Transition State For Isomerization Research Articles

Reversible Photocontrol of DNA Binding by a Designed GCN4-bZIP Protein

Synthetic photocontrolled proteins could be powerful tools for probing cellular chemistry. Several previous attempts to produce such systems by incorporating photoisomerizable chromophores into biomolecules have led to photocontrol but with incomplete reversibility, where the chromophore becomes trapped in one photoisomeric state. We report here the design of a modified GCN4-bZIP DNA-binding protein with an azobenzene chromophore introduced between Cys residues at positions 262 and 269 (S262C, N269C) within the zipper domain. As predicted, the trans form of the chromophore destabilizes the helical structure of the coiled-coil region of GCN4-bZIP, leading to diminished DNA binding relative to wild type. Trans-to-cis photoisomerization of the chromophore increases helical content and substantially enhances DNA binding. The system is observed to be readily reversible; thermal relaxation of the chromophore to the trans state and concomitant dissociation of the protein-DNA complex occurs with tau(1/2) approximately 10 min at 37 degrees C. It appears that conformational dynamics in the zipper domain make the transition state for isomerization readily available so that retention of reversible switching is observed.

Theoretical study on the isomeric structures and the stability of silylenoid (Tsi)Cl2SiLi (Tsi = C(SiMe3)3)

The structures and isomerization of silylenoid (Tsi)Cl(2)SiLi (Tsi = C(SiMe(3))(3)) were studied by density functional theory (DFT) at the B3LYP/6-31G(d) level. Four equilibrium structures and three isomeric transition states were located. The three-membered ring and p-complex structures, 1 and 2, are the two most stable forms. Two other local minima, the sigma-complex 3 and tetrahedron structure 4, should rearrange to 1 with very low barriers, and then to the most stable isomer 2. To exploit further the stability of silylenoid (Tsi)Cl(2)SiLi, the insertion reactions of 2 and silylene (Tsi)ClSi into the HF molecule have been investigated at the B3LYP/6-31G(d) level, respectively. The results show that the insertion of 2 into HF is very similar to that of (Tsi)ClSi into HF, but the latter is more favorable. To probe the influence of the substituent Tsi on the stability of silylenoid (Tsi)Cl(2)SiLi, the isomers and insertion reaction of silylenoid CH(3)Cl(2)SiLi were investigated in a similar way of those with (Tsi)Cl(2)SiLi. The results indicate that silylenoid containing very bulky group Tsi exhibits unusual stability because of the severe steric hindrance produced by Tsi at the center to which it is attached.

Characterization of the X̃A12, ÃB12, and X̃Π2 electronic states of the Ga2H molecule and the X̃A′2 and ÃA″2 isomerization transition states connecting the three minima

A wide range of highly correlated ab initio methods has been used to predict the geometrical parameters of the linear (X (2)Pi) and H-bridged (X (2)A(1) and A (2)B(1)) Ga(2)H isomers and two isomerization transition states (X (2)A(') and A (2)A(")) connecting the three minima. Dipole moments and vibrational frequencies are also obtained. The global minimum X (2)A(1) ground state of the H-bridged GaHGa isomer is predicted to lie only 1.6 [1.9 with the zero-point vibrational energy (ZPVE) corrections] kcal mol(-1) below the A (2)B(1) state. The X (2)A(1) state lies 5.4 kcal mol(-1) below the X (2)Pi ground state of the linear GaGaH isomer at the coupled-cluster with single, double, and perturbative triple excitations [CCSD(T)] level of theory with the augmented correlation-consistent polarized valence quadruple-zeta (aug-cc-pVQZ) basis set. The full triples coupled-cluster method is found to alter these CCSD(T) predictions by as much as 0.3 kcal mol(-1). The forward isomerization barriers from the linear ground state to the X (2)A(') and A (2)A(") transition states are determined to be 3.3 and 5.3 kcal mol(-1), respectively. The reverse isomerization barrier between the X (2)A(1) GaHGa structure and the X (2)Pi GaGaH structure is predicted to be 8.6 (8.2 with the ZPVE corrections) kcal mol(-1) at the aug-cc-pVQZ CCSD(T) level of theory.

