Sabyashachi Mishra

Atomistic simulation of NO dioxygenation in group I truncated hemoglobin.

NO dioxygenation, i.e., the oxidation of nitric oxide to nitrate by oxygen-bound truncated hemoglobin (trHbN) is studied using reactive molecular dynamics simulations. This reaction is an important step in a sequence of events in the overall NO detoxification reaction involving trHbN. The simulations ( approximately 160 ns in total) reveal that the reaction favors a pathway including (i) NO binding to oxy-trHbN, followed by (ii) rearrangement of peroxynitrite-trHbN to nitrato-trHbN, and finally (iii) nitrate dissociation from nitrato-trHbN. Overall, the reactions occur within tens of picoseconds and the crossing seam of the reactant and product are found to be broad. The more conventional pathway, where the peroxynitrite-trHbN complex undergoes peroxide cleavage to form free NO(2) and oxo-ferryl trHbN, is found to be too slow due to a considerable barrier involved in peroxide bond dissociation. The energetics of this step is consistent with earlier electronic structure calculations and make this pathway less likely. The role of Tyr33 and Gln58 in the NO dioxygenation has been investigated by studying the reaction in mutants of trHbN. The mutation study suggests that residues Tyr33 and Gln58 preorient the reactive ligands through a highly dynamical H-bonding network which facilitates the reaction. In particular, the Y33A mutation leads to a significant retardation in NO dioxygenation, in agreement with experiments which reveal a strong influence of the protein environment on the reaction rate.

Nitric Oxide Dynamics in Truncated Hemoglobin: Docking Sites, Migration Pathways, and Vibrational Spectroscopy from Molecular Dynamics Simulations

Atomistic simulations of nitric oxide (NO) dynamics and migration in the trHbN of Mycobacterium tuberculosis are reported. From extensive molecular dynamics simulations (48 ns in total), the structural and energetic properties of the ligand docking sites in the protein have been characterized and a connectivity network between the ligand docking sites has been built. Several novel migration and exit pathways are found and are analyzed in detail. The interplay between a hydrogen-bonding network involving residues Tyr(33) and Gln(58) and the bound O(2) ligand is discussed and the role of Phe(62) residue in ligand migration is examined. It is found that Phe(62) is directly involved in controlling ligand migration. This is reminiscent of His(64) in myoglobin, which also plays a central role in CO migration pathways. Finally, infrared spectra of the NO molecule in different ligand docking sites of the protein are calculated. The pocket-specific spectra are typically blue-shifted by 5-10 cm(-1), which should be detectable in future spectroscopic experiments.

Quantitative Analysis of Ligand Migration from Transition Networks

In this work we use transition network analysis for the first time to investigate ligand migration in truncated hemoglobin (trHbN) and obtain kinetic information about the docking-site dynamics in the protein. A comparison with explicit water molecular dynamics simulations (100 ns in total) shows that the rate constants derived from the network analysis are realistic. The transition network analysis provides 1) The time-resolved connectivity network in the protein; 2) The half-lives of the docking sites; 3) The transition timescales between two given docking sites; and 4) The extent of population transfer among different docking sites of the protein as a function of lag time. We investigate the role of the Tyr33 and Gln58 residues in ligand migration by studying ligand migration in four mutants of trHbN. The mutation study suggests that residues Tyr33 and Gln58 stabilize the NO ligand in the Xe2 docking site of trHbN, thus facilitating the efficiency of the NO detoxification reaction.

Spin-orbit vibronic coupling in Π3 states of linear triatomic molecules

The Renner-Teller vibronic-coupling problem of a 3Pi electronic state of a linear molecule is analyzed with the inclusion of the spin-orbit coupling of the 3Pi electronic state, employing the microscopic (Breit-Pauli) spin-orbit coupling operator for the two unpaired electrons. The 6x6 Hamiltonian matrix in a diabatic spin-electronic basis is obtained by an expansion of the molecular Hamiltonian in powers of the bending amplitude. The symmetry properties of the Hamiltonian with respect to the time-reversal operator and the relativistic vibronic angular momentum operator are analyzed. It is shown that there exists a linear vibronic-coupling term of spin-orbit origin, which has not been considered so far in the Renner-Teller theory of 3Pi electronic states. While two of the six adiabatic electronic wave functions do not exhibit a geometric phase, the other four carry nontrivial topological phases which depend on the radius of the integration contour. The spectroscopic effects of the linear spin-orbit vibronic-coupling mechanism have been analyzed by numerical calculations of the vibronic spectrum for selected model examples.

