Two possible states for Fe(2) which are separated by 81.54 meV are described as possible Fe(2), while the septet (ground state) yields an accurate bond distance (error of 0.02??); the nonet yields a precise vibrational frequency (error of 10.1?cm(-1)). Fe(2) binding energy (0.05 eV/atom error) more closely resembles experimental data than any other previously reported computational methods. In addition, the Fe(6) is found to be the most stable cluster within our set being analyzed.     

Density-functional theory and ab initio Hartree-Fork studies on the structural parameters and chemical activity of the free radicals generated by benzoquinone and hydroquinone

Density-functional theory (DFT) calculations were performed for calculation of the theoretical spectra and the chemical activities of free radicals generated by benzoquinone and hydroquinone as well as the transition states, and the calculated spectra were used for the assignment of the frequencies observed in the experimental IR spectra. The calculated geometrical parameters, the predicted IR spectra, and the chemical activities of free radicals and transition states were also compared with those of benzoquinone and hydroquinone. The reactive mechanisms of free radicals generated by benzoquinone and hydroquinone are also discussed using ab initio Hartree-Fork (HF) methods.     

Electron Correlated Ab Initio Study of Amino Group Flexibility for Improvement of Molecular Mechanics Simulations on Nucleic Acid Conformations and Interactions

High level ab initio studies demonstrate substantial conformational flexibility of amino groups of nucleic acid bases. This flexibility is important for biological functions of DNA. Existing force field models of molecular mechanics do not describe this phenomenon due to a lack of quantitative experimental data necessary for an adjustment of empirical parameters. We have performed extensive calculations of nucleic acid bases at the MP2/6-31G(d,p) level of ab initio theory for broad set of amino group configurations. Two-dimensional maps of energy and geometrical characteristics as functions of two amino hydrogen torsions have been constructed. We approximate the maps by polynomial expressions, which can be used in molecular mechanics calculations. Detailed considerations of these maps enable us to propose a method for determination of numerical coefficients in the developed formulae using restricted sets of points obtained via higher-level calculations.     

Ab initio conformational maps for disaccharides in gas phase and aqueous solution

Ab initio conformational maps for beta-lactose in both the gas phase and in aqueous solution have been constructed at the HF/6-31G(d,p) level of calculation. The results of the gas-phase ab initio calculations allow us to conclude that a rigid conformational map is able to predict the regions of the minima in the potential energy surface of beta-lactose, in full agreement with those found in the relaxed conformational map. The solvation effects do not give rise to any new local minimum in the potential energy surface of beta-lactose, but just change the relative Boltzmann populations of the conformers found in the gas-phase calculations. The values obtained for heteronuclear spin coupling constant (3J(H,C)), using the seven most stable conformers in solution are in good agreement with the available experimental values. This is a good indication that ab initio rigid conformational maps can be reliably used to sort the most stable conformers of beta-lactose.     

Atomic resolution crystal structures and quantum chemistry meet to reveal subtleties of hydroxynitrile lyase catalysis

Hydroxynitrile lyases are versatile enzymes that enantiospecifically cope with cyanohydrins, important intermediates in the production of various agrochemicals or pharmaceuticals. We determined four atomic resolution crystal structures of hydroxynitrile lyase from Hevea brasiliensis: one native and three complexes with acetone, isopropyl alcohol, and thiocyanate. We observed distinct distance changes among the active site residues related to proton shifts upon substrate binding. The combined use of crystallography and ab initio quantum chemical calculations allowed the determination of the protonation states in the enzyme active site. We show that His(235) of the catalytic triad must be protonated in order for catalysis to proceed, and we could reproduce the cyanohydrin synthesis in ab initio calculations. We also found evidence for the considerable pK(a) shifts that had been hypothesized earlier. We envision that this knowledge can be used to enhance the catalytic properties and the stability of the enzyme for industrial production of enantiomerically pure cyanohydrins.     

The Hydrolysis Mechanism of Formamide Revisited: Comparison Between ab initio, Semiempirical and DFT Results

The hydrolysis of amides is a model reaction to study peptide hydrolysis. This process has been previously considered in the literature at the ab initio level. In this work, we revisit different reaction mechanisms (water-assisted, non-assisted, neutral and acid-catalyzed) with various theoretical methods : semiempirical, ab initio and Density Functional. The ab initio calculations are carried out at a computational level which is substantially higher than in previous studies. We describe the structure of the transition states and discuss the influence of the catalyst. We also compute the activation free energies for these processes at the Density Functional Theory level. Comparison of the methods allows to outline the main trends of these theoretical approaches which may be useful to design new computational strategies for investigating biological reaction mechanisms through the use of combined Quantum Mechanics/Molecular Mechanics methods.