Experimental tests of reaction rate theory: Mu+H2 and Mu+D2

Copyright @ 1987 American Institute of Physics.Bimolecular rate constants for the thermal chemical reactions of muonium (Mu) with hydrogen and deuterium—Mu+H2→MuH+H and Mu+D2→MuD+D—over the temperature range 473–843 K are reported. The Arrhenius parameters and 1σ uncertainties for the H2 reaction are log A (cm3 molecule-1 s-1)=-9.605±0.074 and Ea =13.29±0.22 kcal mol-1, while for D2 the values are -9.67±0.12 and 14.73±0.40, respectively. These results are significantly more precise than those reported earlier by Garner et al. For the Mu reaction with H2 our results are in excellent agreement with the 3D quantum mechanical calculations of Schatz on the Liu–Siegbahn–Truhlar–Horowitz potential surface, but the data for both reactions compare less favorably with variational transition-state theory, particularly at the lower temperatures.NSERC (Canada) and the Petroleum Research Foundation of the Americal Chemical Society

The feasibility of achieving fair and effective access to law in the Australian welfare state : the lessons of revisiting the post-war experience of legal aid

In the 1970s Australia, like a number of comparable countries, reorganised the provision of legal aid. Within a few years, however, new 'problems' had emerged in 'access to justice'. In 1993, the Federal Government responded by charging a committee to identify 'solutions', some of whi£h were adopted in mid-199 5. Yet, the 'problems' of 'access to justice', and access to law, remain. This thesis considers whether these problems are capable of resolution. It begins by posing a general question: is fair and effective access to hiw a feasible expectation of citizens or governments in the Australian welfare state? In addressing this question, the thesis takes a 1990 official report into the problems facing legal aid in Australia as its starting point. This report left a legacy of unanswered questions. In retrospect, moreover, its questions highlighted the ongoing social significance of the problems in access to law for governments, business and citizens in post-war Australian society. The opening contention is that revisiting the origins and significance of the post-war experience of legal aid holds the key to determining the feasibility of achieving fair and effective access to law. The thesis nominates two major justifications in support of this contention. First, it asserts that revisiting the post-war experience will improve our understanding of 'why' Australia acted to enhance access to legal aid in the 1970s. Secondly, the thesis asserts that improving our understanding of the legal aid response will improve our capacity to understand the 'access to justice' response, and thereby the feasibility of any future reforms towards fair and effective access to law. Part I begins by explaining the history behind the national legal aid scheme, the reasons why it emerged in 1973-76 and its ideological context in modem Australian society. In doing so, it answers some of the unanswered questions of the 1990 report. However, Part II also demonstrates the limitations of institutional and ideological history in explaining the post-war experience, concluding that 'missing' parts of the story remain to be told. Thus, Part II begins by revisiting - in a crossnational context - the existing ideas which explain the post-war experience. It develops an alternative theory of the origins and significance of modem legal aid, which it proceeds to apply in revisiting - in the context of the Western world - the origins and significance of its post-war development. Part III proceeds to demonstrate 'why' and 'how' the lessons of revisiting the postwar experience enable us to better assess the feasibility of achieving fair and effective access to law. It begins by applying the insights, 'benchmarks' and analytical methodology of Part II to reconsider the origins of the new 'problems' in 'access to justice', the jettisoning of the legal aid response and the significance of the 1993 'access to justice' response. Part III concludes by briefly considering the implications of the thesis for the feasibility of achieving fair and effective access to law in the contemporary Australian welfare state

Atlantic corals

42 p. : ill., map ; 24 cm.Includes bibliographical references (p. 40-42)

Reaction kinetics of muonium with the halogen gases (F2, Cl2, and Br2)

