Hans-Heinrich Limbach

Isotope Effects In Chemistry and Biology

Editorial Biography Theoretical Basis of Isotope Effects from an Autobiographical Perspective J. Bigeleisen Enrichment of Isotopes T. Ishida and Y. Fujii Comments on Selected Topics in Isotope Theoretical Chemistry M. Wolfsberg Condensed Matter Isotope Effects W.A. Van Hook Anharmonicities, Isotopes, and IR and NMR Properties of Hydrogen-Bonded Complexes J.E. Del Bene Isotope Effects on Hydrogen-Bond Symmetrization in Ice and Strong Acids at High Pressure K. Aoki Hydrogen Bond Isotope Effects Studied by NMR H-H. Limbach, G.S. Denisov and N.S. Golubev Isotope Effects and Symmetry of Hydrogen Bonds in Solution: Single- and Double-Well Potential J.S. Lau and C.L. Perrin NMR Studies of Isotope Effects of Compounds with Intramolecular Hydrogen Bonds P.E. Hansen Vibrational Isotope Effects in Hydrogen Bonds Z. Mielke and L. Sobczyk Isotope Selective Infrared Spectroscopy and Intramolecular Dynamics M. Hippler and M. Quack Nonmass-Dependent Isotope Effects R.E. Weston, Jr. Isotope Effects in the Atmosphere E. Roth, R. Letolle, C. M. Stevens, and F. Robert Isotope Effects for Exotic Nuclei O. Matsson Muonium - An Ultra-Light Isotope of Hydrogen E. Roduner The Kinetic Isotope Effect in the Photo-Dissociation Reaction of Excited-State Acids in Aqueous Solutions E. Pines The Role of an Internal-Return Mechanism on Measured Isotope Effects H.F. Koch Vibrationally Enhanced Tunneling and Kinetic Isotope Effects in Enzymatic Reactions S.D. Schwartz Kinetic Isotope Effects for Proton-Coupled Electron Transfer Reactions S. Hammes-Schiffer Kinetic Isotope Effects in Multiple Proton Transfer Z. Smedarchina, W. Siebrand, and A. Fernandez-Ramos Interpretation of Primary Kinetic Isotope Effects for Adiabatic and Nonadiabatic Proton-Transfer Reactions in a Polar Environment P.M. Kiefer and J.T. Hynes Variational Transition-State Theory and Multidimensional Tunneling for Simple and Complex Reactions in the Gas Phase, Solids, Liquids, and Enzymes D.G. Truhlar Computer Simulations of Isotope Effects in Enzyme Catalysis A. Warshel, Mats H. M. Olsson, and J. Villa-Freixa Chapter 24 Oxygen-18 Isotope Effects as a Probe of Enzymatic Activation of Molecular Oxygen Justine P. Roth and Judith P. Klinman Chapter 25 Solution and Computational Studies of Kinetic Isotope Effects in Flavoprotein and Quinoprotein Catalyzed Substrate Oxidations as Probes of Enzymic Hydrogen Tunneling and Mechanism J. Basran, L. Masgrau, M.J. Sutcliffe, and N.S. Scrutton Proton Transfer and Proton Conductivity in Condensed Matter Environment A.M. Kuznetsov and J. Ulstrup Mechanisms of CH-Bond Cleavage Catalyzed by Enzymes W. Siebrand and Z. Smedarchina Kinetic Isotope Effects as Probes for Hydrogen Tunneling in Enzyme Catalysis A. Kohen Hydrogen Bonds, Transition-State Stabilization, and Enzyme Catalysis R.L. Schowen Substrate and pH Dependence of Isotope Effects in Enzyme Catalyzed Reactions W.E. Karsten and P.F. Cook Catalysis by Alcohol Dehydrogenases B.V. Plapp Effects of High Hydrostatic Pressure on Isotope Effects D.B. Northrop Solvent Hydrogen Isotope Effects in Catalysis by Carbonic Anhydrase: Proton Transfer through Intervening Water Molecules D.N. Silverman and I. Elder Isotope Effects from Partitioning of Intermediates in Enzyme-Catalyzed Hydroxylation Reactions Paul F. Fitzpatrick Chlorine Kinetic Isotope Effects on Biological Systems P. Paneth Nucleophile Isotope Effects V.E. Anderson, A.G. Cassano, and M.E. Harris Enzyme Mechanisms from Isotope Effects W. W. Cleland Catalysis and Regulation in the Soluble Methane Monooxygenase System: Applications of Isotopes and Isotope Effects J.D. Lipscomb Secondary Isotope Effects A.C. Hengge Isotope Effects in the Characterization of Low Barrier Hydrogen Bonds P.A. Frey Theory and Practice of Solvent Isotope Effects D.M. Quinn Enzymatic Binding Isotope Effects and the Interaction of Glucose with Hexokinase B.E. Lewis and V.L. Schramm Index

