Correlated proton dynamics in hydrogen bonding networks: the benchmark case of 3-hydroxyglutaric acid.

Proton and hydrogen-bonded networks sustain a broad range of structural and charge transfer processes in supramolecular materials. The modelling of proton dynamics is however challenging and demands insights from prototypical benchmark systems. The intramolecular H-bonding networks induced by either protonation or deprotonation of 3-hydroxyglutaric acid provide intriguing case studies of correlated proton dynamics. The vibrational signatures associated with the fluxional proton bonding and its coupling with the hydroxyglutaric backbone are investigated here with infrared action ion spectroscopy experiments and Born-Oppenheimer molecular dynamics (BOMD) computations. Despite the formally similar symmetry of protonated and deprotonated hydroxyglutaric acid, the relative proton affinities of the oxygen centers of the carboxylic and carboxylate groups with respect to that of the central hydroxyl group lead to distinct proton dynamics. In the protonated acid, a tautomeric arrangement of the type HOCO·[HOH]+·OCOH is preferred with the proton binding tighter to the central hydroxyl moiety and the electronic density being shared between the two nearly symmetric H-bonds with the carboxylic end groups. In the deprotonated acid, the asymmetric [OCO]-·HO·HOCO configuration is more stable, with a stronger H-bonding on the bare carboxylate end. Both systems display active backbone dynamics and concerted Grothuss-like proton motions, leading to diffuse band structures in their vibrational spectra. These features are accurately reproduced by the BOMD computations.

Wetting of a Hydrophobic Surface: Far-IR Action Spectroscopy and Dynamics of Microhydrated Naphthalene.

The interaction of water and polycyclic aromatic hydrocarbons is of fundamental importance in areas as diverse as materials science and atmospheric and interstellar chemistry. The interplay between hydrogen bonding and dipole-π interactions results in subtle dynamics that are challenging to describe from first principles. Here, we employ far-IR action vibrational spectroscopy with the infrared free-electron laser FELIX to investigate naphthalene with one to three water molecules. We observe diffuse bands associated with intermolecular vibrational modes that serve as direct probes of the loose binding of water to the naphthalene surface. These signatures are poorly reproduced by static DFT or Møller-Plesset computations. Instead, a rationalization is achieved through Born-Oppenheimer Molecular Dynamics simulations, revealing the active mobility of water over the surface, even at low temperatures. Therefore, our work provides direct insights into the wetting interactions associated with shallow potential energy surfaces while simultaneously demonstrating a solid experimental-computational framework for their investigation.

Nucleation of zeolitic imidazolate frameworks: from molecules to nanoparticles.

We have studied the clusters involved in the initial stages of nucleation of Zeolitic Imidazolate Frameworks, employing a wide range of computational techniques. In the pre-nucleating solution, the prevalent cluster is the ZnIm4 cluster (formed by a zinc cation, Zn2+, and four imidazolate anions, Im-), although clusters such as ZnIm3, Zn2Im7, Zn2Im7, Zn3Im9, Zn3Im10, or Zn4Im12 have energies that are not much higher, so they would also be present in solution at appreciable quantities. All these species, except ZnIm3, have a tetrahedrally coordinated Zn2+ cation. Small ZnxImy clusters are less stable than the ZnIm4 cluster. The first cluster that is found to be more stable than ZnIm4 is the Zn41Im88 cluster, which is a disordered cluster with glassy structure. Bulk-like clusters do not begin to be more stable than glassy clusters until much larger sizes, since the larger cluster we have studied (Zn144Im288) is still less stable than the glassy Zn41Im88 cluster, suggesting that Ostwald's rule (the less stable polymorph crystallizes first) could be fulfilled, not for kinetic, but for thermodynamic reasons. Our results suggest that the first clusters formed in the nucleation process would be glassy clusters, which then undergo transformation to any of the various crystal structures possible, depending on the kinetic routes provided by the synthesis conditions. Our study helps elucidate the way in which the various species present in solution interact, leading to nucleation and crystal growth.

A Dynamic Proton Bond: MH+·H2O ⇌ M·H3O+ Interconversion in Loosely Coordinated Environments.

