Christopher A Hunter

The University of Sheffield, Sheffield, England, United Kingdom

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Publications (209)1259.22 Total impact

  • Martin Volk, Lilia Milanesi, J Waltho, Christopher A Hunter, G S Beddard
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    ABSTRACT: Although protein folding is often described by motion on a funnel-shaped overall topology of the energy landscape, the many local interactions that can occur result in considerable landscape roughness which slows folding by increasing internal friction. Recent experimental results have brought to light that this roughness also causes unusual diffusional behaviour of the backbone of an unfolded protein, i.e. the relative motion of protein sections cannot be described by the normal diffusion equation, but shows strongly subdiffusional behaviour with a nonlinear time dependence of the mean square displacement, <r2(t)> ∝ tα (α << 1). This results in significantly slower configurational equilibration than had been assumed hitherto. Analysis of the results also allows quantification of the energy landscape roughness, i.e. the root-mean-squared depth of local minima, yielding a value of 4-5 kBT for a typical small protein.
    Physical Chemistry Chemical Physics 11/2014; · 4.20 Impact Factor
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    ABSTRACT: A new strategy for determining thermodynamic effective molarities (EM) for macrocylisation reactions using dynamic combinatorial chemistry under dilute conditions is presented. At low concentrations, below the critical value, Dynamic Libraries (DLs) of bifunctional building blocks contain only cyclic species, so it is not possible to quantify the equilibria between linear and cyclic species. However, addition of a monofunctional chain stopper can be used to promote the formation of linear oligomers allowing measurement of EM for all cyclic species present in the DL. The effectiveness of this approach was demonstrated for DLs generated from mixtures of 1,3-diimine calix[4]arenes, linear diaminoalkanes and monoaminoalkanes. For macrocycles deriving from one bifunctional calixarene and one diamine, there is an alternating pattern of EM values with the number of methylene units in the diamine: odd numbers give significantly higher EMs than even numbers. For odd numbers of methylene units, the alkyl chain can adopt an extended all anti conformation, whereas for even numbers of methylene units, gauche conformations are required for cyclisation, and the associated strain reduces EM. The value of EM for the five-carbon linker indicates that this macrocycle is a strainless ring.
    Chemical Science 09/2014; · 8.31 Impact Factor
  • William Cullen, Simon Turega, Christopher A. Hunter, Michael D. Ward
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    ABSTRACT: A range of organic molecules with acidic or basic groups exhibit strong pH-dependent binding inside the cavity of a polyhedral coordination cage. Guest binding in aqueous solution is dominated by a hydrophobic contribution which is compensated by stronger solvation when the guests become cationic (by protonation) or anionic (by deprotonation). The Parkinson's drug 1-amino-adamantane (‘amantadine’) binds with an association constant of 104 M−1 in the neutral form (pH greater than 11), but the stability of the complex is reduced by three orders of magnitude when the guest is protonated at lower pH. Monitoring the uptake of the guests into the cage cavity was facilitated by the large upfield shift for the 1H NMR signals of bound guests due to the paramagnetism of the host. Although the association constants are generally lower, guests of biological significance such as aspirin and nicotine show similar behaviour, with a substantial difference between neutral (strongly binding) and charged (weakly binding) forms, irrespective of the sign of the charged species. pH-dependent binding was observed for a range of guests with different functional groups (primary and tertiary amines, pyridine, imidazole and carboxylic acids), so that the pH-swing can be tuned anywhere in the range of 3.5–11. The structure of the adamantane-1-carboxylic acid complex was determined by X-ray crystallography: the oxygen atoms of the guest form CHO hydrogen bonds with one of two equivalent pockets on the internal surface of the host. Reversible uptake and release of guests as a function of pH offers interesting possibilities in any application where controlled release of a molecule following an external stimulus is required.