Structural Diversity of Copper(I) Complexes Formed by Pyrrole- and Dipyrrolylmethane-Based Diphosphine Ligands with Cu–X···HN Hydrogen Bonds

Metal complexes containing hydrogen bond donor/acceptor groups are interesting because of their applications in several areas. In the course of our investigation on the synthesis of metal complexes using newly developed pyrrole-based diphosphine ligands, a few structurally interesting copper(I) complexes containing the pyrrolic NH hydrogen bond donors were synthesized. The reaction of 2,5-bis(diphenylphosphinomethyl)pyrrole (PNP) with an equimolar quantity of CuX (X = Cl, Br, and I) afforded the binuclear copper(I) complexes [Cu(μ-X)(μ-PNP-P,P)]2 (1-3) in very good yields (87-90%). Conversely, the analogous reaction between 1,9-bis(diphenylphosphinomethyl)diphenyldipyrrolylmethane (PNNP) and CuX (X = Cl, Br, and I) yielded the mononuclear Cu(I) complexes [CuX(PNNP-P,P)] (4-6) in very good yields (∼88%), in which the diphosphine ligand is chelated to the copper metal atom. Interestingly, when this reaction was carried out with a 1:2 mol ratio of ligand/metal, the cubane-like tetranuclear Cu(I) complex, [Cu4I4{μ-Ph2C(C4H3N)2-1,9-(CH2PPh2)2-P,P}2] 7, was isolated in 68% yield. In addition, the reaction between the dipyrrolyldiphosphine ligand (PNNP) and CuCl in the presence of 1 equiv of 1,10-phenanthroline monohydrate and NaBF4 afforded a novel ionic binuclear mixed-ligand Cu(I) complex, [Cu2(μ-X)(μ-PNNP-P,P)(NN)2]BF4 8, where NN = 1,10-phenanthroline in 57% yield. The structures of all these complexes were confirmed by the single-crystal X-ray diffraction method and are supported by spectroscopic data. In contrast to the PNP pincer ligand, the dipyrrolyl-diphosphine ligand (PNNP) adopts chelation as well as bridging coordination modes with Cu(I) atoms, indicating its flexibility of bonding. In all the structures, the Cu-X···HN type of hydrogen bonds involving the metal halide ion as acceptor and the pyrrolic NH as donor are present with the Cu-X···H angles, which deviate from the favored 90°, as observed in their solid state structures. Further, the presence of this type of hydrogen bond was confirmed by NBO, AIM, and Hirshfeld analyses.

Calculation of the vibronic structure of the X̃Π2 photoelectron spectra of XCN,X=F, Cl, and Br

The vibronic structure of the photoelectron spectra of the X (2)Pi state of XCN(+) (X=F, Cl, and Br) has been calculated, assuming that the X (2)Pi state can be considered as an isolated electronic state. The Renner-Teller coupling of the two components of the (2)Pi state via the degenerate bending mode as well as spin-orbit coupling effects are taken into account. The two stretching modes are treated within the so-called linear vibronic-coupling model. The vibronic and spin-orbit parameters have been determined by accurate ab initio electronic-structure calculations. While spin-orbit effects are small in FCN(+), the large spin-orbit splitting of the X (2)Pi state of the BrCN(+) leads to a complete quenching of the Renner-Teller effect. The X (2)Pi state of the ClCN(+) is shown to be of particular interest: here the resonance condition for linear-relativistic Renner-Teller coupling is approximately fulfilled. This coupling mechanism leads to a significant intensity transfer to vibronic levels with odd quanta of the bending mode. The calculated spectrum indicates that this novel relativistic vibronic-coupling effect should be observable in high-resolution (electron energy resolution of the order of a few meV) photoelectron spectra of ClCN.

