High-intensity femtosecond pulses from an X-ray free-electron laser enable pump–probe experiments for the investigation of electronic and nuclear changes during light-induced reactions. On timescales ranging from femtoseconds to milliseconds and for a variety of biological systems, time-resolved serial femtosecond crystallography (TR-SFX) has provided detailed structural data for light-induced isomerization, breakage or formation of chemical bonds and electron transfer 1 , 2 . However, all ultrafast TR-SFX studies to date have employed such high pump laser energies that nominally several photons were absorbed per chromophore 3 – 17 . As multiphoton absorption may force the protein response into non-physiological pathways, it is of great concern 18 , 19 whether this experimental approach 20 allows valid conclusions to be drawn vis-à-vis biologically relevant single-photon-induced reactions 18 , 19 . Here we describe ultrafast pump–probe SFX experiments on the photodissociation of carboxymyoglobin, showing that different pump laser fluences yield markedly different results. In particular, the dynamics of structural changes and observed indicators of the mechanistically important coherent oscillations of the Fe–CO bond distance (predicted by recent quantum wavepacket dynamics 21 ) are seen to depend strongly on pump laser energy, in line with quantum chemical analysis. Our results confirm both the feasibility and necessity of performing ultrafast TR-SFX pump–probe experiments in the linear photoexcitation regime. We consider this to be a starting point for reassessing both the design and the interpretation of ultrafast TR-SFX pump–probe experiments 20 such that mechanistically relevant insight emerges.

Using sub-20-fs ultrafast spectroscopy, we unravel high-frequency vibrational coherences during the photoinduced charge transfer in the CoFe Prussian Blue Analogue, attributed to the transient activation of a low-symmetry Jahn–Teller mode.

Water is characterized by strong intermolecular hydrogen bonds (H-bonds) between molecules. The two hydrogen atoms in one water molecule can form H-bonds of dissimilar length. Although intimately connected to water's anomalous properties, the details and the origins of the asymmetry have remained elusive. We study water's H-bonds using the O-D stretching vibrations as sensitive reporters of H-bonding of D2O and HOD in dimethylformamide. Broader inhomogeneous linewidths of the OD band of HOD compared to the symmetric and asymmetric OD stretching modes of D2O together with density functional theory calculations provide evidence for markedly anti-correlated H-bonds: water preferentially forms one weak and one strong H-bond. Coupling peaks in the spectra for D2O directly demonstrate anti-correlated H-bonds and these anti-correlations are modulated by thermal motions of water on a sub-picosecond timescale. Experimentally inferred H-bond distributions suggest that the anti-correlations are a direct consequence of the H-bonding potential of XH2 groups, which we confirm for the ND2 group of urea. These structural and dynamic insights into H-bonding are essential for understanding the relationship between the H-bonded structure and phase behavior of water.

A 'catcher' based on a revolving cylindrical collector is described. The simple and inexpensive device reduces free-jet instabilities inherent to high-viscosity extrusion injection, facilitating delivery of microcrystals for serial diffraction X-ray crystallography.

Fused polythiophenes attached to Fe( ii )NHC complexes induced a mixing of the t 2g and π HOMO orbitals promoting 80 nm red-shift of the MLCT transition, 3 fold increase of the molar extinction coefficient and 3 MLCT excited state lifetime up to 18 ps.

The amphiphilicity and denaturation efficiency of urea can be tuned via alkylation. Although the interaction of alkylureas with water and proteins has been studied in detail, hydration of 1-methylurea has remained elusive, precluding the isolation of the effect of an individual methyl group. Here, we study water dynamics in the hydration shell of 1-methylurea (1-MU) using infrared absorption and ultrafast infrared spectroscopies. We find that 1-MU hardly affects the hydrogen-bond distribution of water as probed by the OD stretching vibration of HOD molecules. Polarization resolved infrared pump-probe experiments reveal that 1-MU slows down the rotational dynamics of up to 3 water molecules in its hydration shell. A comparison to earlier results for other alkylureas suggests that further alkylation does not necessarily slow down the rotational dynamics of additional water molecules. Two-dimensional infrared experiments show that 1-MU markedly slows down the hydrogen-bond fluctuation dynamics of water, yet similar to what has been found for urea and dimethylureas. Remarkably, (alkyl-)ureas that share a similar effect on water's hydrogen-bond fluctuation dynamics have a similar (modest) protein denaturation tendency. As such, not only the hydrophobicity but also hydration of hydrophilic fragments of alkylureas may be relevant to explain their function toward biomolecules.