    Chemical Science 08/2014; · 8.31 Impact Factor
  • Craig C Robertson, Robin N Perutz, Lee Brammer, Christopher A Hunter
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    ABSTRACT: The effect of solvent on the stabilities of complexes involving a single H-bond or halogen-bond (X-bond) has been quantified. Association constants for binary complexes of 4-(phenylazo)phenol, molecular iodine, tetramethylurea and tetramethylthiourea have been measured in fifteen different solvents by UV/vis absorption and 1H NMR titration experiments. The stabilities of the H-bonded complexes decrease by more than three orders of magnitude with increasing solvent polarity. In contrast, the X-bonded complex of molecular iodine with tetramethylthiourea is remarkably insensitive to the nature of the solvent (association constants measured in alkanes and alcohols are similar). The results suggest that, in contrast to H-bonds, where electrostatics determine thermodynamic stability, charge-transfer interactions make a major contribution to the stability of these X-bonded complexes rendering them resistant to increases in solvent polarity.
    Chemical Science 07/2014; · 8.31 Impact Factor
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    ABSTRACT: Size and shape criteria for guest binding inside the cavity of an octanuclear cubic coordination cage in water have been established using a new fluorescence displacement assay to quantify guest binding. For aliphatic cyclic ketones of increasing size (from C5 to C11), there is a linear relationship between ∆G for guest binding and the guest's surface area: the change in ∆G for binding is 0.3 kJ mol-1 Å-2, corresponding to 5 kJ mol-1 for each additional CH2 group in the guest, in good agreement with expectations based on hydrophobic desolvation. The highest association constant was K = 1.2 x 106 M-1 for cycloundecanone, whose volume is approximately 50% of that cavity volume; for larger C12 and C13 cyclic ketones, the association constant progressively decreases as the guests become too large. For a series of C10 aliphatic ketones, differing in shape but not size, ∆G for guest binding showed no correlation with surface area. These guests are close to the volume limit of the cavity (cf. Rebek's 55% rule), so the association constant is sensitive to shape complementarity, with small changes in guest structure resulting in large changes in binding affinity. The most flexible members of this series (linear aliphatic ketones) did not bind, whereas the more preorganised cyclic ketones all have association constants of 104 -105 M-1. A crystal structure of the cage•cycloundecanone complex shows that the guest carbonyl oxygen is directed into a binding pocket defined by a convergent set of CH groups, which act as weak H-bond donors, and also shows close contacts between the exterior surface of the disc-shaped guest and the interior surface of the pseudo-spherical cage cavity despite the slight mismatch in shape.
    Journal of the American Chemical Society 05/2014; · 10.68 Impact Factor
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    ABSTRACT: Formulation of solids as cocrystals offers an opportunity to modulate physical properties, so identification of cocrystal formers (CCFs) for an active pharmaceutical ingredient is an area of significant interest. Exhaustive experimental screening would be time-consuming, but we have developed a computational method for identifying CCFs that have a high chance of success based on calculated functional group interaction energies. This virtual screening tool has been applied to nalidixic acid cocrystals. Calculations on a library of 310 compounds identified the 44 most promising CCFs for formation of nalidixic acid cocrystals. Six of these compounds were already known to form cocrystals, and experimental work was undertaken on the remaining 38 compounds. X-ray powder diffraction (XRPD) of mixtures obtained from grinding experiments identified seven CCFs that form new solid phases with nalidixic acid. Infrared spectroscopy and differential scanning calorimetry confirm that these new solid phases are different from the pure components. Further structural characterization was not possible for the skatole, 2,4-dihydroxybenzoic acid, and 3,4-dihydroxybenzoic acid cocrystals, but X-ray crystal structures were obtained from single crystals of the 1:1 tert-butylhydroquinone cocrystal and of the 1:1 propyl gallate cocrystal and from the XRPD pattern for the 1:1 2-phenylphenol cocrystal and for the 1:2 indole cocrystal. The results suggest that success rates in cocrystal screening can be significantly improved by application of computational filters to select the most appropriate CCFs for experimental study