The interaction of organic molecules with oxonium cations within their solvation shell may lead to the emergence of dynamic supramolecular structures with recurrently changing host-guest chemical identity. We illustrate this phenomenon in benchmark proton-bonded complexes of water with polyether macrocyles. Despite the smaller proton affinity of water versus the ether group, water in fact retains the proton in the form of H3O+, with increasing stability as the coordination number increases. Hindrance in many-fold coordination induces dynamic reversible (ether)·H3O+ ⇌ (etherH+)·H2O interconversion. We perform infrared action ion spectroscopy over a broad spectral range to expose the vibrational signatures of the loose proton bonding in these systems. Remarkably, characteristic bands for the two limiting proton bonding configurations are observed in the experimental vibrational spectra, superimposed onto diffuse bands associated with proton delocalization. These features cannot be described by static equilibrium structures but are accurately modeled within the framework of ab initio molecular dynamics.

Insights into the binding of arginine to adenosine phosphate from mimetic complexes.

The amino acid arginine plays a key role in the interaction of proteins with adenosine phosphates, as its protonated guanidinium side group is capable of building multipodal H-bonding interactions with the oxygen atoms of the phosphate, phosphoester and ribose moieties and with the nitrogen atoms of adenine. Protein interactions often take place in competition with other ionic species, typically metal cations, which are prone to build concerted coordination arrangements with the same centers of negative charge as guanidinium. We report on a vibrational spectroscopy and computational investigation of a positively charged ternary complex formed by adenosine monophosphate (AMP) with methyl guanidinium and Na+. Following a bottom-up approach, an analogous complex with ribose phosphate is characterized as well, which serves to assess the individual role of the phosphate, sugar and adenine moieties in the binding process and to compare, within a single complex, the interactions associated with diffuse versus localized charge distributions of guanidinium and the alkali cation, respectively. The results indicate that Na+ is preferentially hosted in a semi-rigid pocket formed by the phosphoester-adenosine backbone of AMP and displaces guanidinium to a peripheral binding to the phosphate anionic end group. This suggests that the control of the salt concentration may constitute an effective route to modulate protein-AMP complexation.

Inclusion complexes of the macrocycle nonactin with benchmark protonated amines: aniline and serine.

The biological activity of the macrocycle nonactin is intimately related to its ionophore properties and ability to act as a selective cation carrier. While the focus of most investigations on nonactin has been on the binding of metal cations and small molecular ions, this study pursues the characterization of its inclusion complexes with primary amines with bulky structured side groups of different polarity. To this end, the complexes of nonactin with aniline and with the amino acid L-serine, both in protonated form, are considered as case studies and their relevant coordination arrangements are assessed by means of infrared action spectroscopy, quantum chemical density functional theory and Born-Oppenheimer molecular dynamics. The study suggests that the oxygen atoms from the oxolane (tetrahydrofuran) groups of nonactin constitute the preferential docking sites of the ammonium moiety of the guest cation, although conformational constraints promote interactions with the ester carbonyl backbone groups. In the aniline complex, the benzyl side ring is oriented outwards from the cavity, whereas in the case of L-serine, the side carboxylic acid and alcohol groups participate actively in the coordination process. Interestingly, the accommodation of L-serine is favoured when nonactin adopts an enantiomeric-selective folding, that promotes the tripodal coordination of the protonated amine group with oxolane rings from three nonactinic acid blocks with enantiomeric sequence (+)-(-)-(+), which allows for a facile coordination of the serine side groups. This is recognized as a general feature associated with the alternation of chiral domains in globally achiral natural nonactin, yielding mirror-symmetric complexes with the enantiomers of chiral amines.

Proton in the ring: spectroscopy and dynamics of proton bonding in macrocycle cavities.

The proton bond is a paradigmatic quantum molecular interaction and a major driving force of supramolecular chemistry. The ring cavities of crown ethers provide an intriguing environment, promoting competitive proton sharing with multiple coordination anchors. This study shows that protons confined in crown ether cavities form dynamic bonds that migrate to varying pairs of coordinating atoms when allowed by the flexibility of the macrocycle backbone. Prototypic native crown ethers (12-crown-4, 15-crown-5 and 18-crown-6) and aza-crown ethers (cyclen, 1-aza-18-crown-6 and hexacyclen) are investigated. For each system, Infrared action spectroscopy experiments and ab initio Molecular Dynamics computations are employed to elucidate the structural effects associated with proton diffusion and its entanglement with the conformational and vibrational dynamics of the protonated host.

