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Scott Gronert

Publications and source records attributed to Scott Gronert.

17 recordsLinked to original sources
PubMed2006

Evidence that alkyl substitution provides little stabilization to radicals: the C-C bond test and the nonbonded interaction contradiction.

Although the C-H bond dissociation energies of alkanes have been widely employed as measures of radical stability, it is shown here that the assumptions needed for that conclusion are incompatible with experimental and computational data related to C-C bond dissociation energies. Calculations at the QCISD(T)/6-311+G(d,p) level on model systems show that 1,3 nonbonded interactions in alkanes are repulsive, whereas the conventional radical stabilization analysis of bond dissociation energies requires that they become more attractive with increasing steric bulk. This result puts a severe limit on the role that radical stabilization can play and indicates that another factor must be responsible for the observed variation in the C-H bond dissociation energies of alkanes.

Journal Article↗
PubMed2006

Primary semiclassical kinetic hydrogen isotope effects in identity carbon-to-carbon proton- and hydride-transfer reactions, an ab initio and DFT computational study.

Enthalpies of activation, transition state (ts) geometries, and primary semiclassical (without tunneling) kinetic isotope effects (KIEs) have been calculated for eleven bimolecular identity proton-transfer reactions, four intramolecular proton transfers, four nonidentity proton-transfer reactions, eleven identity hydride transfers, and two 1,2-intramolecular hydride shifts at the HF/6-311+G, MP2/6-311+G, and B3LYP/6-311++G levels. We find the KIEs to be systematically smaller for hydride transfers than for proton transfers. This outcome is not the result of "bent" transition states, although extreme bending can lower the KIE. Rather, it is a consequence of generally greater total bonding in a hydride-transfer ts than in a proton-transfer ts, most prominently manifested as a reduced contribution from the zero-point vibrational energy difference between reactant and transition states (the DeltaZPVE factor) for hydride transfers relative to proton transfers. This and other differences between proton and hydride transfers are rationalized by modeling the central .C...H...C unit of a proton-transfer ts as a 4-electron, 3-center (4-e 3-c) system and the same unit of a hydride-transfer ts as a 2-e 3-c system. Inclusion of tunneling is most likely to magnify the observed differences between proton-transfer and hydride-transfer KIEs, leaving our qualitative conclusions unchanged.

Journal Article↗
PubMed2006

Identification of specific protein carbonylation sites in model oxidations of human serum albumin.

Human serum albumin (HSA) was subjected to oxidative stress and the locations of the resulting protein carbonyls were determined using mass spectrometry in conjunction with a hydrazide labeling scheme. To model oxidative stress, HSA samples were subjected to metal-catalyzed oxidation (MCO) conditions or treated with hypochlorous acid (HOCl). Oxidation led to the conversion of lysine residues to 2-aminoadipic semi-aldehyde residues, which were subsequently labeled with biotin hydrazide. Analysis of the tryptic peptides from the samples indicates that the oxidations are highly selective. Under MCO conditions, only two of the 59 lysine residues appeared to be modified (Lys-97 and Lys-186). With HOCl, five different lysine modification sites were identified (Lys-130, Lys-257, Lys-438, Lys-499, and Lys-598). These results strongly suggest that the preferred site of modification is dependent on the nature of the oxidant and that the process relies on specific structural motifs in the protein to direct the oxidation. The high selectivity seen here provides insights into the factors that in vivo drive the selective carbonylation of specific proteins in systems under oxidative stress.

Binding Sites↗
PubMed2006

An alternative interpretation of the C-H bond strengths of alkanes.

A new model based on 1,3 repulsive steric interactions (geminal repulsion) is proposed for explaining the variation in the C-H bond strengths of the alkanes. The model builds from the assumption that 1,3 repulsive interactions are the major factor in determining the stability of a C-C or C-H bond in an alkane. From this simple premise, the model successfully reproduces the effect of branching on the stability of alkanes, alkyl radicals, and alkenes. The results suggest that geminal repulsion can provide a simple, unified explanation for these fundamental stability trends. Although previous explanations have been widely accepted, it is shown that the theoretical support for them is relatively shallow and that the current hyperconjugative stabilization model is inconsistent with several experimental and computational results concerning alkyl radicals. In contrast, an explanation based on geminal repulsion provides a general conceptual framework for rationalizing each of these stability trends and is based on a physical effect that is known to play a role in the stability of alkanes and related species.

