Self-consistent Reaction Field Research Articles

Inverted Cucurbit[n]urils: Density Functional Investigations on the Electronic Structure, Electrostatic Potential, and NMR Chemical Shifts

Inverted cucurbit[n]uril (i(x)CB[n], x = 1, 2; n = 6-8), the enantiomers of cucurbit[n]uril (CB[n]) comprising one or more inverted glycouril units, show distinct selectivity in recognition toward the guest by the virtue of shape and dimensions of its cavity. The iCB[n] (x = 1 and n = 6, 7) are isolated as intermediates during the synthesis of CB[n]. In this work, density functional theory using the hybrid B3LYP functional has been employed to derive the electronic structure and the NMR chemical shifts in the i(x)CB[n] hosts. The present calculations have shown that the inversion of the glycouril unit of CB[6] and CB[7] engenders a destabilization by 4.2 and 5.7 kJ mol(-1), respectively, and, as opposed to this, the iCB[8] is favored by 18.6 kJ mol(-1) over the corresponding CB[8] host. Likewise, i2CB[7] possessing two inverted glycourils are highly destabilized over CB[7]. A large separation of the inverted glycouril units reduces the repulsion between methine protons inside the cavity, rendering the 1,4-i2CB[n] (n = 7 or 8) to be of lowest energy. Stabilization energies from the self-consistent reaction field (SCRF) theory are calculated with water, ethanol, and tetrahydrofuran (THF) as solvents. Unlike in gas phase and other solvents, the stabilization hierarchy iCB[6] < iCB[7] < iCB[8] has been predicted in THF. Molecular electrostatic potential (MESP) was used to gauge the cavity shape of these hosts. Consequently the iCB[6] reveals a half-sprocket-like cavity; an additional tooth for each glycouril in the succeeding iCB[n] homologue was noticed. In the case of the 1,5-i2CB[8] enantiomer, the cavity turns out to be rectangular. The deeper MESP minima near the ureido oxygens suggest strong electrostatic interactions with the guest at the iCB[6] portals. The electron-rich region within the cavity explains the large affinity of CB[n] toward the electron deficient guests. The electronic distribution and shape and size of the cavity thus derived provide insights for the inclusion of guests of different shapes in a variety of i(x)CB[n] hosts. NMR chemical shifts have shown that the methylene protons near the inverted glycouril and the methine protons those are directing toward the cavity yield distinct signals, consistent with those observed in experiments. The protons within the cavity are less affected by solvation.

Alkali metals (Li, Na, and K) in methyl phosphodiester hydrolysis

The phosphodiester linkage central to biological systems has been modeled by methyl phosphodiester (MPDE) in various theoretical and experimental studies. Under physiological conditions, hydrolysis of the phosphodiester is negligible, however this process can be catalyzed in the presence of metal ions. To understand the role of alkali metals in MPDE hydrolysis and, in particular, how it influences the reaction pathway and the associated energetics, density functional calculations employing the 6-31+G(d,p) basis set have been carried out. Different pathways that include the reactant, intermediates and the products have been investigated for MPDE hydrolysis catalyzed by one or two lithium ions, characterized as stationary point geometries on the potential energy surface. The pathways A and B incorporate a single lithium ion bonded to different oxygens of the diester functionality. In pathway C, a six-membered ring was noticed wherein the nucleophile bridges two lithium ions interacting with different oxygens of the phosphoryl group. Furthermore, in the pathway (D) incorporating two lithium ions, one of the lithium ions interacts with the hydroxyl group and another with the methoxy oxygen; both metal ions are coordinated by the same phosphoryl oxygen. In addition to this, yet another pathway (E), where the metal ions are bound to different oxygens of the phosphoryl group, has also been dealt with. The calculations have shown that the A and B pathways lead to a single step reaction. A three-step mechanism including the nucleophilic (hydroxyl) attack, rotation of a methyl group and, finally, departure of the methoxy group has been predicted for the D and E profiles. Both D and E pathways are favored equally (with a marginal difference of 0.3 kJ mol(-1) in their activation energies) in the gas phase and a transition state corresponding to nucleophilic attack with an energy barrier of 32.5 kJ mol(-1) was located when lithium was used. A penta-coordinated phosphorous intermediate on the potential energy surface was characterized along these pathways. MPDE hydrolysis yielded a lower energy barrier for lithium than those for the remaining alkali metal ions. This agrees well with the experimentally observed trend for the hydrolysis rates: Li > Na > K. Self consistent reaction field (SCRF) calculations reveal the lower energy barrier between the reactant and the transition state for the nucleophilic attack in nonpolar solvents. The extent of bond formation (or cleavage) in different stationary point structures along the reaction path as estimated from the electron density at the bond critical point in the molecular electron density topography, has proven useful in distinguishing the associative or dissociative reaction pathways.