Tailoring the phase diagram of discotic mesogens.

The computational modelling of discotic molecules is a central topic in colloid science that is key for the smart design of a broad range of modern functional materials. This work lays out a versatile interaction model capable of exposing the rich mesogenic behaviour of discotics. A single coarse-grained spheroplatelet core framework is employed to generate a variety of pair interaction anisotropy classes, favouring specific relative orientations of the particles (stacked, side-side, crossed, T-shaped). This paves the way for the systematic tailoring of the discotic liquid phase diagram. Monte Carlo simulations are performed for an ensemble of case studies to illustrate the correlation between the topology of the interaction and the formation of stable nematic, smectic and columnar phases, as well as of less common cubatic, uniaxial and biaxial columnar domains.

Molecular Characterization of Nonvolatile Fractions of Algerian Petroleum with High-Resolution Mass Spectrometry.

Algerian crude oil displays a marked propensity for asphaltene precipitation, leading to solid deposits during extraction, transportation, and storage. The relationship between precipitation and chemical composition is unclear; in fact, Algerian crude oil actually features a low asphaltene concentration, despite its relatively large rate of deposit formation. The rationalization of the precipitation process and its remediation should benefit from a molecular characterization of the crude oil. In this study, two unstable asphaltene fractions (A1 and A2) from two different deposits, and two resin crude oil fractions (R1 and R2) from the Hassi-Messaoud Algerian field have been characterized at the molecular level by means of high-resolution mass spectrometry with an Atmospheric Pressure Chemical Ionization (APCI) source. Positively and negatively charged compounds with molecular weights 200-1200 m/z were detected. Several thousand molecular stoichiometries were identified and classified for each sample, in terms of heteroatom content and aromaticity, searching for trends characteristic of the two asphaltenes and of the associated resins. The A2 asphaltene, from a downstream storage tank, displays a higher aromaticity and O-heteroatom content, which correlates with an enhanced aggregation propensity, in comparison to the A1 fraction, collected at the well bore. The resin fractions are found to be abundant in aliphatic hydrocarbons and heteroatomic compounds of moderate aromaticity. The more polar resin fraction, R2, is enriched in N-containing species, with respect to the less polar resin fraction R1, which correlates with the stabilizing function observed in previous works. The results stress the view of crude oil fractions as complex mixtures, rather than in terms of average prototypical compounds, when facing the understanding of asphaltene deposition conditions.

Multipodal coordination and mobility of molecular cations inside the macrocycle valinomycin.

The macrocycle valinomycin displays an outstanding ability in cation binding and carriage across hydrophobic environments (e.g., cell membranes) and constitutes a central landmark for the design of novel ionophores for the regulation of biochemical processes. Most previous investigations have focused on the capture of metal cations (primarily K+). Here, we address the versatility of valinomycin in the encapsulation of molecular ions of small and moderate size, with NH4+ and H4PO4+ as case studies. A combination of infrared action vibrational spectroscopy and quantum chemical computations of molecular structure and dynamics is employed with the two-fold aim of assessing the dominant H-bonding coordination networks in the complexes and of characterizing the positional and rotational freedom of the guest cations inside the cavity of the macrocycle. Valinomycin binds NH4+ with only moderate distortion of the C3 configuration adopted in the complexes with the metal cations. The ammonium cation occupies the center of the cavity and displays two low-energy coordination arrangements that are dynamically connected through a facile rotation of the cation. The inclusion of the bulkier phosphoric acid cation demands significant stretching of the valinomycin backbone. Interestingly, the H4PO4+ cation achieves ample positional and rotational mobility inside valinomycin. The valinomycin backbone is capable of adopting barrel-like configurations when the cation occupies a region close to the center of the cavity, and funnel-like configurations when it diffuses to positions close to the exit face. This can accommodate the cation in varying coordination arrangements, characterized by different H-bonding between the four POH arms and the ester carbonyl groups of the macrocycle.

Insights into the Recognition of Phosphate Groups by Peptidic Arginine from Action Spectroscopy and Quantum Chemical Computations.