Copyright @ 1989 American Institute of PhysicsBimolecular rate constants for the thermal chemical reactions of muonium (Mu) with the halogen gases—Mu+X2→MuX+X—are reported over the temperature ranges from 500 down to 100, 160, and 200 K for X2=F2,Cl2, and Br2, respectively. The Arrhenius plots for both the chlorine and fluorine reactions show positive activation energies Ea over the whole temperature ranges studied, but which decrease to near zero at low temperature, indicative of the dominant role played by quantum tunneling of the ultralight muonium atom. In the case of Mu+F2, the bimolecular rate constant k(T) is essentially independent of temperature below 150 K, likely the first observation of Wigner threshold tunneling in gas phase (H atom) kinetics. A similar trend is seen in the Mu+Cl2 reaction. The Br2 data exhibit an apparent negative activation energy [Ea=(−0.095±0.020) kcal mol−1], constant over the temperature range of ∼200–400 K, but which decreases at higher temperatures, indicative of a highly attractive potential energy surface. This result is consistent with the energy dependence in the reactive cross section found some years ago in the atomic beam data of Hepburn et al. [J. Chem. Phys. 69, 4311 (1978)]. In comparing the present Mu data with the corresponding H atom kinetic data, it is found that Mu invariably reacts considerably faster than H at all temperatures, but particularly so at low temperatures in the cases of F2 and Cl2. The current transition state calculations of Steckler, Garrett, and Truhlar [Hyperfine Interact. 32, 779 (986)] for Mu+X2 account reasonably well for the rate constants for F2 and Cl2 near room temperature, but their calculated value for Mu+Br2 is much too high. Moreover, these calculations seemingly fail to account for the trend in the Mu+F2 and Mu+Cl2 data toward pronounced quantum tunneling at low temperatures. It is noted that the Mu kinetics provide a crucial test of the accuracy of transition state treatments of tunneling on these early barrier HX2 potential energy surfaces.NSERC (Canada), Donors of the Petroleum Research Fund, administered by the American Chemical Society, for their partial support of this research and the Canada Council

Stony corals from the vicinity of Bimini, Bahamas, British West Indies. Bulletin of the AMNH ; v. 115, article 4

p. 219-262 [16] p. of plates : ill., maps ; 27 cm.Includes bibliographical references (p. 260-262)

Specificity in transmembrane helix-helix interactions defines a hierarchy of stability for sequence variants,