The upper critical solution temperature (UCST)-type liquid-liquid phase separation of imidazolium-based ionic liquids (ILs), 1-alkyl-3-methylimidazolium bis(trifluoromethanesulfonyl)imide ([Cnmim][TFSI], where n represents the alkyl chain length of the cation, n = 6, 8, 10, and 12) binary solutions with formamide (FA) was examined as a function of temperature and the FA mole fraction xFA. The two-phase region (immiscible region) of the solutions is much larger and expands more with the increase in n, in comparison with the previous [Cnmim][TFSI]-1,4-dioxane (1,4-DIO) systems. An array of spectroscopic techniques, including 1H and 13C NMR and IR combined with molecular dynamics (MD) simulations, was conducted on the present binary systems to clarify the microscopic interactions that contribute to the phase-separation mechanism. The hydrogen-bonding interactions of the imidazolium ring H atoms are more favorable with the O atoms of the FA molecules than with 1,4-DIO molecules, whereas the latter interact more favorably with the alkyl chain of the cation. Upon lowering the temperature, the FA molecules gradually self-aggregate through self-hydrogen bonding to form FA clusters. Concomitantly, clusters of ILs are formed via the electrostatic interaction between the counter ions and the dispersion force among the IL alkyl chains. Small-angle neutron scattering (SANS) experiments on the [C6mim][TFSI]-FA-d2 and [C8mim][TFSI]-FA-d2 systems revealed, similarly to [Cnmim][TFSI]-1,4-DIO systems, the crossover of the mechanism from the 3D-Ising mechanism around the UCST xFA to the mean-field mechanism at both sides of the mole fraction. Interestingly, the xFA range of the 3D-Ising mechanism for the FA systems is wider compared with the range of the 1,4-DIO systems. In this way, the self-hydrogen bonding among FA molecules most significantly governs the phase equilibria of the [Cnmim][TFSI]-FA systems.

Liquid-liquid phase separation of binary systems for imidazolium-based ionic liquids (ILs), 1-alkyl-3-methylimidazolium bis(trifluoromethanesulfonyl)imide ([Cnmim][TFSI], where n represents the alkyl chain length of the cation), with 1,4-dioxane (1,4-DIO) was observed as a function of temperature and 1,4-DIO mole fraction, x1,4-DIO. The phase diagrams obtained for [Cnmim][TFSI]-1,4-DIO systems showed that the miscible region becomes wider with an increase in the alkyl chain length, n. For n = 6 and 8, an upper critical solution temperature (UCST) was found. To clarify the mechanism of the UCST-type phase separation, small-angle neutron scattering (SANS) experiments were conducted on the [C8mim][TFSI]-1,4-DIO-d8 system at several x1,4-DIO. The critical exponents of γ and ν determined from the SANS experiments showed that phase separation of the system at the UCST mole fraction occurs via the 3D-Ising mechanism, while that on both sides of UCST occurs via the mean field mechanism. Thus, the crossover of mechanism was observed for this system. The microscopic interactions among the cation, anion, and 1,4-DIO were elucidated using 1H and 13C NMR and IR spectroscopic techniques, together with the theoretical method of molecular dynamics (MD) simulations. The results on the microscopic interactions suggest that 1,4-DIO molecules cannot strongly interact with H atoms on the imidazolium ring, while they interact with the octyl chain of the cation through dispersion force. With a decrease in temperature, 1,4-DIO molecules gradually aggregate to form 1,4-DIO clusters in the binary solutions. The strengthening of the C-H⋯O interaction between 1,4-DIO molecules by cooling is the key to the phase separation. Of course, the electrostatic interaction between the cations and anions results in the formation of IL clusters. When IL clusters are excluded from 1,4-DIO clusters, liquid-liquid phase separation occurs. Accordingly, the balance between the electrostatic force between the cations and anions and the C-H⋯O interaction between the 1,4-DIO determines the 3D-Ising or the mean field mechanism of phase separation.