The side group of the amino acid arginine is typically in its guanidinium protonated form under physiological conditions and participates in a broad range of ligand binding and charge transfer processes of proteins. The recognition of phosphate moieties by guanidinium plays a particularly key role in the interactions of proteins with ATP and nucleic acids. Moreover, it has been recently identified as the driving force for the inhibition of kinase phosphorilation activity by guanidinium derivatives devised as potential anticancer agents. We report on a fundamental investigation of the interactions and coordination arrangements formed by guanidinium with phosphoric, phosphate, and pyrophosphate groups. Action vibrational spectroscopy and ab initio quantum chemical computations are employed to characterize the conformations of benchmark positively charged complexes isolated in an ion trap. The multidentate structure of guanidinium and of the phosphate groups gives rise to a rich conformational landscape with a particular relevance of tweezer-like configurations, where phosphate is effectively trapped by two guanidinium cations. The pyrophosphate complex incorporates a Na+ cation, which serves to compare the interactions associated with the localized versus diffuse charge distributions of the alkali cation and guanidinium, respectively, within a common supramolecular framework.

A Cl- Hinge for Cyclen Macrocycles: Ionic Interactions and Tweezer-Like Complexes.

The supramolecular networks derived from the complexation of polyazamacrocycles with halide anions constitute fundamental building blocks of a broad range of modern materials. This study provides insights into the conformational framework that supports the binding of protonated cyclen macrocyles (1,4,7,10-Tetraazacyclododecane) by chloride anions through NHδ+···Cl- interactions. The isolated complex comprised of two cyclen hosts linked by one Cl- anion is characterized by means of infrared action spectroscopy and ion mobility mass spectrometry, in combination with quantum chemical computations. The Cl- anion is found to act as a hinge that bridges the protonated NH 2 + moieties of the two macrocycles leading to a molecular tweezer configuration. Different types of conformations emerge, depending on whether the trimer adopts an open arrangement, with significant freedom for internal rotation of the cyclen moieties, or it locks in a folded conformation with intermolecular H-bonds between the two cyclen backbones. The ion mobility collision cross section supports that folded configurations of the complex are dominant under isolated conditions in the gas phase. The IRMPD spectroscopy experiments suggest that two qualitatively different families of folded conformations coexist at room temperature, featuring either peripheral or inner positions of the anion with respect to the macrocycle cavities, These findings should have implications in the growth of extended networks in the nanoscale and in sensing applications.

Preferential host-guest coordination of nonactin with ammonium and hydroxylammonium.

The biological activity of the macrocycle nonactin is intimately related to its ionophore properties and ability to act as a selective cation carrier. The competitive binding of small protonated amines constitutes a particularly key issue in the biochemistry of nonactin, which finds application in sensing and extraction technologies. In this study, isolated complexes of nonactin with ammonium and hydroxylammonium are investigated with infrared action spectroscopy and quantum chemical computations. The focus of the investigation is on the coordination achieved by the protonated guest with the oxygen atoms of either the oxolane groups or the carboxyl groups in the ester linkages of the macrocyle host and their relative contributions to the stability of the complexes. The experimental and computational data converge to a preferred coordination arrangement associated with a tight binding of the N-H δ+ bonds with the oxolane groups. In the N H 4 + complex, this results in a compact complex of S 4 symmetry. In contrast, symmetry is disrupted in the NH3OH+ complex, as it incorporates a bifurcated coordination of the -OH bond with a carbonyl group and an oxolane group of the host, involving also a more stretched arrangement of the nonactin backbone. These gas-phase conformations are in agreement with the structures postulated for these complexes in condensed phases, from previous Raman and crystallographic experiments.

Complexes of Crown Ether Macrocycles with Methyl Guanidinium: Insights into the Capture of Charge in Peptides.

Crown ethers are well known as modulating agents of protein function and interactions. The action of crown ethers is driven by an alteration of the charged moieties of proteins through the capping of cationic amino acid side chains. This study evaluates the conformational features involved in the binding of crown ethers to the side chain of arginine. For this purpose, isolated complexes of methyl guanidinium with 12-crown-4 and 18-crown-6 are characterized with infrared action vibrational spectroscopy and quantum chemical computations. The conformational landscapes of the two complexes comprise an extensive ensemble of conformations close in energy. In the 12-crown-4 complex, the crown ether has the plane of its backbone approximately perpendicular to that of the guanidinium moiety and coordinates to two or three of its NHδ+ bonds. In the 18-crown-6 complex, the crown ether backbone is partially folded and tilted with respect to guanidinium and fixes its position in order to facilitate up to a four-fold coordination in the complex. The access of the complexes to multiple conformations leads to broad band structures in the N-H stretching region of their vibrational spectra.