Renner-Teller and spin-orbit vibronic coupling effects in linear triatomic molecules with a half-filled π shell

The vibronic and spin-orbit-induced interactions among the (3)Sigma(-), (1)Delta, and (1)Sigma(+) electronic states arising from a half-filled pi orbital of a linear triatomic molecule are considered, employing the microscopic (Breit-Pauli) spin-orbit coupling operator. The 6 x 6 Hamiltonian matrix is derived in a diabatic spin-orbital electronic basis set, including terms up to fourth order in the expansion of the molecular Hamiltonian in the bending normal coordinate about the linear geometry. The symmetry properties of the Hamiltonian are analyzed. Aside from the nonrelativistic fourth-order Renner-Teller vibronic coupling within the (1)Delta state and the second-order nonrelativistic vibronic coupling between the (1)Sigma(+) and (1)Delta states, there exist zeroth-order, first-order, as well as third-order vibronic coupling terms of spin-orbit origin. The latter are absent when the phenomenological expression for the spin-orbit coupling operator is used instead of the microscopic form. The effects of the nonrelativistic and spin-orbit-induced vibronic coupling mechanisms on the (3)Sigma(-), (1)Delta, and (1)Sigma(+) adiabatic potential energy surfaces as well as on the spin-vibronic energy levels are discussed for selected parameter values.

Calculation of the vibronic structure of the photodetachment spectra of CCCl− and CCBr−

The vibronic structure of the closely spaced and strongly coupled X 2Sigma+ and A 2Pi states in the photodetachment spectra of CCCl- and CCBr- has been calculated by considering Sigma-Pi vibronic coupling together with spin-orbit coupling. The stretching modes are treated within the so-called linear-vibronic-coupling model. The vibronic and spin-orbit parameters have been determined by accurate ab initio electronic-structure calculations. While the nonrelativistic vibronic-coupling parameters are of approximately equal strength in CCCl and CCBr, the vibronic-coupling parameters of spin-orbit origin are found to be larger in the latter. The calculated photodetachment spectra of both systems are shown to exhibit a complicated vibronic structure due to strong Sigma-Pi vibronic coupling. The spectral envelopes of the calculated photodetachment spectra exhibit a double-hump reminiscent of strongly coupled Exe Jahn-Teller systems.

Quasiclassical theory of the dynamical E × E Jahn–Teller effect including spin–orbit interaction

The dynamical Jahn–Teller effect including spin–orbit coupling is considered in the coordinate and momentum representations of the nuclear motion. The momentum representation is used for the asymptotical solution of the dynamical equations in the quasiclassical Landau–Zener parametric limiting case. Vibronic energy levels of the E × E Jahn–Teller effect with spin–orbit coupling are calculated from the quasiclassical secular equation. They are compared with numerically exact energy levels obtained by the diagonalization of the Hamiltonian matrix in a harmonic oscillator basis. The comparison reveals reasonable accuracy of the quasiclassical approximation for a wide range of quantum numbers and system parameters. The quasiclassical analysis provides insight into the nature of the non-adiabatic dynamics of E × E Jahn–Teller systems with spin–orbit coupling.

Quantum-mechanical DFT calculation supported Raman spectroscopic study of some amino acids in bovine insulin.

In this article Quantum mechanical (QM) calculations by Density Functional Theory (DFT) have been performed of all amino acids present in bovine insulin. Simulated Raman spectra of those amino acids are compared with their experimental spectra and the major bands are assigned. The results are in good agreement with experiment. We have also verified the DFT results with Quantum mechanical molecular mechanics (QM/MM) results for some amino acids. QM/MM results are very similar with the DFT results. Although the theoretical calculation of individual amino acids are feasible, but the calculated Raman spectrum of whole protein molecule is difficult or even quite impossible task, since it relies on lengthy and costly quantum-chemical computation. However, we have tried to simulate the Raman spectrum of whole protein by adding the proportionate contribution of the Raman spectra of each amino acid present in this protein. In DFT calculations, only the contributions of disulphide bonds between cysteines are included but the contribution of the peptide and hydrogen bonds have not been considered. We have recorded the Raman spectra of bovine insulin using micro-Raman set up. The experimental spectrum is found to be very similar with the resultant simulated Raman spectrum with some exceptions.