Ruthenium Nanoparticles inside Porous [Zn4O(bdc)3] by Hydrogenolysis of Adsorbed [Ru(cod)(cot)]: A Solid-State Reference System for Surfactant-Stabilized Ruthenium Colloids

The gas-phase loading of [Zn4O(bdc)3] (MOF-5; bdc = 1,4-benzenedicarboxylate) with the volatile compound [Ru(cod)(cot)] (cod = 1,5-cyclooctadiene, cot = 1,3,5-cyclooctatriene) was followed by solid-state (13)C magic angle spinning (MAS) NMR spectroscopy. Subsequent hydrogenolysis of the adsorbed complex inside the porous structure of MOF-5 at 3 bar and 150 degrees C was performed, yielding ruthenium nanoparticles in a typical size range of 1.5-1.7 nm, embedded in the intact MOF-5 matrix, as confirmed by transmission electron microscopy (TEM), selected area electron diffraction (SAED), powder X-ray diffraction (PXRD), and X-ray absorption spectroscopy (XAS). The adsorption of CO molecules on the obtained Ru@MOF-5 nanocomposite was followed by IR spectroscopy. Solid-state (2)H NMR measurements indicated that MOF-5 was a stabilizing support with only weak interactions with the embedded particles, as deduced from the surprisingly high mobility of the surface Ru-D species in comparison to surfactant-stabilized colloidal Ru nanoparticles of similar sizes. Surprisingly, hydrogenolysis of the [Ru(cod)(cot)]3.5@MOF-5 inclusion compound at the milder condition of 25 degrees C does not lead to the quantitative formation of Ru nanoparticles. Instead, formation of a ruthenium-cyclooctadiene complex with the arene moiety of the bdc linkers of the framework takes place, as revealed by (13)C MAS NMR, PXRD, and TEM.

Pyridine-15N: A mobile NMR sensor for surface acidity and surface defects of mesoporous silica