Theoretical study of solvent effect on one- and two-photon absorption properties of starburst DCM derivatives

The equilibrium geometries, electronic structures, one-photon absorption (OPA) and two-photon absorption (TPA) properties of starburst 4-(dicyanomethylene)-2-methyl-6-[p-(dimethylamino)styryl]-4H-pyran (DCM) derivatives have been studied by using density functional theory (DFT) and Zerner's intermediate neglect of differential overlap (ZINDO) program. Results showed that increasing the number of branches in DCM molecules and introducing stronger electron withdrawing groups are efficient ways to enhance the TPA cross sections. For the two- and three-branched molecules of the DCM derivatives, the solvent effect on the OPA and TPA properties was also considered by adapting the self-consistent reaction field (SCRF) theory with the polarizable continuum model (PCM) to model the interaction with the solvent in ZINDO program. The calculated molecular structure, transition dipole moment and intramolecular charge transfer (ICT) in different solvents have been analyzed to approximate how the solvent affects the TPA cross section. Results indicated that the TPA cross section increases as the polarity of the solvents increases, and it reaches a maximum when the dielectric constant epsilon equals 20.7.

DFT calculations of comparative energetics and ENDOR/Mössbauer properties for two protonation states of the iron dimer cluster of ribonucleotide reductase intermediate X.

Two models (I and II) for the active site structure of class-I ribonucleotide reductase (RNR) intermediate X in subunit R2 have been studied in this paper, using broken-symmetry density functional theory (DFT) incorporated with the conductor like screening (COSMO) solvation model and with the finite-difference Poisson-Boltzmann self-consistent reaction field (PB-SCRF) calculations. Only one of the bridging groups between the two iron centers is different between model-I and model-II. Model-I contains two mu-oxo bridges, while model-II has one bridging oxo and one bridging hydroxo. These are large active site models including up to the fourth coordination shell H-bonding residues. Mössbauer and ENDOR hyperfine property calculations show that model-I is more likely to represent the active site structure of RNR-X. However, energetically our pK(a) calculations at first highly favored the bridging oxo and hydroxo (in model-II) structure of the diiron center rather than having the di-oxo bridge (in model-I). Since the Arg236 and the nearby Lys42, which are very close to the diiron center, are on the protein surface of RNR-R2, it is highly feasible that one or two anion groups in solution would interact with the positively charged side chains of Arg236 and Lys42. The anion group(s) can be a reductant, phosphate, sulfate, nitrate, and other negatively charged groups existing in biological environments or in the buffer of the experiment. Since sulfate ions certainly exist in the buffer of the ENDOR experiment, we have examined the effect of the sulfate (SO(4)(2-), surrounded by explicit water molecules) H-bonding to the side chain of Arg236. We find that when sulfate interacts with Arg236, the carboxylate group of Asp237 tends to be protonated, and once Asp237 is protonated, the Fe(iii)Fe(iv) center in X favors the di-oxo bridge (model-I). This would explain that the ENDOR observed RNR-X active site structure is likely to be represented by model-I rather than model-II.