Conformational Preference and Cis−Trans Isomerization of 4(R)-Substituted Proline Residues

We report here the conformational preference and prolyl cis-trans isomerization of 4(R)-substituted proline dipeptides, N-acetyl-N'-methylamides of 4(R)-hydroxy-L-proline and 4(R)-fluoro-L-proline (Ac-Hyp-NHMe and Ac-Flp-NHMe, respectively), studied at the HF/6-31+G(d), B3LYP/6-31+G(d), and B3LYP/6-311++G(d,p) levels of theory. The 4(R)-substitution by electron-withdrawing groups did not result in significant changes in backbone torsion angles as well as endocyclic torsion angles of the prolyl ring. However, the small changes in backbone torsion angles phi and psi and the decrease of bond lengths r(Cbeta-Cgamma) or r(Cgamma-Cdelta) appear to induce the increase of the relative stability of the trans up-puckered conformation and to alter the relative stabilities of transition states for prolyl cis-trans isomerization. Solvation free energies of local minima and transition states in chloroform and water were calculated using the conductor-like polarizable continuum model at the HF/6-31+G(d) level of theory. The population of trans up-puckered conformations increases in the order Ac-Pro-NHMe < Ac-Hyp-NHMe < Ac-Flp-NHMe in chloroform and water. The increase in population for trans up-puckered conformations in solution is attributed to the increase in population for the polyproline-II-like conformations with up puckering. The barriers DeltaGct++ to prolyl cis-to-trans isomerization for Ac-Hyp-NHMe and Ac-Flp-NHMe increase as the solvent polarity increases, as seen for Ac-Pro-NHMe. In particular, it was identified that the cis-trans isomerization proceeds through the clockwise rotation about the prolyl peptide bond for Ac-Hyp-NHMe and Ac-Flp-NHMe in chloroform and water, as seen for Ac-Pro-NHMe.

Insight into Selected Reactions in Low-Temperature Dimethyl Ether Combustion from Born−Oppenheimer Molecular Dynamics

Dimethyl ether is under consideration as an alternative diesel fuel. Its combustion chemistry is as yet ill-characterized. Here we use Born-Oppenheimer molecular dynamics (BOMD) based on DFT-B3LYP forces to investigate the short-time dynamics of selected features of the low-temperature dimethyl ether (DME) oxidation potential energy surface. Along the chain propagation pathway, we run BOMD simulations from the transition state involving the decomposition of (*)CH(2)OCH(2)OOH to two CH(2)=O and an (*)OH radical. We predict that formaldehyde C-O stretch overtones are excited, consistent with laser photolysis experiments. We also predict that O-H overtones are excited for the (*)OH formed from (*)CH(2)OCH(2)OOH dissociation. We also investigate short-time dynamics involved in chain branching. First, we examine the isomerization transition state of (*)OOCH(2)OCH(2)OOH --> HOOCH(2)OCHOOH. The latter species is predicted to be a short-lived metastable radical that decomposes within 500 fs to hydroperoxymethyl formate (HPMF; HOOCH(2)OC(=O)H) and the first (*)OH of chain branching. The dissociation of HOOCH(2)OCHOOH exhibits non-RRKM behavior in its lifetime profile, which may be due to conformational constraints or slow intramolecular vibrational energy transfer (IVR) from the nascent H-O bond to the opposite end of the radical, where O-O scission occurs to form HPMF and (*)OH. In a few trajectories, we see HOOCH(2)OCHOOH recross back to (*)OOCH(2)OCH(2)OOH because the isomerization is endothermic, with only an 8 kcal/mol barrier to recrossing. Therefore, some inhibition of chain-branching may be due to recrossing. Second, trajectories run from the transition state leading to the direct decomposition of HPMF (an important source of the second (*)OH radical in chain branching) to HCO, (*)OH, and HC(=O)OH show that these products can recombine to form many other possible products. These products include CH(2)OO + HC(=O)OH, H(2)O + CO + HC(=O)OH, HC(=O)OH + HC(=O)OH, and HC(=O)C(=O)H + H(2)O, which (save CH(2)OO + HC(=O)OH) are all more thermodynamically stable than the original HCO + (*)OH + HC(=O)OH products. Moreover, the multitude of extra products suggest that standard statistical rate theories cannot completely describe the reaction kinetics of significantly oxygenated compounds such as HPMF. These secondary products consume the second (*)OH required for explosive combustion, suggesting an inhibition of DME fuel combustion is likely.