Journal Article↗
PubMed2005

Manipulating the fragmentation patterns of phosphopeptides via gas-phase boron derivatization: determining phosphorylation sites in peptides with multiple serines.

Trivalent boron species readily react with protonated phosphopeptides to give addition products with the loss of boron ligands. In the present study, trimethoxyborane (TMB), diisopropoxymethylborane (DIPM), and diethylmethoxyborane (DEMB) were allowed to react with four phosphopeptides, VsSF, LSsF, LsGASA, and VSGAsA (lower-case s indicates phosphoserine). Each of the phosphopeptides contains one serine that is phosphorylated and one that is not. Under collision-activated dissociation (CAD) conditions, the boron-derivatized peptides give fragmentation patterns that differ significantly from that of the protonated phosphopeptide. The patterns vary, depending on the number of labile (i.e., alkoxy) ligands on the boron. In general, boron derivatization increases the yield of phosphate-containing sequence ions, but dramatic effects are only seen with certain reagent/peptide combinations. However, the suite of reagents provides a means of altering and increasing the information content of phosphopeptide CAD spectra.

Algorithms↗
PubMed2005

Identity hydride-ion transfer from C-H donors to C acceptor sites. Enthalpies of hydride addition and enthalpies of activation. Comparison with C...H...C proton transfer. An ab initio study.

Enthalpies of addition of hydride ion to eleven carbonyl acceptors (X-CHO), two conjugate addition sites (X-CH=CH2; X = CHO, NO2), eight carbenium ion acceptors, fulvene, borane, and SiH3(+) were calculated at the MP2/6-311+G level. Correlation between calculated and experimental enthalpies of addition of hydride ion is excellent. Transition states (ts) for the identity hydride transfers between the acceptors and their corresponding hydride adducts (hydride donors) were also calculated. The carbonyl and fulvene reactions have transition states with one imaginary frequency: the hydrogen transfer coordinate. The carbenium ions, borane, and SiH3(+) gave not transition states but stable compounds upon addition of the hydride donor. Computational differences between these hydride transfers and previously reported proton transfers include shorter partial C...H bonds and a tendency toward bent C...H...C angles for the hydride transfer ts and addition compound structures, particularly when a bent geometry improves interactions elsewhere in the structure. These and other differences are explained by modeling the hydride transfer ts and addition compounds as two-electron, three-center systems involving the transfer termini and the shared hydrogen but the proton transfer ts structures as four-electron, three-center systems. Charge and geometry measures suggest transition states in which these features change synchronously, again in contrast to many proton transfer reactions. For the X-CHO set, polar effects dominate enthalpies of hydride addition, with resonance effects also important for resonance donors; these preferentially stabilize the acceptor, reducing its hydride ion affinity. Activation enthalpies are dominated by resonance stabilization of the acceptors, greatly attenuated in the transition states.

Journal Article↗
PubMed2005

Zwitterion formation in gas-phase cyclodextrin complexes.

Protonated complexes of amino acids and underivatized beta-cyclodextrin, produced by electrospray ionization and trapped in the Fourier transform mass spectrometer, undergo formation of ternary complexes when reacted with alkyl amine. Based on the reactivities of the protonated amino acid complexes with alkylamines, the reactivities of the corresponding amino acid esters, and partially derivatized beta-cyclodextrin hosts, we conclude that the ternary complexes are salt-bridge zwitterionic species composed of amino acid zwitterions and protonated alkylamine all interacting with the hydroxyl groups on the narrow rim of the cyclodextrin. Molecular modeling calculations and experimental results suggest that the interactions of the amino acids with the rims contribute greatly to the formation of the zwitterionic species.

Amino Acids↗
PubMed2004

Leaving group effects in gas-phase substitutions and eliminations.

Using a methodology recently developed for studying the product distributions of gas-phase S(N)2 and E2 reactions, the effect of the leaving group on the reaction rate and branching ratio was investigated. Using a dianion as the nucleophile, reactions with a series of alkyl bromides, iodides, and trifluoroacetates were examined. The alkyl groups in the study are ethyl, n-propyl, n-butyl, isobutyl, isopropyl, sec-butyl, and tert-butyl. The data indicate that leaving group abilities are directly related to the exothermicities of the reaction processes in both the gas phase and the condensed phase. Gas-phase data give a reactivity order of iodide > trifluoroacetate > bromide for S(N)2 and E2 reactions. Previous condensed phase data indicate a reactivity order of iodide > bromide > trifluoroacetate for substitution reactions; however, the basicities of bromide and trifluoroacetate are reversed in the condensed phase so this reactivity pattern does reflect the relative reaction exothermicities. Aside from this variation, the gas-phase data parallel condensed phase data indicating that the substituent effects are rooted in the nature of the alkyl substrate rather than in differences in solvation. The experimental data are supported by calculations at the MP2/6-311+G(d,p)//MP2/6-31+(d) level.

