Radical Stereochemistry: Accounting for Diastereomers in Kinetic Mechanism Development.

Recent work in combustion and atmospheric chemistry has revealed cases in which diastereomers must be distinguished to accurately model a reacting flow. This paper presents an open-source framework for introducing such stereoisomer resolution into a kinetic mechanism. We detail our definitions and algorithms for labeling and enumerating the stereoisomers of a molecule and then generalize our system to describe the transition state (TS) of a reaction. This allows for the stereospecific enumeration of reactants and products while accounting for "fleeting" stereochemistry that is unique to the TS. We also present the AutoMech Chemical Identifier (AMChI), an InChI-like string identifier that accounts for stereocenters omitted by InChI. This identifier is extended to describe the TSs of reactions, providing a universal lookup key for specific reaction channels. The final piece of our methodology is an analytic formula to remove redundancy from a stereoresolved mechanism when its enantiomers exist as a racemic mixture, making it as compact as possible while fully accounting for the differences between diastereomers. In applying our methodology to two subsets of the NUIGMech1.1 mechanism, we find that our approach reduces the extra species added for large-fuel oxidation from 2231 (133%, full expansion) to 694 (41%, nonredundant expansion). We also find that for pyrolysis more than a quarter of the species in the expanded mechanism cannot be properly described by an InChI string, requiring an AMChI string to communicate their identity. Finally, we find that roughly one-quarter of the large-fuel oxidation reactions and one-third of the pyrolysis reactions include fleeting TS stereochemistry, which may have relevant effects on their kinetics.

Adherence to physical activity recommendations and barriers to physical activity participation among adults with type 1 diabetes.

BACKGROUND: Physical activity (PA) is important for those with type 1 diabetes (T1DM); however, accurate information on PA in people with T1DM is limited. AIMS: This study assessed adherence to PA guidelines using both objective and subjective PA measures and evaluated the relationship between accelerometer-measured PA and cardiovascular disease (CVD) risk factors. Barriers to PA were also assessed. METHODS: Using an observational cross-sectional design, PA was measured objectively over 7 days in 72 participants (34 males) using an accelerometer (ActiGraph) and subjectively using the International Physical Activity Questionnaire (IPAQ). Perceived barriers to PA were assessed using the Barriers to Physical Activity in Diabetes (type 1) scale. Multiple linear regression models assessed the influence of PA on HbA1c and CVD risk factors. RESULTS: Mean age ± SD was 40.9 ± 12.9 years, diabetes duration was 18 ± 11.6 years, and HbA1c was 65 ± 14 mmol/mol /8.0 ± 1.3%. Twenty-three (32%) participants exercised according to PA recommendations as measured by an accelerometer. Sixty-nine (97%) participants reported meeting the recommendations as per the IPAQ. Those meeting recommendations (accelerometry) had a lower HbA1c (p = 0.001), BMI (p = 0.032), waist circumference (p = 0.006), and fat mass (p = 0.032) and a greater number of hypoglycaemic events (p = 0.004). Fear of hypoglycaemia was the strongest barrier to PA (mean 3.4 ± 2.0). CONCLUSION: The majority of participants failed to meet PA recommendations. Meeting the recommendations was associated with healthier CVD risk factor profiles. Individuals with T1DM possibly overestimate their PA using self-reported measures and require support and education to safely improve activity levels.

Watching a hydroperoxyalkyl radical (•QOOH) dissociate.

A prototypical hydroperoxyalkyl radical (•QOOH) intermediate, transiently formed in the oxidation of volatile organic compounds, was directly observed through its infrared fingerprint and energy-dependent unimolecular decay to hydroxyl radical and cyclic ether products. Direct time-domain measurements of •QOOH unimolecular dissociation rates over a wide range of energies were found to be in accord with those predicted theoretically using state-of-the-art electronic structure characterizations of the transition state barrier region. Unimolecular decay was enhanced by substantial heavy-atom tunneling involving O-O elongation and C-C-O angle contraction along the reaction pathway. Master equation modeling yielded a fully a priori prediction of the pressure-dependent thermal unimolecular dissociation rates for the •QOOH intermediate-again increased by heavy-atom tunneling-which are required for global models of atmospheric and combustion chemistry.

Substitution Reactions in the Pyrolysis of Acetone Revealed through a Modeling, Experiment, Theory Paradigm.