A theoretical examination of the isomerization of BrONO 2 to BrOONO

The structural properties of the BrONO2 ↔ BrOONO isomerization transition states are examined using density functional calculations in conjunction with different basis sets. The energy barriers for the isomerization pathways at the CBS-QB3 level of theory are large enough, from 34.2 up to 32.5 kcal mol −1, to prevent the isomerization of BrONO 2 to either cis-perp or trans-perp BrOONO. But, the energy barriers of only 8.3 and 4.7 kcal mol −1 make feasible an interconversion process of cis-perp BrOONO and trans-perp BrOONO, respectively, to BrONO 2.

An ab initio study on structures and isomerization of magnesium chlorosilylenoid H 2SiClMgCl

The structures and isomerization of magnesium chlorosilylenoid H 2SiClMgCl were investigated by ab initio molecular orbital theory for the first time. Four equilibrium structures and three isomeric transition states were located and fully optimized at the G3MP2B3 level. For more accurate structural analysis, the B3LYP/cc-pVTZ and QCISD/6-311+G* calculations were performed, respectively. Based on the B3LYP/6-31G(d) optimized geometries, 29Si chemical shifts and harmonic frequencies of various structures were obtained. Isomerization paths for isomers were confirmed by the intrinsic reaction coordinate (IRC) calculations. Tetrahedral, three-membered ring and p-complex structures are suggested to be experimentally detectable ones. σ-Complex structure has the highest energy and will not exist. The solvent effects were considered by means of the polarizable continuum model (PCM) using THF as a solvent.

Reversibility of conformational switching in light-sensitive peptides

Reversible photo-control of protein structure and function is used by Nature to direct complex biological response to light. Reversibility is a feature that has been difficult to reliably achieve in analogous biomimetic systems. We report here measurement of the thermal and photoisomerization rates for peptide model systems in which isomerization of an intramolecularly linked azobenzene unit causes a helix-coil transition in the peptide. Reversibility is maintained and indeed the quantum yield for cis-to- trans photoisomerization is enhanced in these systems compared to an unstructured glutathione adduct of the chromophore alone. Reversibility can be understood by considering the intrinsic conformational preferences of the peptides to which the linkers are attached and how these preferences impact the stabilities of the transition states for isomerization.

New Insights into the Stereoselectivity of the Aryl Zinc Addition to Aldehydes

The addition of Ph(2)Zn to aldehydes has been investigated by DFT calculations. The experimentally observed increase in enantioselectivity upon addition of Et(2)Zn to the reaction mixture is rationalized from calculations of all isomeric transition states. Spectator ethyl groups in the transition state do not lower the intrinsic activation barrier, but instead increase it. In the presence of a bulky ligand, the inherently preferred all-phenyl transition state is selectively disfavored. The paths with less sterically demanding spectator ethyl groups will experience a more drastic ligand acceleration, and thus the influence of the ligand would be expected to be stronger in the presence of Et(2)Zn, in agreement with experimental observations.

Theoretical study on the structures and isomerization of silylenoid [( tert-butoxy)diphenylsilyl]lithium

The structures and isomerization of silylenoid Ph 2SiLi(OBu- t) were studied by density functional theory at B3LYP/6-31G(d) level. Four equilibrium structures and four isomeric transition states were located. Based on the B3LYP/6-31G(d) optimized geometries, the corresponding harmonic vibrational frequencies of transition states were obtained. The stability, reactivity and existence of various equilibrium structures were discussed.