Stability of proton-bound clusters of alkyl alcohols, aldehydes and ketones in Ion Mobility Spectrometry.

Significant substances in emerging applications of ion mobility spectrometry such as breath analysis for clinical diagnostics and headspace analysis for food purity include low molar mass alcohols, ketones, aldehydes and esters which produce mobility spectra containing protonated monomers and proton-bound dimers. Spectra for all n- alcohols, aldehydes and ketones from carbon number three to eight exhibited protonated monomers and proton-bound dimers with ion drift times of 6.5-13.3 ms at ambient pressure and from 35° to 80 °C in nitrogen. Only n-alcohols from 1-pentanol to 1-octanol produced proton-bound trimers which were sufficiently stable to be observed at these temperatures and drift times of 12.8-16.3 ms. Polar functional groups were protected in compact structures in ab initio models for proton-bound dimers of alcohols, ketones and aldehydes. Only alcohols formed a V-shaped arrangement for proton-bound trimers strengthening ion stability and lifetime. In contrast, models for proton-bound trimers of aldehydes and ketones showed association of the third neutral through weak, non-specific, long-range interactions consistent with ion dissociation in the ion mobility drift tube before arriving at the detector. Collision cross sections derived from reduced mobility coefficients in nitrogen gas atmosphere support the predicted ion structures and approximate degrees of hydration.

Intra-cavity proton bonding and anharmonicity in the anionophore cyclen.

Proton bonding drives the supramolecular chemistry of a broad range of materials with polar moieties. Proton delocalization and electronic charge redistribution have a profound impact on the structure of proton-bound molecular frameworks, and pose fundamental challenges to quantum chemical modelling. This study provides insights into the structural and spectral signatures of the intramolecular proton bond formed in a benchmark polyazamacrocycle anionophore (cyclen, 1,4,7,10-tetraazacyclododecane). Infrared action spectroscopy is employed to characterize the macrocycle, isolated in protonated form. In its most stable configuration, protonated cyclen adopts an open arrangement of Cs symmetry with a particularly strong NHδ+N bond across the cavity. The quantum chemical analysis of the infrared spectrum reveals intrinsic difficulties for the accurate description of the vibrational modes of the system. The reconciliation of the computational predictions with experiment demands a careful anharmonic treatment of the proton motion, which exposes the limitations of current methods. Best results are obtained with the incorporation of anharmonicity only to the fundamental modes directly related to motions of the proton. However, the full anharmonic treatment of the system fails to describe correctly the vibrations related to the macrocycle backbone. The results should serve as motivation for new developments in the modelling of proton bonded systems.

Guanidinium/ammonium competition and proton transfer in the interaction of the amino acid arginine with the tetracarboxylic 18-crown-6 ionophore.

The recognition of arginine plays a central role in modern proteomics and genomics. Arginine is unique among natural amino acids due to the high basicity of its guanidinium side chain, which sustains specific interactions and proton exchange biochemical processes. The search for suitable macrocyclic ionophores constitutes a promising route towards the development of arginine receptors. This study evaluates the conformational features involved in the binding of free arginine by the polyether macrocycle (18-crown-6)-tetracarboxylic acid. Infrared action vibrational spectroscopy and quantum-chemical computations are combined to characterize the complexes with net charges +1 and +2. The spectrum of the +1 complex can be explained in terms of a configuration predominantly stabilized by a robust bidentate coordination of guanidinium with a carboxylate group formed from the deprotonation of one side group of the crown ether. The released proton is transferred to the amino terminus of arginine, which then coordinates with the crown ether ring. In an alternative type of conformation, partly consistent with experiment, the amino terminus is neutral and the guanidinium group inserts into the crown ether cavity. In the +2 complexes, arginine is always doubly protonated and the most stable conformations are characterized by a tripodal coordination of the ammonium -NH3+ group of arginine with the oxygen atoms of the macrocycle ring, while the interactions of the amino acid with the side carboxylic acid groups of the crown ether acquire a remarkable lesser role.