The development of high-fidelity mechanisms for chemically reactive systems is a challenging process that requires the compilation of rate descriptions for a large and somewhat ill-defined set of reactions. The present unified combination of modeling, experiment, and theory provides a paradigm for improving such mechanism development efforts. Here we combine broadband rotational spectroscopy with detailed chemical modeling based on rate constants obtained from automated ab initio transition state theory-based master equation calculations and high-level thermochemical parametrizations. Broadband rotational spectroscopy offers quantitative and isomer-specific detection by which branching ratios of polar reaction products may be obtained. Using this technique, we observe and characterize products arising from H atom substitution reactions in the flash pyrolysis of acetone (CH3C(O)CH3) at a nominal temperature of 1800 K. The major product observed is ketene (CH2CO). Minor products identified include acetaldehyde (CH3CHO), propyne (CH3CCH), propene (CH2CHCH3), and water (HDO). Literature mechanisms for the pyrolysis of acetone do not adequately describe the minor products. The inclusion of a variety of substitution reactions, with rate constants and thermochemistry obtained from automated ab initio kinetics predictions and Active Thermochemical Tables analyses, demonstrates an important role for such processes. The pathway to acetaldehyde is shown to be a direct result of substitution of acetone's methyl group by a free H atom, while propene formation arises from OH substitution in the enol form of acetone by a free H atom.

Assessing the Viability of the Methylsulfinyl Radical-Ozone Reaction.

Although integral to remote marine atmospheric sulfur chemistry, the reaction between methylsulfinyl radical (CH3 SO) and ozone poses challenges to theoretical treatments. The lone theoretical study on this reaction reported an unphysically large barrier of 66 kcal mol-1 for abstraction of an oxygen atom from O3 by CH3 SO. Herein, we demonstrate that this result stems from improper use of MP2 with a single-reference, unrestricted Hartree-Fock (UHF) wavefunction. We characterized the potential energy surface using density functional theory (DFT), as well as multireference methodologies employing a complete active-space self-consistent field (CASSCF) reference. Our DFT PES shows, in contrast to previous work, that the reaction proceeds by forming an addition adduct [CH3 S(O3 )O] in a deep potential well of 37 kcal mol-1 . An O-O bond of this adduct dissociates via a flat, low barrier of 1 kcal mol-1 to give CH3 SO2 +O2 . The multireference computations show that the initial addition of CH3 SO+O3 is barrierless. These results provide a more physically intuitive and accurate picture of this reaction than the previous theoretical study. In addition, our results imply that the CH3 SO2 formed in this reaction can readily decompose to give SO2 as a major product, in alignment with the literature on CH3 SO reactions.

Sulfurous and sulfonic acids: Predicting the infrared spectrum and setting the surface straight.

Sulfurous acid (H2SO3) is an infamously elusive molecule. Although some theoretical papers have supposed possible roles for it in more complicated systems, it has yet to be experimentally observed. To aid experiment in detecting this molecule, we have examined the H2O + SO2 potential energy surface at the CCSDT(Q)/CBS//CCSD(T)-F12b/cc-pVTZ-F12b level of theory to resolve standing discrepancies in previous reports and predict the gas-phase vibrational spectrum for H2SO3. We find that sulfurous acid has two potentially detectable rotamers, separated by 1.1 kcal mol-1 ΔH0K with a torsional barrier of 1.6 kcal mol-1. The sulfonic acid isomer is only 6.9 kcal mol-1 above the lowest enthalpy sulfurous acid rotamer, but the barrier to form it is 57.2 kcal mol-1. Error in previous reports can be attributed to misidentified stationary points, the use of density functionals that perform poorly for this system, and, most importantly, the basis set sensitivity of sulfur. Using VPT2+K, we determine that the intense S=O stretch fundamental of each species is separated from other intense peaks by at least 25 cm-1, providing a target for identification by infrared spectroscopy.

Large Intermediates in Hydrazine Decomposition: A Theoretical Study of the N3H5 and N4H6 Potential Energy Surfaces.