DFT study of the mechanism of nitration of toluene with nitronium

AbstractReaction profiles of the isomeric nitration of toluene with nitronium ion were studied. Stationary points including three isomeric transition states were successfully located and characterized for the first time by employing hybrid DFT procedures at the B3LYP/6–311G** level without any restriction on the internal coordinates. Further correlation energy corrections by MP2/6–311G**//B3LYP/6–311G** were performed to evaluate the activation barrier heights. Mechanistic studies on the geometry, charge, energy and IR spectrum of the stationary points were carried out to illustrate the microscopic nitration process. A comparison of the nitrations of toluene and benzene shows that the methyl group plays dual roles in the nitration of toluene for its inductive and superconjugative effects. That is, the introduction of a methyl group creates favorable sites for the attacker and stabilizes the isomeric toluene–NO complexes. Both roles are critical to the positional selectivity. The order of the activation barrier height is para &lt; ortho &lt; benzene &lt; meta. This relative reactivity order is not changed with either B3LYP/6–311G** or MP2/6–311G**//B3LYP/6–311G** calculations, although the absolute magnitude of the latter is larger. The order of the stability of complexes is p‐toluene–NO &gt; o‐toluene–NO &gt; m‐toluene–NO &gt; benzene–NO. The relationship between the energy and the electron migration of NO2 group was established to elucidate the stabilization caused by the interaction between the two moieties of the complex. The vibrational shifts of tetrahedral C—N and C—H bonds suggest that the nitration of toluene may undergo the classical electrophilic substitution pathway, namely an SE2 mechanism. Copyright © 2004 John Wiley &amp; Sons, Ltd.

Peralkynylated buta-1,2,3-trienes: exceptionally low rotational barriers of cumulenic C=C bonds in the range of those of peptide C--N bonds.

A variety of 1,1,4,4-tetraal kynylbutatrienes and 1,4-dialkynylbutatrienes was synthezized by dimerization of the corresponding gem-dibromoolefins. Both (1)H and (13)C NMR spectroscopy indicated that the di- and tetraalkynylated butatrienes are formed as a mixture of cis and trans isomers. Variable temperature NMR studies evidenced a facile cis-trans isomerization, thus preventing the separation of these isomers by gravity or high-performance liquid chromatography (HPLC). For 1,1,4,4-tetraalkynylbutatrienes, the activation barrier deltaG( not equal ) was measured by magnetization transfer to be around 20 kcal mol(-1), in the range of the barrier for internal rotation about a peptide bond. Unlike the tetraalkynylated [3]cumulenes, 1,4-dialkynylbutatrienes are more difficult to isomerize and could, in one case, be obtained isomerically pure. Based on experimental data, the rotational barrier DeltaG( not equal ) for 1,4-dialkynylbutatrienes is estimated to be around 25 kcal mol(-1). The hypothesis of a stabilizing effect of the four alkynyl substituents on the proposed but-2-yne-1,4-diyl singlet diradical transition state of this cis-trans isomerization is further supported by a computational study.

Theoretical Study of the Straight-Chain C4H7 Radical Isomers and Their Dissociation and Isomerization Transition States

We use the G3//B3LYP method to calculate structures, harmonic vibrational frequencies, and energies at selected local minima and saddle points on the C4H7 potential energy surface. These include the straight-chain C4H7 radical isomers (of which there are twelve conformers of five structural isomers: 1-buten-1-yl, 2-buten-2-yl, 1-buten-2-yl, 1-methylallyl, and 3-buten-1-yl), sets of dissociation products, and dissociation, isomerization, and conformational transition states. Analogy with smaller hydrocarbon systems reveals why, for some reaction channels, more than one transition state may be accessed from the conformers of a structural isomer en route to the corresponding products. We compare results of the G3 and G3//B3LYP methods for selected C4H7 species.