Journal Article↗
PubMed2004

Modest catalysis of the decarboxylation of orotate by hydrogen bonding: a theoretical model for orotidine- 5' -monophosphate decarboxylase.

As a model for interactions present in the active site of orotidine-5'-monophosphate decarboxylase (ODCase), the effect of hydrogen bonds to the carbonyl groups (O-2 and O-4) of orotic acid and its decarboxylation product was probed with ab initio calculations. We have found that the transition state/carbanion intermediate is a better proton receptor and therefore, the hydrogen bonds can be a modest source of catalysis. Comparison of the calculated data with results from site-directed mutagenesis provides some insights into the polarity of the active site.

Catalysis↗
PubMed2004

Stereoselectivity in the collision-activated reactions of gas phase salt complexes.

The collision-activated dissociations (CAD) of gas phase salt complexes composed of chiral ions were studied in a quadrupole ion trap mass spectrometer. Because both partners in the salt are chiral, diastereomeric complexes can be formed (e.g., RR, RS). Two general types of complexes were investigated. In the first, the complex was composed of deprotonated binaphthol and a chiral bis-tetraalkylammonium dication. CAD of these complexes leads to the transfer of a proton or an alkyl cation to the binaphtholate leading to a singly-charged tetraalkylammonium cation. During CAD, diastereomeric complexes give significantly different product distributions indicating reasonable stereoselectivity in the process. In the second system, the complexes involved a peptide dianion and a chiral tetraalkylammonium cation. These systems may be viewed as very simple models for the interactions of peptides/proteins with small chiral molecules. Again, stereoselectivity was evident during CAD, but the extent was dependent on the nature of the peptide and not observable in some cases. To better understand the structural features needed to achieve stereoselectivity in gas phase salt complexes, representative transition states were modeled computationally. The results suggest that it is critical for the asymmetry of the nucleophile (i.e., anion) to be well represented in the vicinity of its reactive center.

Alanine↗
PubMed2003

Identity proton-transfer reactions from C-H, N-H, and O-H acids. An ab initio, DFT, and CPCM-B3LYP aqueous solvent model study.

Identity proton-transfer reactions between 21 acids, Y-X-H, and their conjugate bases, (-)X-Y, were studied according to the reaction scheme, Y-X-H + (-)X-Y --> (Y-X-H...(-)X-Y)(cx) --> [Y-X...H...X-Y](ts) --> (Y-X..H-X-Y)(cx) --> Y-X(-) + H-X-Y, where cx indicates an ion-molecule complex and ts indicates the proton-transfer transition state. All species were optimized at the MP2/6-311+G level, and these geometries were used for single-point calculations by other methods: coupled-cluster, DFT (gas phase), and a polarizable continuum aqueous solvent model (COSMO). All methods gave enthalpies of deprotonation which correlate well with experimental measurements of deltaH(ACID) (gas) or pK(a) (aq). Calculated gas-phase enthalpies of deprotonation (deltaH(ACID)) and enthalpies of activation (deltaH(#)) are poorly correlated except for small, carefully selected sets. This result stands in contrast to the many aqueous phase Brönsted correlations of kinetic and equilibrium acid strength. On the other hand, gas-phase enthalpies of complexation and deltaH(#) are well correlated, indicating that factors which stabilize the transition state are at work in the bimolecular ion-molecule complex although to a smaller degree. We infer that intermoiety electrostatic and other interactions, similar within the complex and the transition state, but absent in the separated reactants (products), cause the lack of correlation between deltaH(ACID) and the other two quantities. Such differences are strongly attenuated in water because reactants and products do interact with polar/polarizable matter (the solvent) if not with each other. Charge distributions (NPA) were computed, allowing calculation of Bernasconi's "transition state imbalance parameter". Such measures provide intuitively satisfactory trends, but only if the reaction termini, X, are kept the same. As X is made more electronegative, the magnitude of the apparent imbalance increases, a result of greater negative charge on X in the transition state. This result gives additional support for the importance of the ion-triplet structure, [YX(-)...H(+)...(-)XY], to the stability of the transition state. Additional qualitative support for this conclusion is provided by the inverse relationship between the activation barrier and the charge on the in-flight hydrogen in the transition state, and by the dominance of polar over resonance substituent effects on the stability of the transition state. Calculations also show that the "nitroalkane anomaly", well established in solution, does not exist in the gas phase. The COSMO model partly reproduces this anomaly and performs adequately except when strong, specific intermolecular forces such as hydrogen bonding between solvent and anions are important.