Large complex formation involved in the thermal decomposition of hydrazine (N2H4) is studied using transition state theory-based theoretical kinetics. A comprehensive analysis of the N3H5 and N4H6 potential energy surfaces was performed at the CCSD(T)-F12a/aug-cc-pVTZ//ωB97x-D3/6-311++G(3df,3pd) level of theory, and pressure-dependent rate coefficients were determined. There are no low-barrier unimolecular decomposition pathways for triazane (n-N3H5), and its formation becomes more significant as the pressure increases; it is the primary product of N2H3 + NH2 below 550, 800, 1150, and 1600 K at 0.1, 1, 10, and 100 bar, respectively. The N4H6 surface has two important entry channels, N2H4 + H2NN and N2H3 + N2H3, each with different primary products. Interestingly, N2H4 + H2NN primarily forms N2H3 + N2H3, while disproportionation of N2H3 + N2H3 predominantly leads to the other N2H2 isomer, HNNH. Stabilized tetrazane (n-N4H6) formation from N2H3 + N2H3 becomes significant only at relatively high pressures and low temperatures because of fall-off back into N2H3 + N2H3. Pressure-dependent rate coefficients for all considered reactions as well as thermodynamic properties of triazane and tetrazane, which should be considered for kinetic modeling of chemical processes involving nitrogen- and hydrogen-containing species, are reported.

tert-Butyl peroxy radical: ground and first excited state energetics and fundamental frequencies.

Alkylperoxy radicals (RO2˙) are key intermediates in combustion and atmospheric oxidation processes. As such, reliable detection and monitoring of these radicals can provide a wealth of information about the underlying chemistry. The tert-butyl peroxy radical is the archetypal tertiary peroxy radical, yet its vibrational spectroscopy is largely unexplored. To aid in future experimental investigations, we have performed high-level theoretical studies of the fundamental vibrational frequencies of the ground- and first excited states. A conformer search on both electronic surfaces reveals single minimum-energy structures. We predict an Ã2A' ← X[combining tilde]2A'' adiabatic excitation energy of 7738 cm-1via focal point analysis, approximating the CCSDT(Q)/CBS level of theory. This excitation energy agrees to within 17 cm-1 of the most accurate experimental measurement. We compute CCSD(T) fundamental vibrational frequencies via second-order vibrational perturbation theory (VPT2), using a hybrid force field in which the quadratic (cubic/quartic) force constants are evaluated with the ANO1 (ANO0) basis set. Anharmonic resonance polyads are treated with the VPT2 + K effective Hamiltonian approach. Among the predicted fundamental frequencies, the ground state O-O stretch, excited state O-O stretch, and excited state C-O-O bend fundamentals are predicted at 1138, 959, and 490 cm-1, respectively. Basis set sensitivity is found to be particularly great for the O-O stretches, similar to what has already been noted in smaller, unbranched peroxy radicals. Exempting these O-O stretches, agreement with the available experimental fundamentals is generally good (±10 cm-1).

Noncovalent Interactions between Molecular Hydrogen and the Alkali Fluorides: H-H···F-M (M = Li, Na, K, Rb, Cs). High Level Theoretical Predictions and SAPT Analysis.

Various types of hydrogen bonds have been recognized during the past century. In this research, a new type of noncovalent interaction, the dipole-induced hydrogen bond formed between a hydrogen molecule and an alkali halide, H-H···F-M, is studied. Proposed by Zhang and co-workers ( Phys. Chem. Chem. Phys. 2015, 17, 20361), these systems are extensively investigated initially using the "gold standard" CCSD(T) method in conjunction with augmented correlation-consistent polarized core-valence basis sets up to quadruple-ζ. The full triple excitations CCSDT method has been used to further refine the energies. Several properties including geometries, bond energies, vibrarional frequencies, charge distributions, and dipole moments have been reported. The earlier Zhang research considered only the linear H-H···F-M structures. However, we find these linear stationary points to be separated by very small barriers from the much lower lying bent C s structures. The CCSDT/aug-cc-pCVQZ(-PP) method predicts the dissociation energies for bent H-H···F-M (M = Li, Na, K, Rb, Cs) are 2.76, 2.96, 3.00, 2.89, and 2.49 kcal mol-1, respectively, suggesting that the H···F hydrogen bond becomes gradually stronger when alkali metal M goes down the periodic table from Li to K but becomes slightly weaker for Rb and even more for Cs. This Li < Na < K > Rb > Cs order is consistent with that for the dipole moments for the isolated MF (M = Li, Na, K, Rb, Cs) diatomics. Symmetry adapted perturbation theory (SAPT) is used to understand these unusual noncovalent interactions.

High-level theoretical characterization of the vinoxy radical (•CH2CHO) + O2 reaction.