Ionic liquids (IL), being low-temperature melts by their nature, are of considerable scientific interest due to a number of their unique properties. The practical application of ILs, especially in electrochemistry, has significantly expanded due to the use of mixtures with molecular solvents of various natures. A detailed microscopic description of the local structure in such systems, depending on the nature of its constituent components and the composition of the mixture, remains an urgent problem of modern chemistry of liquid state. In this chapter, we review the results obtained by vibration spectroscopy and NMR chemical shift on the variations in microscopic structure as a function of mixture composition. We point out the controversy about the assignment of the imidazolium C–H stretching vibration mode and systemized its red shift as associated with the outcome of the competition of the solvent molecules and the anions for the C–H bond. Furthermore, the introduction of the double difference relative chemical shift helps us to compare and rationalize the 1H chemical shift literature data obtained in various ionic liquid/solvent mixtures. The most significant changes in the 1H chemical shift occur at low ionic liquid content. Dilution and stacking interactions between the cation rings induce a negative variation of the 1H relative chemical shift. As the solvent and the ions can establish hydrogen bond interactions, when these interactions are weaker, almost equal or higher than the interionic interactions, this results in negative, almost equal to zero, or positive values of the relative chemical shift, respectively. Moreover, starting from the idea that the nearest neighbor anions or solvent molecules of the C–H bond are strongly influencing the associated C–H vibration mode and the 1H chemical shift, we used molecular dynamic simulation and the nearest neighbor approach to calculate radial distribution and spatial radial distribution functions, and to define two statistical distance descriptors of the hydrogen bond structure C–H… X ( X being atom of either the anion or of the solvent) to characterize the local structure around the C–H bond of the cation. The mole fraction dependence of these statistical properties, calculated by taking only the nearest neighbor into account, correlates consistently with spectroscopic data. Indeed, these descriptors are relatively unaffected in the ionic liquid mole fraction (xIL) range between 1.0 and 0.3, while with a further decrease of xIL a large effect on these descriptors is observed. These changes are compatible with the physical picture that the solvent molecules compete with the anions to occupy positions close to the cation ring hydrogen atoms. They are associated with the expected weakening of the cation–anion interactions in the chosen solvents. These results are in good agreement with the behavior of the 1H chemical shift and the C–H vibration mode as a function of xIL. Furthermore, the results of the MD simulations point out the importance of the anion—solvent interactions in weakening the interionic ones.

In recent years the interaction of organophosphates and imines, which is at the core of Brønsted acid organocatalysis, has been established to be based on strong ionic hydrogen bonds. Yet, besides the formation of homodimers consisting of two acid molecules and heterodimers consisting of one acid and one base, also multimeric molecular aggregates are formed in solution. These multimeric aggregates consist of one base and several acid molecules. The details of the intermolecular bonding in such aggregates, however, have remained elusive. To characterize composition-dependent bonding and bonding dynamics in these aggregates, we use linear and nonlinear infrared (IR) spectroscopy at varying molar ratios of diphenyl phosphoric acid and quinaldine. We identify the individual aggregate species, giving rise to the structured, strong, and very broad infrared absorptions, which span more than 1000 cm–1. Linear infrared spectra and density functional theory calculations of the proton transfer potential show that doubly ionic intermolecular hydrogen bonds between the acid and the base lead to absorptions which peak at ∼2040 cm–1. The contribution of singly ionic hydrogen bonds between an acid anion and an acid molecule is observed at higher frequencies. As common to such strong hydrogen bonds, ultrafast IR spectroscopy reveals rapid, ∼ 100 fs, dissipation of energy from the proton transfer coordinate. Yet, the full dissipation of the excess energy occurs on a ∼0.8–1.1 ps time scale, which becomes longer when multimers dominate. Our results thus demonstrate the coupling and collectivity of the hydrogen bonds within these complexes, which enable efficient energy transfer.