    Crystal Growth & Design 03/2014; · 4.69 Impact Factor
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    Dataset: To list 1
  • Michael A Jinks, Hongmei Sun, Christopher A Hunter
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    ABSTRACT: The association constants for formation of 1 : 1 complexes between five different imidazole ligands and eight different porphyrins have been measured by UV/vis titration experiments in two different solvents, toluene and 1,1,2,2-tetrachloroethane (TCE). Ligands equipped with H-bond acceptors (ester or amide) and porphyrins equipped with H-bond donors (phenol) can make H-bonds in addition to the zinc-nitrogen coordination interaction. The free energy contributions of these H-bonds to the overall stabilities of the complexes were determined using chemical double mutant cycles. Amide-phenol H-bonds contribute up to 5 kJ mol(-1) to the free energy change on complexation, and ester-phenol H-bonds contribute up to 3 kJ mol(-1). Porphyrin-ligand combinations with poor geometric complementarity do not make detectable H-bonding interactions. Effective molarities (EM) for the formation of H-bonds in the complexes were estimated by comparing the equilibrium constants for formation of the intramolecular interaction with the corresponding intermolecular interaction: the values are between 3 mM and 200 mM, which is comparable to previous results obtained for porphyrin-pyridine complexes. The values of EM measured for flexible and rigid ligand systems are comparable. This suggests that there is a trade off between restriction of conformational mobility in the flexible ligands and geometric strain in the rigid ligands, which results in similar binding affinities.
    Organic & Biomolecular Chemistry 01/2014; · 3.57 Impact Factor
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    ABSTRACT: A virtual cocrystal screening method based on calculated gas phase molecular electrostatic potential surfaces (MEPS) of the individual components has been validated using experimental cocrystal screens reported in the literature. The noncovalent interactions of a molecule with its environment are described by a discrete set of independent surface site interaction points (SSIPs), whose properties can be calculated from the ab initio MEPS. The stability of a crystal is estimated based on pairing SSIPs such that the sum of the pairwise interaction energies is optimized. This provides a means of calculating the relative stability of a cocrystal compared with the pure components without knowing anything about the three-dimensional structures of the crystalline states. For a set of potential crystal coformers (CCF), the difference between interaction site pairing energies of different solid forms (ΔE) provides a method for ranking CCFs based on the calculated probability of cocrystal formation. The method was applied to cocrystal screens of 18 compounds that reported both hits and misses, and in most cases, the virtual cocrystal screen reproduces experimental results well. In lists of CCFs ranked by ΔE, the experimentally observed hits were significantly enriched at the top, and this indicates that virtual screening is a promising tool for focusing experimental efforts on the most promising CCF candidates.
    Crystal Growth & Design 01/2014; 14(1):165-171. · 4.69 Impact Factor
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    ABSTRACT: The formation of halogen bonds from iodopentafluorobenzene and 1-iodoperfluorohexane to a series of bis(eta5-cyclopentadienyl)metal hydrides (Cp2MH3, M = Ta, 1, Cp2MH2 M = Mo, 2, W, 3, Cp2ReH, 4, Cp2Ta(H)CO, 5, Cp = eta5 cyclopentadienyl) is demonstrated by 1H NMR spectroscopy. Interaction enthalpies and entropies for complex 1 with C6F5I and C6F13I are reported (ΔH° -10.9 ± 0.4 and -11.8 ± 0.3 kJ mol-1; ΔS° -38 ± 2 and -34 ± 2 J mol-1 K-1, respectively) and found to be stronger than that for the hydrogen bond donor indole (ΔH° -7.3 ± 0.1 kJ mol-1, ΔS° -24 ± 1 J mol-1 K-1). For the more reactive complexes 2, 3, 4, and 5, measurements were limited to a determination of their low temperature (212 K) association constants with iodopentafluorobenzene and found to be 2.9 ± 0.2, 2.5 ± 0.1, <1.5 and 12.5 ± 0.3 M-1, respectively.