Journal Article↗
PubMed2003

Catalysis of decarboxylation by an adjacent negative charge: a theoretical approach.

We have calculated the rate acceleration in decarboxylation reactions that can be accomplished by charge-charge repulsion between the substrate carboxylate and an adjacent negative charge in media of various dielectric constants. It has been shown that a full negative charge or surrounding partial negative charges will have the same effect. It is concluded that the rate of decarboxylation could be greatly accelerated by the presence of a negative charge nearby. For example, in media with dielectric constants from 5.62 to 20.7, a 10(8)-fold rate acceleration could be achieved by a negative charge placed 3.77 A away from the substrate carboxylate group. However, pK(a) perturbation on two carboxylate groups at close proximity may limit the extent of catalysis. It should also be noted that the extent of catalysis does not change much when the dielectric constant varies from 5.62 to 20.7.

Acetic Acid↗
PubMed2003

Gas phase studies of the competition between substitution and elimination reactions.

Gas phase studies allow for the examination of organic reaction mechanisms in the absence of solvation effects and therefore probe the intrinsic reactivity of the reaction partners. The competition between substitution and elimination reactions has been a topic of interest for decades, but it has been difficult to examine in the gas phase because both pathways generally lead to the same ionic product and cannot be distinguished by mass spectrometry. By using dianions as nucleophiles, the reactions produce two ionic products, one of which identifies the mechanism. With this approach, we have examined a variety of substituent effects on the gas phase competition between substitution and elimination. In addition, we have found that similar processes occur during collisional activation of salt complexes that contain a dianion and a tetraalkylammonium cation. Overall, the results show that the gas phase studies probe the same fundamental features found in the condensed phase and provide valuable insights into reaction mechanisms.

Journal Article↗
PubMed2002

Gas phase reactions of trimethyl borate with phosphates and their non-covalent complexes.

Using a quadrupole ion trap mass spectrometer, trimethyl borate was allowed to react with dihydrogen phosphate, deprotonated O-phosphoserine, and a set of hydrogen bonded complexes involving dihydrogen phosphate and neutral acids (phosphoric acid, acetic acid, serine, and O-phosphoserine). The reactions show a consistent pattern in which the initial attack leads to addition with the loss of one or two CH3OH molecules. Collision-activated dissociation (CAD) experiments on the reaction products generally lead to the loss of an additional CH3OH molecule. In no case is a partner from the original hydrogen-bonded complex lost. The results indicate that the reactions lead to structures where the phosphate and its complex partner are covalently bound to the boron. For each of the reactions, rate constants were determined. In the course of CAD experiments (up to MS5), several novel borophosphate structures were identified. The work is supported by ab initio calculations on selected species.

Borates↗
PubMed1997

Theoretical Studies of Eliminations. 6. The Regiochemistry and Stereochemistry of the Gas-Phase Reactions of 3-Halocyclohexenes with Fluoride. An ab Initio Study.

The gas phase reactions of fluoride with 3-chlorocyclohexene and 3-fluorocyclohexene have been investigated with ab initio calculations up to the MP2/6-31+G level. Transition states were located for 1,4-eliminations and 1,2-eliminations as well as S(N)2 and S(N)2' substitutions. For each reaction, a variety of stereochemical outcomes was explored. For both systems, the preferred pathway is an anti 1,4-elimination, but syn 1,4-eliminations and anti 1,2 eliminations have transition states that are nearly as stable. The two modes of substitution (S(N)2 and S(N)2') have similar barriers, but are much less favorable than elimination. The results are compared to recent experimental studies of related systems.

Journal Article↗
PubMedDate not supplied

Quadrupole ion trap studies of fundamental organic reactions.

Over the past several decades, quadrupole ion traps have become important instruments in the study of gas phase ion/molecule reactions. As a part of this work, they have been employed in a number of studies focused on fundamental organic reaction mechanisms. In this review, the general features and limitations of quadrupole ion traps are discussed followed by a description of representative ion trap studies of organic reaction mechanisms such as substitution, elimination, and acyl transfer reactions.

Journal Article↗