The hydrogen bond interaction of pyridine with the silanol groups of the inner surfaces of MCM-41 and SBA-15 ordered mesoporous silica has been studied by a combination of solid-state NMR techniques. The pore diameters were varied between 3 and 4 nm for MCM-41 and between 7 and 9 nm for SBA-15. 1 H MAS experiments performed under magic angle spinning (MAS) conditions in the absence and the presence of pyridine-d 5 reveal that the large majority of silanol groups are located in the inner surfaces, isolated from each other but able to form hydrogen bonds with pyridine. On the other hand, low- and room-temperature 1 5 N CPMAS and MAS experiments (CP ≡ cross-polarization) performed on pyridine- 1 5 N show that at low concentrations all pyridine molecules are involved in hydrogen bonds with the surface silanol groups. In the presence of an excess of pyridine, a non-hydrogen-bonded pyridine phase is observed at 120 K in the slow hydrogen bond exchange regime and associates with an inner core phase. From these measurements, the number of pyridine molecules bound to the inner surfaces corresponding to the number of silanol groups could be determined to be n O H 3 nm - 2 for MCM-41 and 3.7 nm - 2 for SBA-15. At room temperature and low concentrations, the pyridine molecules jump rapidly between the hydrogen-bonded sites. In the presence of an excess of pyridine, the hydrogen-bonded binding sites are depleted as compared to low temperatures, leading to smaller apparent numbers n O H . Using a correlation established previously between the 1 5 N and 1 H chemical shifts and the NHO hydrogen bond geometries, as well as with the acidity of the proton donors, the distances in the pyridine-hydroxyl pairs were found to be about r H N = 1.68 A, r O H = 1.01 A, and r O N = 2.69 A. This geometry corresponds in the organic solid state to acids exhibiting in water a pK a of about 4. Roomtemperature 1 5 N experiments on static samples of pyridine- 1 5 N in MCM-41 at low coverage show a residual 1 5 N chemical shift anisotropy, indicating that the jumps of pyridine between different different silanol hydrogen bond sites is accompanied by an anisotropic reorientational diffusion. A quantitative analysis reveals that in this regime the rotation of pyridine around the molecular C 2 axis is suppressed even at room temperature, and that the angle between the Si-O axes and the OH axes of the isolated silanol groups is about 47°. These results are corroborated by 2 H NMR experiments performed on pyridine-4-d 1 . In contrast, in the case of SBA-15 with the larger pore diameters, the hydrogen bond jumps of pyridine are associated with an isotropic rotational diffusion, indicating a high degree of roughness of the inner surfaces. This finding is correlated with the finding by 2 9 Si CPMAS of a substantial amount of Si(OH) 2 groups in SBA-15. in contrast to the MCM-41 materials. The Si(OH) 2 groups are associated with surface defects, exhibiting not only silanol groups pointing into the pore center but also silanol groups pointing into other directions of space including the pore axes, leading to the isotropic surface diffusion. All results are used to develop molecular models for the inner surface structure of mesoporous silica which may be a basis for future simulations of the surfaces of mesoporous silica.

NUCLEAR SCALAR SPIN - SPIN COUPLING REVEALS NOVEL PROPERTIES OF LOW-BARRIER HYDROGEN BONDS IN A POLAR ENVIRONMENT

The structure of the hydrogen bridge 19 F· ·· 1 H· ·· 15 N in the acid - base complex A ··· H ··· B formed by HF and ( 15 N)2,4,6-trimethylpyridine in CDF3/ CDF2Cl has been studied between 112 K and 200 K by low-temperature, multinuclear NMR spectroscopy. For the first time scalar spin - spin coupling between all three nuclei of a hydrogen bridge is observed. This bridge exhibits a two-bond coupling constant 2 J19F15N of about 96 Hz, which is larger than the one-bond coupling constants 1 J1H15N and 1 J19F1H. The latter are strongly dependent on temperature. The function 1 J1H15Na f( 1 J19F1H) cannot be described in terms of a conventional equilibrium between the molecular and the zwitterionic form, but only with the intermediate forma- tion of very strongly hydrogen-bonded complexes of the type A dˇ ··· H· ·· B da that exhibit a vanishing or very small barrier for the proton motion. Here, the difference between the covalent bond and the hydrogen bond disappears even in the case of a polar solvents, as indicated by the large value of 2 J19F15N. Implications for the mechanism of pro- ton transfer and of acid - base catalyzed enzyme reactions in a locally aprotic but polar environment are discussed.

Hydrogen bonds and proton transfer in general-catalytic transition-state stabilization in enzyme catalysis.