    Journal of the American Chemical Society 12/2013; · 10.68 Impact Factor
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    ABSTRACT: We have prepared a series of mononuclear fac and mer isomers of Ru(ii) complexes containing chelating pyrazolyl-pyridine ligands, to examine their differing ability to act as hydrogen-bond donors in MeCN. This was prompted by our earlier observation that octanuclear cube-like coordination cages that contain these types of metal vertex can bind guests such as isoquinoline-N-oxide (K = 2100 M(-1) in MeCN), with a significant contribution to binding being a hydrogen-bonding interaction between the electron-rich atom of the guest and a hydrogen-bond donor site on the internal surface of the cage formed by a convergent set of CH2 protons close to a 2+ metal centre. Starting with [Ru(L(H))3](2+) [L(H) = 3-(2-pyridyl)-1H-pyrazole] the geometric isomers were separated by virtue of the fact that the fac isomer forms a Cu(i) adduct which the mer isomer does not. Alkylation of the pyrazolyl NH group with methyl iodide or benzyl bromide afforded [Ru(L(Me))3](2+) and [Ru(L(bz))3](2+) respectively, each as their fac and mer isomers; all were structurally characterised. In the fac isomers the convergent group of pendant -CH2R or -CH3 protons defines a hydrogen-bond donor pocket; in the mer isomer these protons do not converge and any hydrogen-bonding involving these protons is expected to be weaker. For both [Ru(L(Me))3](2+) and [Ru(L(bz))3](2+), NMR titrations with isoquinoline-N-oxide in MeCN revealed weak 1 : 1 binding (K ≈ 1 M(-1)) between the guest and the fac isomer of the complex that was absent with the mer isomer, confirming a difference in the hydrogen-bond donor capabilities of these complexes associated with their differing geometries. The weak binding compared to the cage however occurs because of competition from the anions, which are free to form ion-pairs with the mononuclear complex cations in a way that does not happen in the cage complexes. We conclude that (i) the presence of fac tris-chelate sites in the cage to act as hydrogen-bond donors, and (ii) exclusion of counter-ions from the central cavity leaving these hydrogen-bonding sites free to interact with guests, are both important design criteria for future coordination cage hosts.
    Dalton Transactions 10/2013; · 4.10 Impact Factor
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    ABSTRACT: A liquid is composed of an ensemble of molecules that populate a large number of different states, so calculation of the solvation energy of a molecule in solution requires a method for summing the interactions with the environment over all of these states. The surface site interaction model for the properties of liquids at equilibrium (SSIMPLE) simplifies the surface of a molecule to a discrete number of specific interaction sites (SSIPs). The thermodynamic properties of these interaction sites can be characterised experimentally, for example, through measurement of association constants for the formation of simple complexes that feature a single H-bonding interaction. Correlation of experimentally determined solution phase H-bond parameters with gas phase ab initio calculations of maxima and minima on molecular electrostatic potential surfaces (MEPS) provides a method for converting gas phase calculations on isolated molecules to parameters that can be used to estimate solution phase interaction free energies. This approach has been generalised using a footprinting technique that converts an MEPS into a discrete set of SSIPs (each described by a polar interaction parameter, εi). These SSIPs represent the molecular recognition properties of the entire surface of the molecule. For example, water is described by four SSIPs, two H-bond donor sites and two H-bond acceptor sites. A liquid mixture is described as an ensemble of SSIPs that represent the components of the mixture at appropriate concentrations. Individual SSIPs are assumed to be independent, so speciation of SSIP contacts can be calculated based on properties of the individual SSIP interactions, which are given by the sum of a polar (εiεj) and a non-polar (EvdW) interaction term. Results are presented for calculation the free energies of transfer of a range of organic molecules from the pure liquid into water, from the pure liquid into n-hexadecane, from n-hexadecane into water, from n-octanol into water, and for the transfer of water from pure water into a range of organic liquids. The agreement with experiment is accurate to within 1.6-3.9 kJ mol(-1) root mean square difference, which suggests that the SSIMPLE approach is a promising method for estimation of solvation energies in more complex systems.