Conformational preferences and cis–trans isomerization of L‐3,4‐dehydroproline residue

The conformational study of N-acetyl-N'-methylamide of L-3,4-dehydroproline (Ac-Dhp-NHMe, the Dhp dipeptide) is carried out using hybrid density functional methods with the self-consistent reaction field method in the gas phase and in solution (chloroform and water). The incorporation of a double bond between C(beta) and C(gamma) into the prolyl ring results in the puckering, backbone population, and barriers to prolyl cis-trans isomerization different from those of the Pro dipeptide. For local minima of the Dhp dipeptide in the gas phase and in water, the C(beta)-C(gamma) bonds become shorter by approximately 0.2 A and the bond angles C(alpha)-C(beta)-C(gamma) and C(beta)-C(gamma)-C(delta) are widened by approximately 8 degrees than those of the Pro dipeptide, and the puckering amplitude is computed to be 0.01-0.07 A, indicating that the 3,4-dehydroprolyl ring is quite less puckered. However, polyproline-like conformations become preferred and the relative stability of the conformation tC with a C(7) intramolecular hydrogen bond decreases as the solvent polarity increases, as found for the Pro dipeptide. The barriers to cis-trans isomerization of the Ac-Dhp peptide bond increase with the increase of solvent polarity and the isomerization is likely to proceed through the clockwise rotation in water, as found for the prolyl peptide bond. The hydrogen bond between the prolyl nitrogen and the following amide N-H group seems to contribute in stabilizing the transition state structures.

Structures and Properties of Nicotinic Acid Dimer

Nicotinic acid dimer was subjected to density functional theory calculations using B3LYP/6-311+G(d,p) basis set. Seven equilibrium isomers were located on the potential energy surface. The most stable structure isomer 1 has a strong N…H—O hydrogen-bonding interaction, and its calculated binding energy is -48.3 kJ·mol-1 corrected with basis set superposition error (BSSE). A normal-mode analysis of the vibrations of the seven isomers was carried out. The charge transfer (CT) and their corresponding second-order interaction energies were studied by nature bond orbital (NBO) analysis. The solvent effects on the geometry of the stablest equilibrium isomer 1 were systematically studied by self-consistent reaction field polarized continuum model (PCM) technique with different dielectric constants of 1.0 (vacuum), 2.247(benzene), 10.36(dichloroethane), 20.7(acetone), 32.63(methanol), and 78.39(water). It was found that the solvent effect would significantly enhance the strength of hydrogen bond as shown by the decrease of the N…H distance. The solvent effect is obvious when e is in 1.0-32.63 and is weak when e exceeds 32.63.

A theoretical thermochemical study of solute-solvent dielectric effects in the displacement of codon-anticodon base pairs

Quantum-chemical solvent effect theories describe the electronic structure of a molecular subsystem embedded in a solvent or other molecular environment. The solvation of biomolecules is important in molecular biology, since numerous processes involve proteins interacting in changing solvent-solute systems. In this theoretical study, we focus on mRNA-tRNA base pairs as a fundamental step in protein synthesis influenced by hydrogen bonding between two antiparallel trinucleotides, namely, the mRNA codon and tRNA anticodon. We use the mean reaction field theories, which describe electrostatic and polarization interactions between solute and solvent in the AAA, UUU, AAG, and UUC triplex sequences optimized in various solvent media such as water, dimethylsulfoxide, methanol, ethanol, and cyclopean using the self-consistent reaction field model. This process depends on either the reaction potential function of the solvent or charge transfer operators that appear in solute-solvent interaction. Because of codon and anticodon biological criteria, we performed nonempirical quantum-mechanical calculations at the BLYP and B3LYP/3-21G, 6-31G, and 6-31G* levels of theory in the gas phase and five solvents at three temperatures. Finally, to obtain more information, we calculated thermochemical parameters to find that the dielectric constant of solvents plays an important role in the displacement of amino acid sequences on codon-anticodon residues in proteins, which can cause some mutations in humans.

An efficient implementation for determining volume polarization in self-consistent reaction field theory

An efficient algorithm of the surface and volume polarization for electrostatics (SVPE) method in self-consistent reaction field (SCRF) theory, denoted by SV(1)PE, has been proposed to simulate direct volume polarization potential with a single layer of point charges outside the solute cavity while the indirect effects of volume polarization on surface polarization are still simulated with multiple layers of point charges. The free energies of solvation calculated using the SV(1)PE algorithm (implemented in GAUSSIAN03) reproduce the corresponding values calculated using the standard SVPE implementation within an error of only approximately 0.1% when the solute cavity is defined by the standard 0.001e/a(0) (3) solute charge isodensity contour. The SV(1)PE results are much less sensitive to the used cavity size in comparison with the well-established surface and simulated volume polarization for electrostatics [SS(V)PE] method which simulates volume polarization through an additional surface charge distribution on the cavity surface. The SCRF calculations using the SV(1)PE method are more efficient than those using the original SVPE method.