The question of the nature of the proton bridge involved in general acid-base catalysis in both enzymic and non-enzymic systems is considered in the light of long-known but insufficiently appreciated work of Jencks and his coworkers and of more recent results from neutron-diffraction crystallography and NMR spectroscopic studies, as well as results from isotope-effect investigations. These lines of inquiry lead toward the view that the bridging proton, when between electronegative atoms, is in a stable potential at the transition state, not participating strongly in the reaction-coordinate motion. Furthermore they suggest that bond order is well-conserved at unity for bridging protons, and give rough estimates of the degree to which the proton will respond to structural changes in its bonding partners. Thus if a center involved in general-catalytic bridging becomes more basic, the proton is expected to move toward it while maintaining a unit total bond order. For a unit increase in the pK of a bridging partner, the other partner is expected to acquire about 0.06 units of negative charge. The implications are considered for charge distribution in enzymic transition states as the basicity of catalytic residues changes in the course of molecular evolution or during progress along a catalytic pathway.

Arrhenius curves of hydrogen transfers: tunnel effects, isotope effects and effects of pre-equilibria

In this paper, the Arrhenius curves of selected hydrogen-transfer reactions for which kinetic data are available in a large temperature range are reviewed. The curves are discussed in terms of the one-dimensional Bell–Limbach tunnelling model. The main parameters of this model are the barrier heights of the isotopic reactions, barrier width of the H-reaction, tunnelling masses, pre-exponential factor and minimum energy for tunnelling to occur. The model allows one to compare different reactions in a simple way and prepare the kinetic data for more-dimensional treatments. The first type of reactions is concerned with reactions where the geometries of the reacting molecules are well established and the kinetic data of the isotopic reactions are available in a large temperature range. Here, it is possible to study the relation between kinetic isotope effects (KIEs) and chemical structure. Examples are the tautomerism of porphyrin, the porphyrin anion and related compounds exhibiting intramolecular hydrogen bonds of medium strength. We observe pre-exponential factors of the order of kT/h≅1013 s−1 corresponding to vanishing activation entropies in terms of transition state theory. This result is important for the second type of reactions discussed in this paper, referring mostly to liquid solutions. Here, the reacting molecular configurations may be involved in equilibria with non- or less-reactive forms. Several cases are discussed, where the less-reactive forms dominate at low or at high temperature, leading to unusual Arrhenius curves. These cases include examples from small molecule solution chemistry like the base-catalysed intramolecular H-transfer in diaryltriazene, 2-(2′-hydroxyphenyl)-benzoxazole, 2-hydroxy-phenoxyl radicals, as well as in the case of an enzymatic system, thermophilic alcohol dehydrogenase. In the latter case, temperature-dependent KIEs are interpreted in terms of a transition between two regimes with different temperature-independent KIEs.

H/D isotope effects on the low-temperature NMR parameters and hydrogen bond geometries of (FH)2F− and (FH)3F− dissolved in CDF3/CDF2Cl

Using liquid state 1H, 2H and 19F NMR spectroscopy in the temperature range 110–130 K we have studied the hydrogen-bonded anions (FH)2F− and (FH)3F− and their partially and fully deuterated analogs dissolved in the low-freezing freon mixture CDF3/CDF2Cl, in the presence of (C4H9)4N+ as the counter cation. The spin multiplets of the three isotopologs HH, HD, DD of (FH)2F−, and of the four isotopologs HHH, HHD, HDD, DDD of (FH)3F− have been resolved and assigned. Thus, we were able to determine the zero-, one- and two-bond H/D isotope effects on the hydrogen and fluorine NMR chemical shifts as well as isotope effects on the scalar spin–spin hydrogen–fluorine and fluorine–fluorine coupling constants. Using the valence bond order model these NMR data are related to H/D isotope effects on the hydrogen bond geometries. A semi-quantitative interpretation of the observed long range isotope effects is proposed in terms of an anti-cooperative coupling between the hydrogen bonds within each anion. The experimental data can be rationalized in terms of an empirical NMR isotope sum rule, which is analogous to a similar rule for the vibrational frequencies.