Numerous processes in atmospheric and combustion chemistry produce the vinoxy radical (•CH2CHO). To understand the fate of this radical and to provide reliable energies needed for kinetic modeling of such processes, we have examined its reaction with O2 using highly reliable theoretical methods. Utilizing the focal point approach, the energetics of this reaction and subsequent reactions were obtained using coupled-cluster theory with single, double, and perturbative triple excitations [CCSD(T)] extrapolated to the complete basis set limit. These extrapolated energies were appended with several corrections including a treatment of full triples and connected quadruple excitations, i.e., CCSDT(Q). In addition, this study models the initial vinoxy radical + O2 reaction for the first time with multireference methods. We predict a barrier for this reaction of approximately 0.4 kcal mol-1. This result agrees with experimental findings but is in disagreement with previous theoretical studies. The vinoxy radical + O2 reaction produces a 2-oxoethylperoxy radical which can undergo a number of unimolecular reactions. Abstraction of a ß-hydrogen (a 1,4-hydrogen shift) and dissociation back to reactants are predicted to be competitive to each other due to their similar barriers of 21.2 and 22.3 kcal mol-1, respectively. The minimum-energy ß-hydrogen abstraction pathway produces a hydroperoxy radical (QOOH) that eventually decomposes to formaldehyde, CO, and •OH. Two other unimolecular reactions of the peroxy radical are α-hydrogen abstraction (38.7 kcal mol-1 barrier) and HO2• elimination (43.5 kcal mol-1 barrier). These pathways lead to glyoxal + •OH and ketene + HO2• formation, respectively, but they are expected to be uncompetitive due to their high barriers.

Re-examining ammonia addition to the Criegee intermediate: converging to chemical accuracy.

Stabilized Criegee intermediates (SCI) are formed during the ozonolysis of unsaturated hydrocarbons and have been implicated in the formation of hydroxyl radicals and aerosols. Previous theoretical research [S. Jørgenson and A. Gross, J. Phys. Chem. A, 2009, 113, 10284-10290] computed the rate constants for addition of ammonia to simple SCIs, but reported a wide distribution of quantum chemical energies, depending on the basis set used. We report optimized geometries for these reactions at the CCSD(T)/ANO2 and CCSD(T)/ANO1 levels, and CCSD(T)/CBS energies with perturbative quadruples corrections. We find the inclusion of perturbative quadruples corrections elevates the energy of the transition state by 0.76-0.88 kcal mol-1 relative to the reactants, which qualitatively changes the reaction surface. We calculate rate constants and find that Jørgenson and Gross previously overestimated the rate constants for ammonia addition to SCIs, but were within an order of magnitude. This supports the previous conclusion of Vereecken et al. [L. Vereecken, H. Harder and A. Novelli, Phys. Chem. Chem. Phys., 2012, 14, 14682-14695] that ammonia addition to SCIs is a negligible sink of Criegee intermediates.

Alkali-Metal Trihalides: M+X3- Ion Pair or MX-X2 Complex?

The alkali-metal trihalides MX3 (M = Li, Na, K, Rb, and Cs; X = Cl, Br, and I) are systematically studied using coupled-cluster methods. Benchmarks using CCSD(T) against diatomic experimental results suggest satisfactory performance for the weighted core-valence basis sets (new basis sets for K, Rb, and Cs) selected for predicting reliable structures and harmonic vibrational frequencies. An isomer search using the B3LYP functional yields a planar, yet asymmetric T-shaped C s structure as the global minimum for all MX3 species. Much higher level CCSD(T) computations show a moderate to strong distortion of the X3- anion by the M+ cation in the respective equilibrium geometries. Most obviously, for LiCl3, the two Cl-Cl distances are separated by 0.786 Å. Even for CsI3, the structure least distorted from the M+X3- model, the two I-I distances differ by 0.243 Å. It does not take much energy to distort the parent anions along an antisymmetric stretch, so this is no surprise. The normal modes of vibration of the MX3 molecules are in better agreement with matrix isolation experiments than previous calculations. And these normal modes reveal that, instead of the well-established antisymmetric and symmetric stretches of the "free" X3- anions, relatively localized and mutually perturbed X-X and M-X stretches are calculated. The suggestion emerges that the MX3 system may be alternatively described as an MX-X2 complex rather than the M+X3- ion pair. This perspective is supported by bonding analyses showing low electron densities at the bond critical points and natural bond orders between the MX and X2 moieties. The thermochemistry of fragmentations of MX3 to MX + X2 versus M+ + X3- also supports the alternative viewpoint of the bonding in this class of molecules.

Communication: The Al + CO2 → AlO + CO reaction: Experiment vs. theory.