Kinetics of the reaction of vinyl radicals with NO: Ab initio theory, master equation predictions, and laser absorption measurements

The pulsed laser photolysis/cw laser absorption technique is used to investigate the reaction of vinyl (C2H3) with NO in the temperature range from 295 to 700 K and pressures from 10 to 320 Torr (1.33 to 42.6 kPa). Vinyl radicals are generated by photolysis of vinyl iodide at 266 nm and detected by visible laser absorption in a vibronic band of the (A ← ) transition near 403 nm. The potential energy surface is explored with both quadratic configuration interaction and multi-reference configuration interaction ab initio calculations. These ab initio predictions are employed in RRKM theory based master equation simulations of the temperature and pressure dependent kinetics. At room temperature, the overall rate constant for removal of vinyl radical by NO is measured to be 1.6 ± 0.4 × 10−11 cm3 molecule−1 s−1, with negligible pressure dependence from 10 Torr (1.33 kPa) to 160 Torr (21.3 kPa) of helium. At constant pressure the rate constant decreases rapidly with temperature. At higher temperatures, a falloff of the rate constant to lower pressure is observed. The ab initio characterizations suggest a significant contribution from HCN + CH2O formation, with both isomerization transition states for the pathway leading to this product lying ∼15 kcal mol−1 (63 kJ mol−1) below the entrance channel. The master equation analysis provides a reasonably satisfactory reproduction of the observed kinetic data. The HCN + CH2O bimolecular channel, which proceeds from the addition complex through tight ring forming and opening transition states, has a negative temperature dependence and is the dominant channel for pressures of about 50 Torr (6.7 kPa) and lower. The theoretically predicted zero pressure rate coefficient is reproduced by the modified Arrhenius expression 5.02 × 10−11(T/298)−3.382exp(−516.3/T) cm3 molecule−1 s−1 (with T in K).

What is so special about Arg 55 in the catalysis of cyclophilin A? insights from hybrid QM/MM simulations.

Potential of mean force (PMF) simulations with a hybrid QM/MM potential function were used to analyze the catalytic mechanism of human cyclophilin A (CypA). PMF calculations were performed for proline isomerization of peptides in solution, the wild-type CypA, and several CypA mutants. With an approximate density functional theory, the self-consistent-charge density functional tight binding (SCC-DFTB) as the QM level, and CHARMM 22 force field as MM, satisfactory energetics compared to available experiments were obtained. Calculations for the Arg55Ala and zero-charge-Arg55 mutants clearly indicated that Arg 55 significantly stabilizes the isomerization transition state through electrostatic interactions. However, the decrease in the average distance (thus the increase in interaction) between Arg 55 and the substrate amide N in going from the stable states to the transition state is mainly due to the pyramidalization of the amide N rather than motions associated with Arg 55. Although the nanosecond simulations cannot exclude the existence of sub-millisecond collective motions proposed on the basis of recent elegant NMR relaxation and line-shape analyses, the energetics obtained for the various enzyme systems here indicate that the contribution from motions of active site residues to catalysis is expected to be small. Instead, the present simulations support that the structural stability rather than mobility of the preorganized active site is more important. Through hydrogen-bonding interactions among the substrate, Arg 55, Gln 63, and Asn 102, the active site of the wild-type enzyme is structurally very stable and puts Arg 55 in a favorable position to perform its catalytic role in the transition state. This is further illustrated with the somewhat unexpected prediction that Arg55Lys is largely catalytically inactive, because Lys does not have the unique bifurcating construct of the guanidino group in Arg and thus the active site of Arg55Lys cannot accommodate Lys in a position capable of providing electrostatic stabilization of the isomerization transition state. Among all the enzyme systems studied, the wild-type CypA is the only one that selects the syn/exo transition state, while the syn/endo conformation is also present in the mutants, which is another reason for their higher barriers. Finally, the present analysis indicated that the population of near-attack-conformations (NAC) is not relevant to catalysis in CypA.