IR‐spectroscopic study of isotope effects on the NH/ND‐stretching bands of meso‐tetraphenylporphine and vibrational hydrogen tunneling

The IR spectra of meso‐tetraphenylporphine (TPP) dissolved in CCl4 have been measured in the NH and ND stretching band region as a function of isotopic substitution using a newly constructed vacuum IR cell. Thus, it was possible for the first time to localize the NH and ND stretching bands of TPP–HD, which are characterized by the wave numbers 3335 and 2493 cm−1. TPP–H2 and TPP–D2 were found to absorb at lower frequencies, namely 3318 and 2482 cm−1. The observation of this band shift allows one to identify the observed NH and ND stretching bands in TPP–H2 and TPP–D2. They arise from antisymmetric stretching vibrations, the symmetric bands being forbidden in the IR spectra. NH/ND stretching bandwidths of the order of 20 cm−1 were observed, which is unusually small for proton transfer systems. This observation further confirms our previous conclusions from the primary HH/HD/DD kinetic isotope effects on the tautomerism in this molecule, namely that the motion of the hydrogen atoms takes place in a coupled m...

The hydrogen-bonded 2-pyridone dimer model system. 1. Combined NMR and FT-IR spectroscopy study.

2-Pyridone (PD), converting to 2-hydroxypyridine (HP) through a lactam-lactim isomerization mechanism, can form three different cyclic dimers by hydrogen bond formation: (PD)(2), (PD-HP), and (HP)(2). We investigate the complexation chemistry of pyridone in dichloromethane-d(2) using a combined NMR and Fourier transform infrared (FT-IR) approach. Temperature-dependent (1)H NMR spectra indicate that at low temperatures (<200 K) pyridone in solution predominantly exists as a cyclic (PD)(2) dimer, in exchange with PD monomers. At higher temperatures a proton exchange mechanism sets in, leading to a collapse of the doublet of (15)N labeled 2-pyridone. Linear FT-IR spectra indicate the existence of several pyridone species, where, however, a straightforward interpretation is hampered by extensive spectral overlap of many vibrational transitions in both the fingerprint and the NH/OH stretching regions. Two-dimensional IR correlation spectroscopy applied on concentration-dependent and temperature-dependent data sets reveals the existence of the (PD)(2) cyclic dimer, of PD-CD(2)Cl(2) solute-solvent complexes, and of PD-PD chainlike dimers. Regarding the difference in effective time scales of the NMR and FT-IR experiments, milliseconds vs (sub)picoseconds, the cyclic dimers (PD-HP) and (HP)(2), and the chainlike conformations HP-PD, may function as intermediates in reaction pathways through which the protons exchange between PD units in cyclic (PD)(2).

CPMAS Polarization Transfer Methods for Superposed Chemical Exchange and Spin Diffusion in Organic Solids

Abstract The question of how CPMAS polarization-transfer experiments (CP, cross polarization; MAS, magic-angle spinning) should be conducted in order to distinguish between slow chemical exchange and spin diffusion in the solid state has been studied. Both contributions can be separated by performing different types of polarization-transfer experiments in the laboratory and the rotating frame, since dynamics of spin diffusion but not chemical exchange differs from one experiment to the next. Generally, if both processes are present, polarization transfer is expected to be nonexponential and chemical-exchange as well as spin-diffusion rate constants can be obtained in one series of experiments. If the exchange is symmetric, however, polarization transfer is single exponential and a combination of different pulse experiments is required for obtaining rate constants of both processes. The results for 15N CPMAS NMR polarization-transfer experiments on crystalline meso-tetratolylporphin-15N4 (TTP) are presented. Experiments in the laboratory frame show that spin diffusion between the 15N atoms of TTP is characterized by a temperature-independent rate constant. The nature of this process was established by 1H decoupling during the mixing time, which results in quenching of the polarization transfer. Thus, the role of the 1H spin reservoir for laboratory-frame spin diffusion among chemically inequivalent 15N spins in 15N-enriched material is confirmed. At higher temperatures, polarization transfer in the laboratory and the rotating frame is observed due to a symmetric exchange of the nitrogen atoms arising from a double proton transfer which has been previously established. The double proton transfer rates observed with the different polarization-transfer methods agree well with the values predicted from high-temperature lineshape analysis and are found to be very close to the solution data.