    Physical Chemistry Chemical Physics 09/2013; · 4.20 Impact Factor
  • Hongmei Sun, Christopher A Hunter, Cristina Navarro, Simon Turega
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    ABSTRACT: Effective molarity (EM) is a key parameter that determines the efficiency of a range of supramolecular phenomena from the folding of macromolecules to multivalent ligand binding. Coordination complexes formed between zinc porphyrins equipped H-bond donor sites and pyridine ligands equipped with H-bond acceptor sites have allowed systematic quantification of EM values for the formation of intramolecular H-bonds in 240 different systems. The results provide insights into the relationship of EM to supramolecular architecture, H-bond strength, and solvent. Previous studies on ligands equipped with phosphonate diester and ether H-bond acceptors were inconclusive, but the experiments described here on ligands equipped with phosphine oxide, amide, and ester H-bond acceptors resolve these ambiguities. Chemical double-mutant cycles were used to dissect the thermodynamic contributions of individual H-bond interactions to the overall stabilities of the complexes and hence determine the values of EM, which fall in the range 1-1000 mM. Solvent has little effect on EM, and the values measured in toluene and 1,1,2,2-tetrachloroethane are similar. For H-bond acceptors that have similar geometries but different H-bond strengths (amide and ester), the values of EM are very similar. For H-bond acceptors that have different geometries but similar H-bond strengths (amide and phosphonate diester), there is little correlation between the values of EM. These results imply that supramolecular EMs are independent of solvent and intrinsic H-bond strength but depend on supramolecular architecture and geometric complementarity.
    Journal of the American Chemical Society 08/2013; · 10.68 Impact Factor
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    ABSTRACT: The association constants for formation a 1:1 complex between 4-phenyl azophenol and tri-n-butylphosphine oxide were measured in mixtures of n-octane and n-decanol, n-octane and n-hexanoic acid, and n-octane and 2-ethylhexyl acetamide. The experiments provide insight into the competition between solvent self-association and solvent-solute interactions in these systems. The solvation properties of the three polar solvents are quite different from one another and from polar solvents that do not self-associate. Carboxylic acids form dimers in concentrated solution (>1 mM in alkanes). Carboxylic acid dimers have exposed H-bond acceptor sites that solvate H-bond donor solutes with a similar binding affinity to carboxylic acid monomers. The carboxylic acid H-bond donor site is inaccessible in the dimer and is not available to solvate H-bond acceptor solutes. The result is that solvation of H-bond acceptor solutes is in competition with solvent dimerization, whereas solvation of H-bond donor solutes is not. Secondary amides form linear polymers in concentrated solution (>10 mM in alkanes). The solvation properties of the secondary amide aggregates are similar to those of carboxylic acid dimers. Solvation of H-bond acceptor solutes must compete with solvent self-association, because the amide H-bond donor site is not accessible in the middle of a polymeric aggregate. However, the amide aggregates have exposed H-bond acceptor sites, which solvate H-bond donor solutes with similar binding affinity to amide monomers. Alcohols form cyclic tetramers at concentrations of 100 mM in alkanes, and these cyclic aggregates are in equilibrium with linear polymeric aggregates at concentrations above 1 M. The alcohol aggregates have exposed H-bond acceptor sites that solvate H-bond donor solutes with similar binding affinity to alcohol monomers. Although the alcohol H-bond donor sites are involved in H-bond interactions with other alcohols in the aggregates, these sites are sufficiently exposed to form a second bifurcated H-bond with H-bond acceptor solutes, and these interactions have a similar binding affinity to alcohol monomers. The result is that self-association of alcohols does not compete with solvation of solutes, and alcohols are significantly more polar solvents than expected based on the properties of alcohol monomers.