Based on their highly sophisticated crossed-beam experimental studies of the Al + CO2 → AlO + CO reaction, Honma and Hirata have directly challenged the results of earlier theoretical studies of this system. We report high level theoretical studies of this system. It is shown that, consistent with Honma-Hirata experimental conclusions, the previous theoretical prediction of a substantial barrier height for this reaction was incorrect. However, for the structures of the possible intermediates, in agreement with the 1992 theoretical study of Sakai, we find striking disagreement with the experimental conclusion that the O-C-O moiety is nearly linear. The energies of the three entrance channel intermediates lie 14.4, 15.2, and 16.4 kcal mol-1 below separated Al + CO2.

C-H···O Hydrogen Bonding. The Prototypical Methane-Formaldehyde System: A Critical Assessment.

Distinguishing the functionality of C-H···O hydrogen bonds (HBs) remains challenging, because their properties are difficult to quantify reliably. Herein, we present a study of the model methane-formaldehyde complex (MFC). Six stationary points on the MFC potential energy surface (PES) were obtained at the CCSD(T)/ANO2 level. The CCSDT(Q)/CBS interaction energies of the conformers range from only -1.12 kcal mol-1 to -0.33 kcal mol-1, denoting a very flat PES. Notably, only the lowest energy stationary point (MFC1) corresponds to a genuine minimum, whereas all other stationary points-including the previously studied ideal case of ae(C-H···O) = 180°-exhibit some degree of freedom that leads to MFC1. Despite the flat PES, we clearly see that the HB properties of MFC1 align with those of the prototypical water dimer O-H···O HB. Each HB property generally becomes less prominent in the higher-energy conformers. Only the MFC1 conformer prominently exhibits (1) elongated C-H donor bonds, (2) attractive C-H···O═C interactions, (3) n(O) → σ*(C-H) hyperconjugation, (4) critical points in the electron density from Bader's method and from the noncovalent interactions method, (5) positively charged donor hydrogen, and (6) downfield NMR chemical shifts and nonzero 2J(CM-HM···OF) coupling constants. Based on this research, some issues merit further study. The flat PES hinders reliable determinations of the HB-induced shifts of the C-H stretches; a similarly difficult challenge is observed for the experiment. The role of charge transfer in HBs remains an intriguing open question, although our BLW and NBO computations suggest that it is relevant to the C-H···O HB geometries. These issues notwithstanding, the prominence of the HB properties in MFC1 serves as clear evidence that the MFC is predominantly bound by a C-H···O HB.

The fate of the tert-butyl radical in low-temperature autoignition reactions.

Alkyl combustion models depend on kinetic parameters derived from reliable experimental or theoretical energetics that are often unavailable for larger species. To this end, we have performed a comprehensive investigation of the tert-butyl radical (R• in this paper) autoignition pathways. CCSD(T)/ANO0 geometries and harmonic vibrational frequencies were obtained for key stationary points for the R• + O2 and QOOH + O2 mechanisms. Relative energies were computed to chemical accuracy (±1 kcal mol-1) via extrapolation of RCCSD(T) energies to the complete basis-set limit, or usage of RCCSD(T)-F12 methods. At 0 K, the minimum energy R• + O2 pathway involves direct elimination of HO2∙ (30.3 kcal mol-1 barrier) from the tert-butyl peroxy radical (ROO•) to give isobutene. This pathway lies well below the competing QOOH-forming intramolecular hydrogen abstraction pathway (36.2 kcal mol-1 barrier) and ROO• dissociation (35.9 kcal mol-1 barrier). The most favorable decomposition channel for QOOH radicals leads to isobutene oxide (12.0 kcal mol-1 barrier) over isobutene (18.6 kcal mol-1 barrier). For the QOOH + O2 pathways, we studied the transition states and initial products along three pathways: (1) α-hydrogen abstraction (42.0 kcal mol-1 barrier), (2) γ-hydrogen abstraction (27.0 kcal mol-1 barrier), and (3) hydrogen transfer to the peroxy moiety (24.4 kcal mol-1 barrier). The barrier is an extensive modification to the previous 18.7 kcal mol-1 value and warrants further study. However, it is still likely that the lowest energy QOOH + O2 pathway corresponds to pathway (3). We found significant spin contamination and/or multireference character in multiple stationary points, especially for transition states stemming from QOOH. Lastly, we provide evidence for an A∼-X∼ surface crossing at a Cs-symmetric, intramolecular hydrogen abstraction structure.

Liquid hot NAGMA cooled to 0.4 K: benchmark thermochemistry of a gas-phase peptide.