Electronic Structure, Molecular Electrostatic Potential, and NMR Chemical Shifts in Cucurbit[n]urils (n = 5−8), Ferrocene, and Their Complexes

Electronic structure and molecular electrostatic potential (MESP) in ferrocene (FC), cucurbit[n]urils (CB[n]) with n = 5-8, and their host-guest complexes are obtained within the framework of density functional theory. MESP topography that is employed to gauge the dimensions of the CB[n] cavity estimates that the cavity height increases from 7.25 to 7.70 A along CB[n] homologue series, whereas the diameter of the CB[8] (8.57 A) cavity is larger than twice that of CB[5] (3.91 A). MESP investigations reveal deeper minima near ureido oxygens in CB[5] along with large electron-rich regions at its portal. A lateral interaction of the guest FC with hydrophilic exterior of the CB[n] portal and its encapsulation within hydrophobic cavity of the host are analyzed. The present calculations suggest that CB[5] does not yield stable complexes in either case. FC interacts laterally with CB[6], and inclusion of the guest occurs, both parallel as well as perpendicular to the CB[n] axis, in the cavity of higher homologue. Self-consistent reaction field studies indicate that, in the presence of water as a solvent, encapsulation of FC in parallel fashion is favored within CB[7] and CB[8] cavities. NMR chemical shifts (delta(H)) of CB[n] protons remain practically unchanged with an increase in the cavity size; however, they are influenced significantly by water. The spectra thus obtained in aqueous solution agree with those observed experimentally. The delta(H) values in FC-CB[n] complexes indicate deshielding of FC protons directed toward portals, while those pointing toward nitrogens exhibit up-shifts in the spectra.

Conformational preferences of N‐methoxycarbonyl proline dipeptide

The conformational study on N-methoxycarbonyl-L-proline-N'-methylamide (Moc-Pro-NHMe, prolylcarbamate) is carried out using ab initio HF and density functional B3LYP methods with the self-consistent reaction field method in the gas phase and in solution (chloroform, acetonitrile, and water). The replacement of the N-acetyl group by the N-methoxycarbonyl group results in the changes in conformational preferences, populations for backbone and prolyl puckering, and barriers to cis-trans isomerization of the prolyl residue in the gas phase and in solution, although there are small changes in the geometry of the prolyl peptide bond and the torsion angles of backbone and prolyl ring. The cis population increases with the increase of solvent polarity, as found for Ac-Pro-NHMe (prolylamide), but it is amplified by 9% in the gas phase and about 17% in solution for prolylcarbamate compared with those for prolylamide. It is found that the cis-trans isomerization for prolylcarbamate proceeds through the clockwise rotation with omega' approximately +120 degrees about the prolyl peptide bond in the gas phase and in solution, as found for prolylamide. However, the rotational barriers to the cis-trans isomerization for prolylcarbamate are calculated to be 3.7-4.7 kcal/mol lower than those of prolylamide in the gas phase and in solution, and are found to be less sensitive to the solvent polarity. The calculated rotational barriers for prolylcarbamate in chloroform and water are in good agreement with the observed values. The shorter hydrogen-bond distance between the prolyl nitrogen and the amide H (H(NHMe)) of the NHMe group, the decrease in electron overlap of the prolyl C-N bond, and the favorable electrostatic interaction between the ester oxygen and the amide H(NHMe) for the transition state seem to play a role in lowering the rotational barrier of prolylcarbamate. The smaller molecular dipole moments of the ground- and transition-state structures for prolylcarbamate in the gas phase and in solution seem to be one of factors to make the rotational barrier less sensitive to the solvent polarity. As the solvent polarity increases (i.e., from the gas phase to chloroform to acetonitrile), the value of DeltaH(tc)(double dagger) decreases and the magnitude of DeltaS(tc)(double dagger) increases for prolylcarbamate, which results in a nearly constant value of the rotational barrier.