Isolated complexes of the amino acid arginine with polyether and polyamine macrocycles, the role of proton transfer.

The distinct basicity of the guanidinium side-group of arginine (Arg) sustains specific interactions involved in essential biochemical processes. The sensing of arginine is therefore key in modern biotechnology and bioanalysis. In this context, the development of molecular receptors based on crown ether building blocks has demonstrated great potential. We investigate the complexes formed by arginine with two benchmark macrocycles, 12-crown-4 (1,4,7,10-tetraoxacyclododecane) and its N-substituted analog cyclen (1,4,7,10-tetraazacyclododecane). Isolated complexes with a net charge +1 are characterized with infrared action vibrational spectroscopy and quantum mechanical computations in order to determine the most stable coordination arrangements and to elucidate the location of the protons involved. Remarkably, although arginine retains a net positive charge in its complex with 12-crown-4, it becomes zwitterionic in the cyclen complex. In this latter case, the guanidinium group remains protonated while a proton transfer from the carboxylic group occurs, leading to a charged -NH2+ moiety in cyclen. Natural bond orbital analysis is employed to characterize the intermolecular H-bonds responsible for the stability of both complexes. Protonated arginine interacts with 12-crown-4 through the guanidinium side group, in a conformation that resembles the one expected for crown-Arg binding in peptidic chains. In contrast, the cyclen complex involves the coordination of the carboxylate anionic group with a N-H bond of the protonated amine group cyclen, and plausible but less relevant interactions with the guanidinium group.

Isolated alkali cation complexes of the antibiotic ionophore nonactin: correlation with crystalline structures.

The antibiotic activity of nonactin is sustained by its ability to transport K+ across lipophilic phases, e.g., the cell membranes. Such a feature can be traced back to a specific ionophoric behavior and to a balanced hydrophobicity modulated by the formation of a cation complex. In this study, the dominant conformations and coordination arrangements in the alkali cation complexes (Na+, K+, Cs+) of nonactin are characterized by means of action vibrational spectroscopy and quantum chemical computations. The low energy conformers of the complexes comprise compact inclusion structures, in which the cation interacts with a varying number of oxygen atoms of the carbonyl and oxolane ring groups of the nonactin macrocycle. The spectroscopy experiments indicate that the three alkali complexes explored are formed in a S4 conformation. This is in contrast with previous crystallography studies, which concluded that the symmetry of the most stable conformer of the complex changes qualitatively with the cation size, from C2 for Na+ to S4 for K+ and Cs+. Computations with different hybrid density functionals lead to contradictory predictions that appear to be quite sensitive to the modelling of the long range interactions in the coordination arrangements. The stabilization of the nonactin-Na+ complex in the C2 or S4 forms emerges as a subtle feature that may be tuned with an appropriate control of the environmental conditions, and constitutes a challenging benchmark to confront novel computational methods for supramolecular systems.

Benchmark Ditopic Binding of Cl- and Cs+ by the Macrocycle Hexacyclen.

The ditopic binding of organic and inorganic anions and cations constitutes a distinct feature of polyazamacrocycles that underlies their action as intermediate docking and exchange ionophoric sites for tailored supramolecular synthesis and sensors. This work investigates the Cl- and Cs+ complexes formed by hexacyclen (1,4,7,10,13,16-hexaazacyclooctadecane, ha18c6), a benchmark building block of ion-pair polyamine receptors. IR action spectroscopy is employed to characterize the anionic and cationic complexes under controlled environmental conditions in an ion trap. This allows for accurate modeling of the isolated complexes with quantum chemical computations. A comparison of the experimental and computational spectra serves to assess the low-energy conformers dominantly populated at room temperature, which comprise, in both cases, three structures of Cs , C2 , and C3v symmetry with relative energies within about 5 kJ mol-1 . The ion-pair complex Cl- -ha18c6-Cs+ is predicted to host the cation and anion on opposite sides of the macrocycle in a C3v conformation that does not correlate with the lowest energy structures of the binary complexes. This indicates that the formation of the ion-pair complex in its most stable conformation demands a rearrangement of the hexacyclen ring structure upon the incorporation of the counterion.