Vibrational spectroscopy and helium nanodroplet isolation are used to determine the gas-phase thermochemistry for isomerization between conformations of the model dipeptide, N-acetylglycine methylamide (NAGMA). A two-stage oven source is implemented to produce a gas-phase equilibrium distribution of NAGMA conformers, which is preserved when individual molecules are captured and cooled to 0.4 K by He nanodroplets. With polarization spectroscopy, the IR spectrum in the NH stretch region is assigned to a mixture of two conformers having intramolecular hydrogen bonds composed of either five- or seven-membered rings, C5 and C7, respectively. The C5 to C7 interconversion enthalpy and entropy, obtained from a van't Hoff analysis, are -4.52 ± 0.12 kJ/mol and -12.4 ± 0.2 J/(mol · K), respectively. The experimental thermochemistry is compared to high-level electronic structure theory computations.

Atomic force microscopy characterization and lithography of Cu-ligated mercaptoalkanoic acid "molecular ruler" multilayers.

Hybrid chemical patterning strategies that combine the sophistication of lithography with the intrinsic precision of molecular self-assembly are of broad interest for applications including nanoelectronics and bioactive surfaces. This approach is exemplified by the molecular-ruler process where the sequential deposition of mercaptoalkanoic acid molecules and coordinated metal ions is integrated with conventional lithographic techniques to fabricate registered, nanometer-scale spacings. Herein, we illustrate the capabilities of atomic force microscopy characterization and lithography to investigate the morphology, quality, and local thickness of Cu-ligated mercaptohexadecanoic acid multilayers on Au{111} substrates. These multilayers are a key component utilized in the molecular-ruler process. The rich and varied topographic features of each layer are investigated via contact-mode atomic force microscopy. Using nanoshaving, an atomic force microscopy lithographic strategy that reveals the underlying Au{111} substrate via tip-induced desorption of a molecular film, the local thicknesses of these multilayers are ascertained; these thicknesses are consistent with the anticipated heights for Cu-ligated mercaptohexadecanoic acid multilayers as well as previous ensemble surface analytical measurements. By regulating the force set point utilized during nanoshaving, the upper layer of a Cu-ligated mercaptohexadecanoic acid bilayer is removed, revealing the carboxyl moiety of the lower mercaptohexadecanoic acid layer. This selective nanoshaving demonstrates a simple and practical means to generate three-dimensional multilayers and to reveal buried chemical functionalities within metal-ligated multilayers.

Streptococcal hyaluronate lyase reveals the presence of a structurally significant C-H⋠⋠⋠O hydrogen bond.

Carbon-donated hydrogen bonds (CDHBs) are weak forms of hydrogen bonding (0.5-1.0 kcal mol(-1) ) that are difficult to detect, and thus their roles in the structure and functionality of chemical systems often go unrecognized. Utilizing a computational approach, the existence of a structurally significant CDHB in the medically relevant protein Streptococcus pneumoniae hyaluronate lyase (SpnHL) is affirmed. The structure of a tetrapeptide fragment model containing the CDHB was optimized with second-order perturbation theory. From this, a CDHB with bond distance and angle consistent with previously discovered CDHBs and comparable to neighboring traditional HBs in the fragment model was found. The CDHB competes with another donor T253 OH, whereby the two alternate in strength between protein conformations, imbuing αHelix 3 appreciable flexibility. The CDHB seems to exist in spite of torsional and steric strain on the donor methyl group. It is postulated that the CDHB could aid in either counteracting the macrodipole of αHelix 3 or protecting the A249 CO from destabilizing interactions with the adjacent solvent. Employing the energy gradients from the optimization, the torque generated by the fragment model was computed, which accurately predicts the direction of rotation of αHelix 3 observed from experiment. A strongly correlated motion between αHelix 3 and αHelices 2, 4, and 5 was noted, which the interactions of the fragment model help drive by generating a torque much larger than necessary to rotate just αHelix 3. Considering these results, we conclude that CDHBs should be considered as possible beneficial components of chemical and biological phenomena.

Therapeutic potential of dipeptidyl peptidase-IV inhibitors in patients with diabetes mellitus.

Dipeptidyl peptidase-IV (DPP-IV) inhibitors are a new class of oral antidiabetic agents for the treatment of patients with type 2 diabetes. Inhibition of the enzyme DPP-IV results in increased activity of glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic peptide (GIP), the incretin hormones. Through the action of GLP-1 and GIP, DPP-IV inhibitors improve preprandial and postprandial glucose by enhancing insulin secretion and reducing postprandial concentrations of glucagon. This review examines the background, current evidence, and future therapeutic potential of this novel class of drug.