Density functional theory and ab-initio computational study of molecular structure, tautomerism, and geometrical isomerism of ethynyl-bridged dipyridinones: In the gas phase and dielectric media

The geometries and relative stabilities for the different isomers and tautomers of ethynyl-bridged dipyridinones were calculated with full geometry optimizations using DFT method. Solvent effects have been analysed using the self-consistent reaction field theory with Onsager and continuum models for three different solvent, CHCl 3, CH 3OH and H 2O. The geometrical parameters of all structures were almost unaffected by the solvent. Except 3a and 3b, all compounds were found to have planar structure in the gas phase and in solutions. For the 3a and 3b tautomers were observed small divergence from planarity. The keto forms were calculated considerably to be more stable than the enol forms in the gas phase and in all solutions. The differences in relative energy values between tautomers were increased in general by the effect of solvent.

Conformational preferences of beta- and gamma-aminated proline analogues.

Quantum mechanical calculations have been used to investigate how the incorporation of an amino group to the Cbeta- or Cgamma-positions of the pyrrolidine ring affects the intrinsic conformational properties of the proline. Specifically, a conformational study of the N-acetyl-N'-methylamide derivatives of four isomers of aminoproline, which differ not only in the beta- or gamma-position of the substituent but also in its cis or trans relative disposition, has been performed. To further understand the role of the intramolecular hydrogen bonds between the backbone carbonyl groups and the amino side group, a conformational study was also performed on the corresponding four analogues of (dimethylamino)proline. In addition, the effects of solvation on aminoproline and (dimethylamino)proline dipeptides have been evaluated using a self-consistent reaction field model, and considering four different solvents (carbon tetrachloride, chloroform, methanol and water). Results indicate that the incorporation of the amino substituent into the pyrrolidine ring affects the conformational properties, with backbone...side chain intramolecular hydrogen bonds detected when it is incorporated in a cis relative disposition. In general, the incorporation of the amino side group tends to stabilize those structures where the peptide bond involving the pyrrolidine nitrogen is arranged in cis. The aminoproline isomer with the substituent attached to the Cgamma-position with a cis relative disposition is the most stable in the gas phase and in chloroform, methanol and water solutions. Replacement of the amino side group by the dimethylamino substituent produces significant changes in the potential energy surfaces of the four investigated (dimethylamino)proline-containing dipeptides. Thus, these changes affect not only the number of minima, which increases considerably, but also the backbone and pseudorotational preferences. In spite of these effects, comparison of the conformational preferences, i.e., the more favored conformers, calculated for different isomers of aminoproline and (dimethylamino)proline dipeptides showed a high degree of consistency for the two families of compounds.

Development of a Finite-Temperature Density Functional Approach to Electrochemical Reactions

We present a computational method to calculate the electronic states of a molecule in an electrochemical environment. The method is based on our recently developed finite-temperature density functional theory approach to calculate the electronic structures at a constant chemical potential. A solvent effect is treated at the level of the extended self-consistent reaction field model, which allows considering a nonequilibrium solvation effect. An exchange-correlation functional with a long-range correction is employed in this calculation, because the functional is adjusted so that the derivative discontinuity of energy with respect to a number of electrons could be satisfied. It has been found that the derivative discontinuity condition plays a crucial role in an electrochemical system. The computational results are presented for a reaction of NO(+) + e(-) <==> NO in chemical equilibrium. Owing to the improvement in the solvation effect and the exchange-correlation functional, the calculated activation free energy is in good agreement with experimental results.

Energetic analyses of chair and boat conformations of maleimide substituted cyclohexane derivatives

An analysis of the conformational preferences of two maleimide substituted cyclohexane derivatives proposed as scaffolds for HIV-1 fusion inhibitors is presented. Hybrid Low Mode-Monte Carlo (1:1) conformational searches using seven different force fields were performed in combination with the GBSA(water) solvent model. Low energy structures identified in this way were subjected to geometry optimization on the B3LYP/6-31G** surface. Solvent effects were included in the quantum calculation using the self-consistent reaction field model for water. Quantum results indicate that the 1,3,5-maleimide functionalized 1,3,5-methyl cyclohexane is more stable in the boat conformation, whereas 1,3,5-maleimide functionalized cyclohexane adopts the expected chair conformation with equatorial arms. None of the force fields studied was able to predict the unexpected preference for the boat conformation of 1,3,5-maleimide functionalized 1,3,5-methyl cyclohexane. Comparison of low energy and experimental structures was also performed.

