Ahmet Altun

Structure and vibrational spectra of p-methylaniline: Hartree-Fock, MP2 and density functional theory studies

Abstract The FT-IR and FT-Raman spectra of p-methylaniline (pMA) have been recorded. Optimized molecular structures and normal vibrations of pMA have been obtained from the HF, MP2 and DFT-B3LYP methods implementing the 6-31G* and 6-31G** basis sets. Scale factors, which bring computational frequencies in closer agreement with the experimental data, have been calculated for predominant vibrational motions of the normal modes at each level considered. All observed harmonic IR and Raman bands of pMA have been assigned in the frameworks of the calculations. The assignments have been compared each other and with the 30 benzene-like modes. The effects of the methyl and amino substituents on vibrational frequencies have been investigated. The applicability limits of HF, MP2 and DFT-B3LYP methods have been discussed. The DFT-B3LYP method has been found very promising for vibrational spectral analyses.

Theoretical and experimental studies of the vibrational spectra of m-methylaniline

The FT-IR and FT-Raman spectra of m-methylaniline (mMA) have been recorded. Optimized molecular structures and normal vibrations of mMA have been obtained from the ab initio-HF and the DFT-B3LYP levels. The 6-31G* basis set has been used for each level of calculations. Correction factors, which bring computational frequencies in closer agreement with the experimental data, have been calculated for predominant vibrational motions of the normal modes at each level of theory. All IR and Raman bands of mMA have been assigned in the frameworks of the calculations. The assignments have been compared each other and with the 30 benzene-like modes. The DFT-B3LYP/6-31G* calculations have been found more reliable than the ab initio-MP2/6-31G* calculations for the vibrational study of mMA.

Spectral Tuning in Visual Pigments: An ONIOM(QM:MM) Study on Bovine Rhodopsin and its Mutants

We have investigated geometries and excitation energies of bovine rhodopsin and some of its mutants by hybrid quantum mechanical/molecular mechanical (QM/MM) calculations in ONIOM scheme, employing B3LYP and BLYP density functionals as well as DFTB method for the QM part and AMBER force field for the MM part. QM/MM geometries of the protonated Schiff-base 11- cis-retinal with B3LYP and DFTB are very similar to each other. TD-B3LYP/MM excitation energy calculations reproduce the experimental absorption maximum of 500 nm in the presence of native rhodopsin environment and predict spectral shifts due to mutations within 10 nm, whereas TD-BLYP/MM excitation energies have red-shift error of at least 50 nm. In the wild-type rhodopsin, Glu113 shifts the first excitation energy to blue and accounts for most of the shift found. Other amino acids individually contribute to the first excitation energy but their net effect is small. The electronic polarization effect is essential for reproducing experimental bond length alternation along the polyene chain in protonated Schiff-base retinal, which correlates with the computed first excitation energy. It also corrects the excitation energies and spectral shifts in mutants, more effectively for deprotonated Schiff-base retinal than for the protonated form. The protonation state and conformation of mutated residues affect electronic spectrum significantly. The present QM/MM calculations estimate not only the experimental excitation energies but also the source of spectral shifts in mutants.

Systematic QM/MM investigation of factors that affect the cytochrome P450‐catalyzed hydrogen abstraction of camphor

The hydrogen abstraction reaction of camphor in cytochrome P450cam has been investigated in the native enzyme environment by combined quantum mechanical/molecular mechanical (QM/MM) calculations and in the gas phase by density functional calculations. This work has been motivated by contradictory published QM/MM results. In an attempt to pinpoint the origin of these discrepancies, we have systematically studied the factors that may affect the computed barriers, including the QM/MM setup, the optimization procedures, and the choice of QM region, basis set, and protonation states. It is found that the ChemShell and QSite programs used in the published QM/MM calculations yield similar results at given geometries, and that the discrepancies mainly arise from two technical issues (optimization protocols and initial system preparation) that need to be well controlled in QM/MM work. In the course of these systematic investigations, new mechanistic insights have been gained. The crystallographic water 903 placed near the oxo atom of Compound I lowers the hydrogen abstraction barrier by ca. 4 kcal/mol, and thus acts as a catalyst for this reaction. Spin density may appear at the A‐propionate side chain of the heme if the carboxylate group is not properly screened, which might be expected to happen during protein dynamics, but not in static equilibrium situations. There is no clear correlation between the computed A‐propionate spin density and the hydrogen abstraction barrier, and hence, no support for a previously proposed side‐chain mediated transition state stabilization mechanism. Standard QM/MM optimizations yield an A‐propionate environment close to the X‐ray structure only for protonated Asp297, and not for deprotonated Asp297, but the computed barriers are similar in both cases. An X‐ray like A‐propionate environment can also be obtained when deprotonated Asp297 is included in the QM region and His355 is singly protonated, but this Compound II‐type species with a closed‐shell porphyrin ring has a higher hydrogen abstraction barrier and should thus not be mechanistically relevant.

Thermal studies and vibrational analyses of m-methylaniline complexes of Zn(II), Cd(II) and Hg(II) bromides.

The complexes having the MBr(2)L(2) (M: Zn, Cd and Hg; L: m-methylaniline) formulae have been prepared and characterized by their elemental analyses, thermogravimetric analyses, IR and Raman spectral studies. IR and Raman bands of the complexes have been assigned as compared with the free ligand. Coordination effects on the internal modes of m-methylaniline have been discussed. Vibrational spectra propose that the [ZnBr(2)(mMA)(2)] complex is in a tetrahedral environment around Zn(II) ion with C(2v) symmetry whereas Cd(II) and Hg(II) complexes have 5-coordinate polymeric bromide bridged structures.