    Journal of the American Chemical Society 08/2013; · 10.68 Impact Factor
  • Christopher A. Hunter
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    ABSTRACT: The electrostatic solvent competition model developed to estimate solvent effects on solution phase association constants for formation of 1:1 complexes between two solutes has been extended to provide a general treatment of intermolecular interactions in the liquid state. The interactions of a molecule with its solvation shell are described by a set of surface site interaction points (SSIPs). An SSIP represents a molecular surface area of 9.5 Å2, a volume of 5 Å3, and is characterised by an electrostatic interaction parameter, εi, obtained from the molecular electrostatic potential surface calculated in the gas phase or from functional group H-bond parameters experimentally determined in solution. A liquid is treated as an ensemble of SSIPs that interact with a probability governed by the sum of the electrostatic interaction energy, given by εiεj, and a constant van der Waals term of −5.6 kJ mol−1. The speciation of SSIP contacts is determined as a Boltzmann-weighted population of states, and this allows calculation of a variety of thermodynamic properties of solutions. The model assumes that unbound states are possible for SSIPs due to the large amount of void space present in a liquid. This provides a straightforward thermodynamic connection between different phases, because unbound states have the same chemical potential in different environments. The free energy of transfer of a molecule between two different liquid phases is calculated as the sum of a binding energy, which is a measure of the total interaction of all SSIPs in the molecule with the liquid, and a confinement energy, which is a measure of the entropic cost of confining the molecular SSIPs to that phase. Calculated liquid–liquid transfer free energies agree with experiment (±1 to 3 kJ mol−1) for a collection of alkanes, ethers, alcohols and water. The calculations provide insight into the molecular basis of the hydrophobic effect, the origin of the difference in H-bond populations in water and alcohols, and the differences between 1-octanol and n-hexadecane partition coefficients as measures of hydrophobicity. Solvent effects on association constants for formation of 1:1 H-bonded complexes are also reproduced by the calculations (±0.5 log units). In addition to comparison with experimental thermodynamic data, this model can also be validated using spectroscopic data on the speciation of different H-bonded states in solution.
    Chemical Science 03/2013; 4(4):1687-1700. · 8.31 Impact Factor
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    ABSTRACT: The association constants for a family of 96 closely related zinc porphyrin-pyridine ligand complexes have been measured in two different solvents, toluene and 1,1,2,2-tetrachloroethane (TCE). The zinc porphyrin receptors are equipped with phenol side arms, which can form intramolecular H-bonds with ester or amide side arms on the pyridine ligands. These association constants were used to construct 64 chemical double mutant cycles, which measure the free energy contributions of intramolecular H-bonding interactions to the overall stability of the complexes. Measurement of association constants for the corresponding intermolecular H-bonding interactions allowed determination of the effective molarities (EM) for the intramolecular interactions. Comparison of ligands that feature amide H-bond acceptors and ester H-bonds at identical sites on the ligand framework show that the values of EM are practically identical. Similarly, the values of EM are practically identical in toluene and in TCE. However, comparison of two ligand series that differ by one degree of torsional freedom shows that the values of EM for the flexible ligands are an order of magnitude lower than for the corresponding rigid ligands. This observation holds for a range of different supramolecular architectures with different degrees of receptor-ligand complementarity and suggests that in general the cost of freezing a rotor in supramolecular complexes is of the order of 5 kJ/mol.