Theoretical Studies on the Redox Potentials of Fe Dinuclear Complexes as Models for Hydrogenase

Density Functional calculations have been performed at the uB3LYP and uBP86 levels to calculate the one-electron redox potentials for a series of small models based on the diiron hydrogenase enzymes in the presence of acetonitrile (MeCN). The solvation effects in MeCN are incorporated via a self-consistent reaction field (SCRF) using the polarized continuum model (PCM). The calculated redox potentials reproduce the trends in experimental data with an average error of only 0.12 V using the BP86 functional, whereas comparing results with the B3LYP functional require a systematic shift of -0.82 and -0.53 V for oxidation and reduction, respectively. The bonding orbitals and d-electron populations were examined using Mulliken population analysis, and the results were used to rationalize the calculated and observed redox potentials. These studies demonstrate that the redox potential correlates with the empirical spectrochemical series for the ligands, as well as with the amount of electron density donated by the ligand onto the Fe centers.

QM/MM−PBSA Method To Estimate Free Energies for Reactions in Proteins

We have developed a method to estimate free energies of reactions in proteins, called QM/MM-PBSA. It estimates the internal energy of the reactive site by quantum mechanical (QM) calculations, whereas bonded, electrostatic, and van der Waals interactions with the surrounding protein are calculated at the molecular mechanics (MM) level. The electrostatic part of the solvation energy of the reactant and the product is estimated by solving the Poisson-Boltzmann (PB) equation, and the nonpolar part of the solvation energy is estimated from the change in solvent-accessible surface area (SA). Finally, the change in entropy is estimated from the vibrational frequencies. We test this method for five proton-transfer reactions in the active sites of [Ni,Fe] hydrogenase and copper nitrite reductase. We show that QM/MM-PBSA reproduces the results of a strict QM/MM free-energy perturbation method with a mean absolute deviation (MAD) of 8-10 kJ/mol if snapshots from molecular dynamics simulations are used and 4-14 kJ/mol if a single QM/MM structure is used. This is appreciably better than the original QM/MM results or if the QM energies are supplemented with a point-charge model, a self-consistent reaction field, or a PB model of the protein and the solvent, which give MADs of 22-36 kJ/mol for the same test set.

Theoretical investigation of tautomeric equilibrium in ortho-hydroxy phenyl Schiff bases

This Letter presents a study of the tautomeric equilibrium in ortho-hydroxy phenyl Schiff bases. The influence of substitution and solvent (simulated by the self-consistent reaction field model, SCRF) on the energy barrier of the transition state and on proton transfer is investigated. Dependencies of the HOMA and HOSE aromaticity indices on the molecular, transition state, and proton transfer forms were obtained. The state of chelate chain and phenyl ring aromaticity depending on the tautomeric equilibrium is studied.

Continuum Electrostatics for Electronic Structure Calculations in Bulk Amorphous Polymers: Application to Polylactide

The bond rotational energy landscapes of polylactide (PLA) oligomers were estimated using electron density functional theory (DFT) at the B3LYP/6-31G** level, both in vacuo and with a self-consistent reaction field (SCRF) method to simulate the electronic environment within the condensed phase. The SCRF method was evaluated for application to polymeric systems, and we demonstrate the difficulties involved in applying the method to bulk amorphous polymers with specific attention to the selection of the solvent probe radius. In addition, rotational isomeric states (RIS) calculations were performed, showing the effect of accounting for the bulk phase reaction field on the bond rotational energetics and characteristic ratio. We conclude that present methods of accounting for bulk environments in electronic structure calculations are not well suited for use with polymeric systems, and the development of improved methods is needed in this area.