Common system setup for the entire catalytic cycle of cytochrome P450cam in quantum mechanical/molecular mechanical studies

We describe a system setup that is applicable to all species in the catalytic cycle of cytochrome P450cam. The chosen procedure starts from the X‐ray coordinates of the ferrous dioxygen complex and follows a protocol that includes the careful assignment of protonation states, comparison between different conceivable hydration schemes, and system preparation through a series of classical minimizations and molecular dynamics (MD) simulations. The resulting setup was validated by quantum mechanical/molecular mechanical (QM/MM) calculations on the resting state, the pentacoordinated ferric and ferrous complexes, Compound I, the transition state and hydroxo intermediate of the CH hydroxylation reaction, and the product complex. The present QM/MM results are generally consistent with those obtained previously with individual setups. Concerning hydration, we find that saturating the protein interior with water is detrimental and leads to higher structural flexibility and catalytically inefficient active‐site geometries. The MD simulations favor a low water density around Asp251 that facilitates side chain rotation of protonated Asp251 during the conversion of Compound 0 to Compound I. The QM/MM results for the two preferred hydration schemes (labeled SE‐1 and SE‐4) are similar, indicating that slight differences in the solvation close to the active site are not critical as long as camphor and the crystallographic water molecules preserve their positions in the experimental X‐ray structures.

Correlated Ab Initio and Density Functional Studies on H2 Activation by FeO(.).

The reaction FeO(+) + H2 → Fe(+) + H2O is a simple model for hydrogen abstraction processes in biologically important heme systems. The geometries of all relevant stationary points on the lowest sextet and quartet surfaces were optimized using several density functionals as well as the CASSCF method. The corresponding energy profiles were computed at the following levels: density functional theory using gradient-corrected, hybrid, meta, hybrid-meta, and perturbatively corrected double hybrid functionals; single-reference coupled cluster theory including up to single, double, triple, and perturbative quadruple excitations [CCSDT(Q)]; correlated multireference ab initio methods (MRCI, MRAQCC, SORCI, SORCP, MRMP2, NEVPT2, and CASPT2). The calculated energies were corrected for scalar relativistic effects, zero-point vibrational energies, and core-valence correlation effects. MRCI and SORCI energies were corrected for size-consistency errors using an a posteriori Davidson correction (+Q) leading to MRCI+Q and SORCI+Q. Comparison with the available experimental data shows that CCSDT(Q) is most accurate and can thus serve as benchmark method for this electronically challenging reaction. Among the density functionals, B3LYP performs best. In the correlated ab initio calculations with a full-valence active space, SORCI+Q yields the lowest deviations from the CCSDT(Q) reference results, with qualitatively similar energy profiles being obtained from MRCI+Q and MRAQCC. SORCI+Q benefits from the quality of the approximate average natural orbitals used in the final step of the SORCI procedure. Many of the tested methods show surprisingly large errors. The present results validate the common use of B3LYP in computational studies of heme systems and offer guidance on which correlated ab initio methods are most suitable for such studies.

Color Tuning in Short Wavelength-Sensitive Human and Mouse Visual Pigments: Ab initio Quantum Mechanics/Molecular Mechanics Studies

We have investigated the protonation state and photoabsorption spectrum of Schiff-base (SB) nitrogen bound 11-cis-retinal in human blue and mouse UV cone visual pigments as well as in bovine rhodopsin by hybrid quantum mechanical/molecular mechanical (QM/MM) calculations. We have employed both multireference (MRCISD+Q, MR-SORCI+Q, and MR-DDCI2+Q) and single reference (TD-B3LYP and RI-CC2) QM methods. The calculated ground-state and vertical excitation energies show that UV-sensitive pigments have deprotonated SB nitrogen, while violet-sensitive pigments have protonated SB nitrogen, in agreement with some indirect experimental evidence. A significant blue shift of the absorption maxima of violet-sensitive pigments relative to rhodopsins arises from the increase in bond length alternation of the polyene chain of 11-cis-retinal induced by polarizing fields of these pigments. The main counterion is Glu113 in both violet-sensitive vertebrate pigments and bovine rhodopsin. Neither Glu113 nor the remaining pigment has a significant influence on the first excitation energy of 11-cis-retinal in the UV-sensitive pigments that have deprotonated SB nitrogen. There is no charge transfer between the SB and beta-ionone terminals of 11-cis-retinal in the ground and first excited states.

Quantum Mechanical/Molecular Mechanical Studies on Spectral Tuning Mechanisms of Visual Pigments and Other Photoactive Proteins†

The protein environments surrounding the retinal tune electronic absorption maximum from 350 to 630 nm. Hybrid quantum mechanical/molecular mechanical (QM/MM) methods can be used in calculating excitation energies of retinal in its native protein environments and in studying the molecular basis of spectral tuning. We hereby review recent QM/MM results on the phototransduction of bovine rhodopsin, bacteriorhodopsin, sensory rhodopsin II, nonretinal photoactive yellow protein and their mutants.

Multireference Ab Initio Quantum Mechanics/Molecular Mechanics Study on Intermediates in the Catalytic Cycle of Cytochrome P450cam

We have investigated the elusive reactive species of cytochrome P450(cam) (Compound I), the hydroxo complex formed during camphor hydroxylation, and the ferric hydroperoxo complex (Compound 0) by combined quantum mechanical/molecular mechanical (QM/MM) calculations, employing both density functional theory (DFT) and correlated ab initio methods. The first two intermediates appear multiconfigurational in character, especially in the doublet state and less so in the quartet state. DFT(B3LYP)/MM calculations reproduce the relative energies from correlated ab initio QM/MM treatments quite well, except for the splitting of the lowest A(1u)-A(2u) radical states. The inclusion of dynamic correlation is crucial for the proper ab initio treatment of these intermediates.