The mixing states of an imidazolium-based ionic liquid (IL), 1-butyl-3-methylimidazolium bis(trifluoromethanesulfonyl)imide ([C4mim][TFSI]), with cycloethers, tetrahydrofuran (THF), 1,4-dioxane (1,4-DIO), and 1,3-dioxane (1,3-DIO), have been clarified on the meso- and microscopic scales using small-angle neutron scattering (SANS), IR, and NMR experiments and molecular dynamics (MD) simulations. SANS profiles of [C4mim][TFSI]-THF-d8 and -1,4-DIO-d8 solutions at various mole fractions xML of molecular liquid (ML) have shown that [C4mim][TFSI] is heterogeneously mixed with THF and 1,4-DIO on the mesoscopic scale, to a high extent in the case of the latter solution. In fact, [C4mim][TFSI] and 1,4-DIO are not miscible with each other above the 1,4-DIO mole fraction x1,4-DIO of 0.903, whereas the IL can be mixed with THF over the entire range of THF mole fraction xTHF. The results of IR and 1H and 13C NMR measurements and MD simulations showed that cycloether molecules are more strongly hydrogen-bonded with the imidazolium ring H atoms in the order of THF > 1,3-DIO > 1,4-DIO. Although 1,4-DIO and 1,3-DIO molecules are structural isomers, our results point out that 1,4-DIO cannot be strongly hydrogen-bonded with the ring H atoms. The solvation of [TFSI]- by cycloethers through the dipole-dipole interaction promotes hydrogen bonding between the ring H atoms and cycloethers. Thus, 1,4-DIO with the lowest dipole moment cannot easily eliminate [TFSI]- from the imidazolium ring. This results in the weakest hydrogen bonds of 1,4-DIO with the ring H atoms. 2D-NMR of 1H{1H} rotating-frame nuclear Overhauser effect spectroscopy (ROESY) showed the interaction of the three cycloethers with the butyl group of [C4mim]+. 1,4-DIO mainly interacts with the butyl group by the dispersion force, whereas THF interacts with the IL by both hydrogen bonding and dispersion force. This leads to the higher heterogeneity of the 1,4-DIO solutions compared to the THF solutions.

The control of ligand-field splitting in iron (II) complexes is critical to slow down the metal-to-ligand charge transfer (MLCT)-excited states deactivation pathways. The gap between the metal-centered states is maximal when the coordination sphere of the complex approaches an ideal octahedral geometry. Two new iron(II) complexes (C1 and C2), prepared from pyridylNHC and pyridylquinoline type ligands, respectively, have a near-perfect octahedral coordination of the metal. The photophysics of the complexes have been further investigated by means of ultrafast spectroscopy and TD-DFT modeling. For C1, it is shown that—despite the geometrical improvement—the excited state deactivation is faster than for the parent pseudo-octahedral C0 complex. This unexpected result is due to the increased ligand flexibility in C1 that lowers the energetic barrier for the relaxation of 3MLCT into the 3MC state. For C2, the effect of the increased ligand field is not strong enough to close the prominent deactivation channel into the metal-centered quintet state, as for other Fe-polypyridine complexes.

Alkylated ureas are frequently used amphiphiles to mediate biomolecule water interactions, yet their hydrophobic substitution pattern critically affects their function. These differences can be traced back to their hydration, which is poorly understood. Here, we investigate subtle effects of the hydrophobic pattern of ureas on hydration dynamics using a combination of linear and non-linear infrared spectroscopies on the OD stretching vibration of HDO. Isomeric 1,3-dimethylurea (1,3-DMU), 1,1-dimethylurea (1,1-DMU) and 1-ethylurea (1-EU) exhibit very similar and rather weak modulation of the water hydrogen-bond strength distribution. Yet, only 1,3-DMU and 1,1-DMU enhance the hydrogen-bond heterogeneity and slow-down its fluctuation dynamics. In turn, rotational dynamics of water molecules, which is dominated by hydrogen bond switches, is significantly impeded in the presence of 1,3-DMU and only weakly by 1,1-DMU and 1-EU. These marked differences can be explained by both excluded volume effects in hydration and self-aggregation, which may be the key to their biotechnological function.