Quenching Reactions of Triplet State Riboflavin by Vitamin C: A Theoretical Investigation

Sir, Vitamin C (ascorbic acid), the water-soluble, smallmolecule antioxidant, is of great biological significance [1, 2]. Previous studies [3, 4] demonstrated that vitamin C can inhibit the photo-oxidative damage caused by riboflavin which can induce Type-I and II photosensitized oxidation mechanisms [5–7]. Considering the fact that many antioxidants can inhibit the riboflavin’s photosensitizing damage through deactivating its triplet state [7–9], it is of significance to investigate the reactions of vitamin C with triplet state riboflavin, which may contribute to the protective effect of vitamin C. In the present study, the quenching mechanisms of triplet state riboflavin by vitamin C were explored by means of density functional theory (DFT) calculations, which have been widely used in investigating both the antioxidant and photosensitization mechanisms of various bioactive compounds [7, 11–14]. The calculation methods are as follows. Firstly, molecular structures of vitamin C (monoanion form in neutral solution) and riboflavin were fully optimized by hybrid functional B3LYP with 6-31G(d,p) Gaussian basis set in vacuo. Then, the lowest triplet excitation energy (ET1) of the two molecules was estimated by time-dependent (TD)DFT with the same basis set in solvent (water). Moreover, as the diffuse functions are essential for treatment of anion and cation radicals, the vertical electron affinities (VEA) and vertical ionization potentials (VIP) of vitamin C and riboflavin were estimated using a combined DFT method labeled as B3LYP/6-31+G(d,p)//B3LYP/6-31G(d,p), which means that B3LYP/6-31+G(d,p) was used to perform a single-point calculation on the basis of B3LYP/631G(d,p)-optimized structures. The O-H bond dissociation enthalpy (BDE) of vitamin C and H-atom affinity (HAA) of riboflavin were calculated by (RO)B3LYP/6311+G(2d,2p)//AM1 method, which takes advantages of accuracy and economy [11]. During the single point calculations, the solvent (water) effect was taken into consideration by employing the self-consistent reaction field (SCRF) method with the polarizable continuum model (PCM) of Tomasi and coworkers [15–17]. All the calculations were accomplished with the Gaussian 03 package of programs [18]. During the photosensitization, riboflavin is initially excited to the singlet state upon irradiation and then may intersystem cross to the relatively long-lived triplet state. Triplet state riboflavin can react with molecular oxygen to photogenerate various reactive oxygen species [5–7] and at the same time, it can be deactivated by vitamin C, theoretically through the following possible pathways. Firstly, triplet state riboflavin (RF) may react with vitamin C (VC) through direct energy transfer (Eq. 1).

Conformational Preferences and Cis−Trans Isomerization of l-Lactic Acid Residue

The conformational study on N-acetyl- N'-methylamide of l-lactic acid (Ac-Lac-NHMe, the Lac dipeptide) is carried out using ab initio HF and density functional methods with the self-consistent reaction field method to explore its backbone conformational preferences and cis-trans isomerization for the depsipeptide with an ester bond in the gas phase and in solution. In the gas phase and in chloroform, the conformation tB with a trans depsipeptide bond is most preferred for the Lac dipeptide, whose backbone torsion angles are phi approximately -150 degrees and psi approximately -5 degrees , juxtaposed to those of the 3 10-helical structure. The larger shift in phi is brought to reduce the repulsion between the two carbonyl carbons of the acetyl and NHMe groups. However, the polyproline II-like tF conformation becomes more populated and the relative stability of conformation tB decreases significantly as the solvent polarity increases. This may be ascribed to weakening a C(5) hydrogen bond between the depsipeptidyl oxygen and the carboxyl amide hydrogen that plays a role in stabilizing the conformation tB in the gas phase and in chloroform. The cis populations about the depsipeptide bond are nearly negligible in the gas phase and in solution. The rotational barriers to the cis-trans isomerization of the depsipeptide bond for the Lac dipeptide are calculated to be about 11 kcal/mol, which is about half of those for the Ala dipeptide, although they increase somewhat with the increase of solvent polarity. The cis-trans isomerization of the depsipeptide bond proceeds through either clockwise or anticlockwise rotations with torsion angles of about +90 degrees or -90 degrees , respectively, in the gas phase and in solution, whereas it has been known that the isomerization proceeds through only the clockwise rotation for alanyl and prolyl peptide bonds. The pertinent distances between the depsipeptidyl oxygen and the carboxyl amide hydrogen can describe the role of this hydrogen bond in stabilizing the transition state structures in the gas phase and in solution.