Photodissociation of Methacrylonitrile at 193 nm: The CN Radical Product Channel

Photodissociation dynamics of methacrylonitrile (H2CC(CH3)CN) and 2-butenenitrile at 193 nm have been investigated by measuring laser induced fluorescence spectra of CN fragments. From the spectra, internal and translational energy distributions of CN have been obtained. For both molecules, the measured energy distributions are well represented by statistical prior calculations, assuming the CN and allyl radical products rather than the propenyl isomer. Ab initio calculations were performed for the relevant product species and transition states for isomerization and CN elimination. It has been concluded that methacrylonitrile dissociates in the ground electronic state via allyl cyanide formed by CN and H atom migration prior to dissociation. The quantum yield of the CN channel from methacrylonitrile was measured to be 0.012 ± 0.001.

A theoretical study on the isomerization of dicarba- closo-dodecaboranes

Within the limitations of AM1 (RHF) type semiempirical molecular orbital calculations, 1,2-; 1,7- and 1,12-dicarba- closo-dodecaboranes were considered. Their isomerization transition state geometries were determined and vibrational spectra for the transition states were obtained by using quadratic synchronous change method.

Accurate ab initio spectroscopic properties of HOPx and HPOx (x=−1,0,+1)

The structure, rotational constants, vibrational frequencies and stability of HOPx and HPOx (x=−1,0,+1) anion, cation, and neutral species have been studied with the coupled cluster method using a variety of cc-pVXZ and aug-cc-pVXZ Dunning basis sets. HPO is more stable than the HOP isomer. The energy difference is 34.2 kcal mol−1. HPO is bound with respect to dissociation into H + PO by 65.5 kcal mol−1. HOP is 15.4 kcal mol−1 lower in energy on the triplet surface than HOP on the singlet surface, suggesting that HOP (3A″) is the ground state for HOP. The isomerization barrier of HPO to HOP is estimated to be 64.7 kcal mol−1 on the singlet surface. Dissociation of HPO into H + PO is found to be competitive with its isomerization. The ionization energy of HPO is calculated to be 239.9 kcal mol−1, and its electron affinity is 22.5 kcal mol−1. Structural and energetic properties of the cation and anion of HPO and HOP are reported for the first time. Isomerization transition states and barriers have been located for both the cation and anion. The isomerization barrier for HOP+→HPO+ is quite high, suggesting that the cation of HOP should be experimentally observable.

Hydrogen Atom Adducts to the Amide Bond. Generation and Energetics of Amide Radicals in the Gas Phase

The 1-hydroxy-1-(N-methyl)aminoethyl radical (1) represents a simple model system for hydrogen atom adducts to the amide bond in gas-phase peptide and protein ions relevant to electron capture dissociation (ECD). Radical 1 was generated in the rarefied gas phase by femtosecond electron transfer to the stable cation prepared by selective O-protonation of N-methylacetamide. The main dissociations of 1 were loss of the hydroxyl hydrogen atom and the N-methyl group in a 1.7:1 ratio, as deduced from product analysis and deuterium labeling. The dissociations that occur on the 4.1 microsecond time scale are driven by large Franck−Condon effects on collisional electron transfer that deposit 93−103 kJ mol-1 in the nascent radicals. Detailed analysis of the potential energy surface for dissociations of 1 revealed several conformers and isomeric transition states for dissociations of the O−H and N−CH3 bonds. The experimental branching ratio is in quantitative agreement with RRKM calculations within the accuracy of t...

Signal transduction in the photoactive yellow protein. I. Photon absorption and the isomerization of the chromophore.

Molecular dynamics simulation techniques together with time-dependent density functional theory calculations have been used to investigate the effect of photon absorption by a 4-hydroxy-cinnamic acid chromophore on the structural properties of the photoactive yellow protein (PYP) from Ectothiorodospira halophila. The calculations suggest that the protein not only modifies the absorption spectrum of the chromophore but also regulates the subsequent isomerization of the chromophore by stabilizing the isomerization transition state. Although signaling from PYP is thought to involve partial unfolding of the protein, the mechanical effects accompanying isomerization do not appear to directly destabilize the protein.