The aim of this paper is to quantify the changes of the interionic and ion-solvent interactions in mixtures of imidazolium-based ionic liquids, having tetrafluoroborate (BmimBF4), hexafluorophosphate (BmimPF6), trifluoromethylsulfonate (BmimTFO), or bis(trifluoromethanesulfonyl)imide (BmimTFSI), anions, and polar aprotic molecular solvents, such as acetonitrile (AN), γ-butyrolactone (GBL), and propylene carbonate (PC). For this purpose, we calculate, using the nearest-neighbor approach, the average distance between the imidazolium ring H atom in positions 2, 4, and 5 (H2,4,5) and the nearest high-electronegativity atom of the solvent or anion (X) as distance descriptors, and the mean angle formed by the C2,4,5-H2,4,5 bond and the H2,4,5···X axis around the H2,4,5 atom as angular descriptors of the cation-anion and cation-solvent interactions around the ring C-H groups. The behavior of these descriptors as a function of the ionic liquid mole fraction is analyzed in detail. The obtained results show that the extent of the change of these descriptors with respect to their values in the neat ionic liquid depends both on the nature of the anion and on the mixture composition. Thus, in the case of the mixtures of the molecular solvents with BmimBF4 and BmimTFO, a small change of the distance and a drastic increase of the angular descriptor corresponding to the cation-anion interactions are observed with decreasing mole fraction of the ionic liquid, indicating that the anion moves from the above/below position (with respect to the imidazolium ring plane) to a position that is nearly linearly aligned with the C2-H2 bond and hinders the possible interaction between the C2-H2 group and the solvent molecules. On the other hand, in the case of mixtures of BmimTFSI and BmimPF6 with the molecular solvents, both the observed increase of the distance descriptor and the slight change of the angular descriptor with decreasing ionic liquid mole fraction are compatible with the direct interactions of the solvent with the C2-H2 group. The behavior of these descriptors is correlated with the experimentally observed 1H chemical shift of the C2-H2 group and the red shift of the C2-H2 vibrational mode, particularly at low ionic liquid mole fractions. The present results are thus of great help in interpreting these experimental observations.

The catalytic efficiency of diol-based organocatalysts has been shown to strongly depend on the diols molecular structure including hydrogen-bonding, yet, the underlying molecular-level origins have remained elusive. Herein a study on the inter- and intramolecular hydrogen-bonding of two isomeric diol-based catalysts (TADDOLs) in solution is presented: 1-Naphthyl substituted TADDOL (1nTADDOL), which exhibits high catalytic efficiency, and 2-naphthyl substituted TADDOL (2nTADDOL), which is a poor catalyst. Using nuclear magnetic resonance and infrared spectroscopy, comparable hydrogen-bond strengths for both TADDOLs in solution were found, however, significantly slower bonding dynamics for 1nTADDOL. In aromatic solvents, 1nTADDOL forms less, but longer-lived, intermolecular OH...pi bonds to solvent molecules, as compared to 2nTADDOL. Thus, rather than previously suggested differences in intermolecular hydrogen-bonding strengths, the results suggest that the hydrogen-bonding kinetics and entropies differ for both TADDOLs, which also explains their vastly different catalytic activities.

Myeloid cell leukemia-1 (Mcl-1) is an anti-apoptotic member of the Bcl-2 family proteins. Its amplification is one of the most frequent genetic aberrations found in human cancers. Pyridoclax, a promising BH3 mimetic inhibitor, interacts directly with Mcl-1 and induces massive apoptosis at a concentration of 15 mu M in combination with anti-Bcl-x(L) strategies in chemo-resistant ovarian cancer cell lines. In this study, a combined experimental and theoretical approach was used to investigate the binding mode of Pyridoclax to Mcl-1. The representative poses generated from dynamics simulations compared with NMR data revealed: (i) Pyridoclax bound to P1 and P2 pockets of Mcl-1 BH3 binding groove through its styryl and methyl groups establishing mainly hydrophobic contacts, (ii) one of the ending pyridines interacts through electrostatic interaction with K234 side chain, a negatively charged residue present only in this position in Mcl-1.