    Journal of the American Chemical Society 01/2013; · 10.68 Impact Factor
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    ABSTRACT: The host-guest chemistry of the octanuclear cubic coordination cage [Co(8)L(12)](16+) (where L is a bridging ligand containing two chelating pyrazolyl-pyridine units connected to a central naphthalene-1,5-diyl spacer via methylene "hinges") has been investigated in detail by (1)H NMR spectroscopy. The cage encloses a cavity of volume of ca. 400 Å(3), which is accessible through 4 Å diameter portals in the centers of the cube faces. The paramagnetism of the cage eliminates overlap of NMR signals by dispersing them over a range of ca. 200 ppm, making changes of specific signals easy to observe, and also results in large complexation-induced shifts of bound guests. The cage, in CD(3)CN solution, acts as a remarkably size- and shape-selective host for small organic guests such as coumarin (K = 78 M(-1)) and other bicyclic molecules of comparable size and shape such as isoquinoline-N-oxide (K = 2100 M(-1)). Binding arises from two independent recognition elements, which have been separately quantified. These are (i) a polar component arising from interaction of the H-bond accepting O atom of the guest with a convergent group of CH protons inside the cavity that lie close to a fac tris-chelate metal center and are therefore in a region of high electrostatic potential; and (ii) an additional component arising from the second aromatic ring (aromatic/van der Waals interactions with the interior surface of the cage and/or solvophobic interactions). The strength of the first component varies linearly with the H-bond-accepting ability of the guest; the second component is fixed at approximately 10 kJ mol(-1). We have also used (1)H-(1)H exchange spectroscopy (EXSY) experiments to analyze semiquantitatively two distinct dynamic processes, viz. movement of the guest into and out of the cavity and tumbling of the guest inside the host cavity. Depending on the size of the guest and the position of substituents, the rates of these processes can vary substantially, and the rates of processes that afford observable cross-peaks in EXSY spectra (e.g., between free and bound guest in some cases; between different conformers of a specific host·guest complex in others) can be narrowed down to a specific time window. Overall, the paramagnetism of the host cage has allowed an exceptionally detailed analysis of the kinetics and thermodynamics of its host-guest behavior.
    Inorganic Chemistry 01/2013; · 4.59 Impact Factor
  • Christopher A. Hunter
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    ABSTRACT: The bulk properties of liquids provide information on the thermodynamic properties of intermolecular interactions between non-polar molecules. Literature data on noble gases, alkanes and perfluorocarbons have been analysed to investigate the relationship of the magnitude of van der Waals interactions between non-polar molecules with chemical structure and molecular architecture. A molecular model of the liquid state is proposed based on the concept of a zero point void, which has a volume of 5 Å3 and a surface area of 19 Å2 per molecule. This void is the minimum volume required for each molecule to independently exchange an intermolecular contact and hence move in the liquid. Three hypothetical constructs (the zero point solid, the zero point liquid and the ideal liquid) are used to separate the processes of melting, thermal expansion and evaporation. Melting is a complex process affected by contributions from changes in structure in the solid, formation of the zero point void and thermal expansion. Evaporation involves breaking all intermolecular interactions between a molecule and the surrounding liquid and therefore provides a straightforward measure of the total van der Waals interaction. Experimental data for the enthalpy barrier to the evaporation process indicate that the total van der Waals interaction is approximately a linear function of molecular surface area, worth 0.3 kJ mol−1 Å−2 for non-polar liquids. Expansion involves breaking local intermolecular contacts and is generally associated with a substantially lower energy barrier that depends on the degree of coupling between interaction sites across the molecular surface. The expansion process is closely related to the phase changes that occur at the triple point and the critical point, and these properties are therefore a complex function of molecular architecture. Similarly, the free energy change for the vapour–liquid equilibrium depends on the molecular architecture. In contrast, transfer free energy data for liquid–liquid equilibria suggest that van der Waals interactions are a simple function of molecular surface area, independent of atom type or molecular architecture. For processes that take place within the liquid state, free energy changes due to exchange of van der Waals interactions are therefore expected to be small.