The folding, stability, and oligomerization of helical membrane proteins depend in part on a precise set of packing interactions between transmembrane helices. To understand the energetic principles of these helix-helix interactions, we have used alaninescanning mutagenesis and sedimentation equilibrium analytical ultracentrifugation to quantitatively examine the sequence dependence of the glycophorin A transmembrane helix dimerization. In all cases, we found that mutations to alanine at interface positions cost free energy of association. In contrast, mutations to alanine away from the dimer interface showed free energies of association that are insignificantly different from wild-type or are slightly stabilizing. Our study further revealed that the energy of association is not evenly distributed across the interface, but that there are several ''hot spots'' for interaction including both glycines participating in a GxxxG motif. Inspection of the NMR structure indicates that simple principles of protein-protein interactions can explain the changes in energy that are observed. A comparison of the dimer stability between different hydrophobic environments suggested that the hierarchy of stability for sequence variants is conserved. Together, these findings imply that the protein-protein interaction portion of the overall association energy may be separable from the contributions arising from protein-lipid and lipid-lipid energy terms. This idea is a conceptual simplification of the membrane protein folding problem and has implications for prediction and design. G enome sequencing efforts reveal that approximately 20% of ORFs in complex organisms may encode proteins containing at least one helical transmembrane segment (1). Despite these numbers, as well as the fact that membrane proteins carry out many essential cell functions, our understanding of the sequence-structure-function relationships for this class of proteins lags far behind that of soluble proteins. These realities underscore the importance of biophysical and structural work aimed toward understanding chemical principles of helical membrane protein structural stability. Because the phospholipid bilayer places structural constraints on a helical membrane protein, the folding of a polypeptide sequence into a helical membrane protein can be considered, experimentally and theoretically, in separable thermodynamic steps (2, 3). The usefulness of this framework arises from the fact that individual energetic processes can be independently studied. The principal features of a polypeptide sequence that will give rise to the formation of an independently stable transmembrane ␣-helix are generally known (3). This information has been used extensively in computational search algorithms with reasonable accuracy rates to identify potential helical transmembrane proteins (reviewed in ref. 3). Once this is accomplished, however, the helical membrane protein folding problem then becomes focused on understanding and predicting the side-to-side associations in which these preformed transmembrane ␣-helices will participate. It is this final thermodynamic step in helical membrane protein folding that we investigate in this study. In a continuing effort to understand the structural and energetic principles of the side-to-side interactions of transmembrane ␣-helices, we have quantitatively examined the sequence dependence of the glycophorin A transmembrane helix dimerization. The propensity of the glycophorin A transmembrane domain to dimerize in a sequence-specific manner has been a paradigm for study of transmembrane helix-helix association in hydrophobic environments (4-9). An additional advantage for detailed thermodynamic analysis of the GpA transmembrane segment (TMS) dimerization is the fact that a solution NMR structure has been solved (10). Together with considerations of principles of stability of helices in membranes, the NMR structure provides a three-dimensional model for interpretation of potential structural consequences due to mutation. Understanding the chemical principles driving the selfassociation of the glycophorin transmembrane ␣-helix is of particular interest because both the NMR structure and the exquisite sequence dependence determined by SDS͞PAGE suggest that a detailed geometry of van der Waals interactions specify and stabilize the dimer (4, 8, 10). Only one residue with a polar side-chain, Thr 87 , is found at the dimer interface. The solution NMR structure of the glycophorin A transmembrane dimer in dodecylphosphocholine micelles reveals no interhelical hydrogen bond at this position (10), although the recent solid state NMR data from Smith and coworkers (11) hints that Thr 87 might participate in an intermonomer hydrogen bond in lipid bilayers. Nevertheless, the energetic stabilization from such a hydrogen bond is uncertain. Recent studies on the introduction of polar side chains into model transmembrane peptides find that residues containing two polar side-chain atoms (such as asparagine) have a much greater tendency to drive transmembrane helix association than residues containing only one polar sidechain atom (threonine or serine; refs. 12 and 13). It has been proposed that side-chain rotamer entropy is not expected to play a large role in the self-association of the glycophorin A transmembrane ␣-helix (10). The interacting surface of the glycophorin A TMS contains only three residues with some rotamer freedom in an ␣-helix (Leu Abbreviations: TMS, transmembrane segment; C8E5, pentaoxylethylene-octylether. † To whom reprint requests should be addressed

Crystal Structures of Human Carboxylesterase 1 in Covalent Complexes with the Chemical Warfare Agents Soman and Tabun † , ‡

The organophosphorus nerve agents sarin, soman, tabun, and VX exert their toxic effects by inhibiting the action of human acetylcholinesterase, a member of the serine hydrolase superfamily of enzymes. The current treatments for nerve agent exposure must be administered quickly to be effective and they often do not eliminate long-term toxic side effects associated with organophosphate poisoning. Thus, there is significant need for effective prophylactic methods to protect at-risk personnel from nerve agent exposure, and protein-based approaches have emerged as promising candidates. We present the 2.7 Å resolution crystal structures of the serine hydrolase human carboxylesterase 1 (hCE1), a broad-spectrum drug metabolism enzyme, in covalent acyl-enzyme intermediate complexes with the chemical weapons soman and tabun. The structures reveal that hCE1 binds stereoselectively to these nerve agents; for example, hCE1 appears to react preferentially with the 104-fold more lethal PS stereoisomer of soman relative to the PR form. In addition, structural features of the hCE1 active site indicate that the enzyme may be resistant to dead-end organophosphate aging reactions that permanently inactivate other serine hydrolases. Taken together, these data provide important structural details toward the goal of engineering hCE1 into an organophosphate hydrolase and protein-based therapeutic for nerve agent exposure