The hydrogen bonds of the imidazolium-ring H atoms of ionic liquids (ILs), 1-alkyl-3-methylimidazolium bis(trifluoromethylsulfonyl)amides ([Cnmim][TFSA], n = 2 to 12 where n represents the alkyl chain length), with the O atom of dimethyl sulfoxide (DMSO) have been elucidated using 1H, 13C, and 15N NMR spectroscopy and soft X-ray absorption and emission spectroscopy (XAS and XES). Density functional theory (DFT) calculations have been performed on an isolated DMSO molecule and two cluster models of [Cnmim]+-DMSO by hydrogen bonding to interpret the XES spectra for the [Cnmim][TFSA]-DMSO solutions. The 1H and 13C NMR chemical shifts of the imidazolium ring showed that deshielding of the ring H and C atoms is moderate as the DMSO mole fraction xDMSO increases to ∼0.8; however, it becomes more significant with further increase of xDMSO. This finding suggests that the hydrogen bonds of the three ring H atoms with the DMSO O atoms are saturated in solutions with xDMSO increased to ∼0.8. The 1H and 13C chemical shifts of the alkyl chains revealed that the electron densities of the chain H and C atoms gradually decrease with increasing xDMSO, except for the N1-bound carbon atom C7 of the chain. The 15N NMR chemical shifts showed that the imidazolium-ring N1 atom which is bound to the alkyl chain is shielded with increasing xDMSO in the range from 0 to 0.8 and is then deshielded with further increase of xDMSO. In contrast, the imidazolium ring N3 atom is simply deshielded with increasing xDMSO. Thus, the electron densities of the alkyl chain may be condensed at the C7 and N1 atoms of [Cnmim]+ by the hydrogen bonding of the ring H atoms with DMSO. The hydrogen bonding of DMSO with the ring results in low-energy shifts of the XES peaks of the O K-edge of DMSO. Small-angle neutron scattering experiments showed that [Cnmim][TFSA] and DMSO are homogeneously mixed with each other on the mesoscopic scale. This results from the strong hydrogen bonds of DMSO with the imidazolium-ring H atoms.

The changes of the local structure in the binary mixture of 1-butyl-3-methylimidazolium hexafluorophosphate (BmimPF6) ionic liquid and acetonitrile are investigated over the entire composition range. Two charge distribution models of the ions are considered: in the first one, the atomic fractional charges of the cations and anions are kept equal with those in the neat ionic liquid, and hence they are independent from the mole fraction of the ionic liquid, while in the second one the charge distribution is scaled up by a mole fraction dependent factor. The sum of these charges converge to +1e and -1e on the cation and anion, respectively, at infinite dilution. All the other interactions and geometry parameters of the ions (i.e., Lennard-Jones, bond stretching, angle bending and dihedral parameters) are identical in the two cases. The effect of the fractional charge distribution on the hydrogen bonding between the counterions themselves and between the ions and solvent molecules, as well as on the stacking interactions between the cations, is analyzed. To this end, two distances, characteristic of the hydrogen bond formed by the donor moiety and its nearest neighbor acceptor, as well as a coordinate system that defines unambiguously the orientation between a reference cation and its nearest neighbor, are introduced. It is shown that, with the variable charge model, the neighboring cation-anion pairs maintain their relative arrangement similar to the neat ionic liquid down to an ionic liquid mole fraction of xIL = 0.10, whereas in the case of the constant charge model such changes occur already at xIL = 0.20. Furthermore, the analysis of the first and the second nearest neighbor distance distributions of an anion around a reference cation indicates that, at this mole fraction range, there are two different preferred arrangements of the anions around the cations. In the first one, similarly to the local structure around a reference cation in the neat ionic liquid, the anion forms a distorted hydrogen bond with the cation, while in the second one the anion is located farther from the cation, forming no hydrogen bond with it. The relative population of these two types of preferred nearest neighbor cation-anion arrangements is found to be sensitive to further decrease of the ionic liquid mole fraction. These findings correlate with experimental results concerning the behavior of many physical chemical properties (e.g., excess volume, excess viscosity, chemical shift, infrared and Raman vibrational mode shifts, diffusion, etc.) that were found to undergo a drastic change in this mole fraction range. Our results show that in this composition range a transition occurs from the situation where the macroscopic physical chemical properties of the system are determined primarily by the cation-anion hydrogen bonding interactions to that where they are determined by the solvation of the cation and the anion by the molecular solvent.

Ion-protein interactions are important for protein function, yet challenging to rationalize owing to the multitude of possible ion-protein interactions. To explore specific ion effects on protein binding sites, we investigate the interaction of different salts with the zwitterionic peptide triglycine in solution. Dielectric spectroscopy shows that salts affect the peptide's reorientational dynamics, with a more pronounced effect for denaturing cations (Li+ , guanidinium (Gdm+ )) and anions (I- , SCN- ) than for weakly denaturing ones (K+ , Cl- ). The effects of Gdm+ and Li+ were found to be comparable. Molecular dynamics simulations confirm the enhanced binding of Gdm+ and Li+ to triglycine, yet with a different binding geometry: While Li+ predominantly binds to the C-terminal carboxylate group, bidentate binding to the terminus and the nearest amide is particularly important for Gdm+ . This bidentate binding markedly affects peptide conformation, and may help to explain the high denaturation activity of Gdm+ salts.