    Chemical Science 01/2013; 4(2):834-848. · 8.31 Impact Factor
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    Nikolaos Nikogeorgos, Christopher Hunter, Graham J Leggett
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    ABSTRACT: Measurements have been made of the adhesion and friction forces between organic monolayers in heptane/acetone mixtures using an atomic force microscope (AFM). It has been found that the contact mechanics are best modeled by treating the friction force as the sum of a load-dependent term (attributed to "molecular plowing") and an area-dependent term attributed to shearing (adhesion). The relative contributions of plowing and shearing are determined by the coefficient of friction, µ, and the surface shear strength τ. The transition from adhesion- to load-determined friction is controlled by the solvation state of the surface: solvated surfaces represent a limiting case in which the shear term approaches zero, and the friction-load relationship is linear, while in other circumstances, the friction-load relationship is non-linear and consistent with Derjaguin-Muller-Toporov mechanics. A striking correlation has been observed between the concentration-dependence of the association constant (Ka) for the formation of 1:1 hydrogen-bonded complexes and the pull-off force Fa and surface shear strength τ for the same molecules when one partner is immobilized by attachment to an AFM probe and the other is adsorbed to a surface. Analysis of the concentration-dependence of Fa and τ enables the prediction of KS with remarkably high precision, indicating that for these hydrogen bonding systems, the tip-sample adhesion is dominated by the H-bond thermodynamics. For mixed monolayers, H-bond thermodynamics dominate the interaction even at very low concentrations of the H-bond acceptor. Even for weakly adhering systems, a non-linear friction-load relationship results. The variation in τ with the film composition is correlated very closely with the variation in Fa. However, the coefficient of friction varies little with the film composition and is invariant with the strength of tip-sample adhesion, being dominated by molecular plowing and, for sufficiently large concentrations of hydroxyl terminated adsorbates, the disruption of intramonolayer hydrogen bonding interactions.
    Langmuir 12/2012; · 4.38 Impact Factor
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    ABSTRACT: The association constants for formation of 1:1 complexes between a H-bond acceptor, tri-n-butylphosphine oxide, and a H-bond donor, 4-phenylazophenol, have been measured in a range of different solvent mixtures. Binary mixtures of n-octane and a more polar solvent (ether, ester, ketone, nitrile, sulfoxide, tertiary amide, and halogenated and aromatic solvents) have been investigated. Similar behavior was observed in all cases. When the concentration of the more polar solvent is low, the association constant is identical to that observed in pure n-octane. Once a threshold concentration of the more polar solvent in reached, the logarithm of the association constant decreases in direct proportion to the logarithm of the concentration of the more polar solvent. This indicates that one of the two solutes is preferentially solvated by the more polar solvent, and it is competition with this solvation equilibrium that determines the observed association constant. The concentration of the more polar solvent at which the onset of preferential solvation takes place depends on solvent polarity: 700 mM for toluene, 60 mM for 1,1,2,2-tetrachloroethane, 20 mM for the ether, ester, ketone, and nitrile, 0.2 mM for the tertiary amide, and 0.1 mM for the sulfoxide solvents. The results can be explained by a simple model that considers only pairwise interactions between specific sites on the surfaces of the solutes and solvents, which implies that the bulk properties of the solvent have little impact on solvation thermodynamics.
    The Journal of Physical Chemistry B 11/2012; · 3.61 Impact Factor

Publication Stats

2k Citations
1,259.22 Total Impact Points

Institutions

  • 1993–2014
    • The University of Sheffield
      • Department of Chemistry
      Sheffield, England, United Kingdom
  • 2011
    • Birkbeck, University of London
      • Institute of Structural and Molecular Biology
      London, ENG, United Kingdom
  • 2009
    • The University of Edinburgh
      • School of Chemistry
      Edinburgh, SCT, United Kingdom
  • 2007
    • University College London
      • Department of Chemistry
      London, ENG, United Kingdom
    • The University of Manchester
      • School of Chemical Engineering and Analytical Science
      Manchester, ENG, United Kingdom
  • 2005–2006
    • Catalan Institution for Research and Advanced Studies
      Barcino, Catalonia, Spain
    • ICIQ Institute of Chemical Research of Catalonia
      Tarraco, Catalonia, Spain
  • 2000
    • University of the Balearic Islands
      • Departamento de Química
      Palma, Balearic Islands, Spain
  • 1992–1996
    • University of Otago
      • Department of Chemistry
      Taieri, Otago Region, New Zealand
  • 1991
    • University of Cambridge
      • Department of Chemistry
      Cambridge, ENG, United Kingdom