Through-space scalar spin-spin coupling: from rigid intramolecular cases to short-lived van der Waals complexes.

We will discuss, with the help of few selected examples, how the concept of through-space scalar spin-spin coupling between non covalently bonded nuclei has evolved in recent years. We will first present systems where 'no covalent bond' actually means that the two atoms are separated by a large number of bonds; then we will see cases where it is referred to true van der Waals dimers, but with the two atoms somehow constrained in their positions; we will finish with the most recent examples of liquids and even gaseous mixtures with full translational degrees of freedom in a regime of intermolecular/interatomic fast exchange.

Detailed investigation of the binding abilities of the heterodomain of a multiHis cyclopeptide toward Cu(II) ions.

Cyclopeptides hold significant relevance in various fields of science and medicine, due to their unique structural properties and diverse biological activities. Cyclic peptides, characterized by intrinsically higher conformational order, exhibit remarkable stability and resistance to proteolytic degradation, making them attractive candidates for developing targeted drug delivery systems. The aim of this work is to elucidate the unique coordination properties of the multi-His cyclic peptide with c(HDHKHPHHKHHP) sequence (HDCP - heterodomain cyclopeptide). This peptide, indeed, is able to form homo- and hetero-dinuclear complexes in a wide pH range, being thus a good chelator for Cu(II) ions. Herein, we present the results of a combined study, involving potentiometric, spectroscopic (UV-Vis, CD, and EPR), and computational investigations, on its coordination properties. To better understand the interaction pattern with Cu(II) metal ions, two other peptides, each one bearing only one of the two binding domains of HDCP are also considered in this study: c(HDHKHPGGKGGP) = CP1, c(GKGGKPHHKHHP) = CP2, which share sequence fragments of HDCP and allow separate investigations of its coordination domains.

Computational NMR spectroscopy of 205 Tl.

We have investigated the NMR chemical shift of 205 Tl in several thallium compounds, ranging from small covalent Tl(I) and Tl(III) molecules to supramolecular complexes with large organic ligands and some thallium halides. NMR calculations were run at the ZORA relativistic level, with and without spin-orbit coupling using few selected GGA and hybrid functionals, namely BP86, PBE, B3LYP, and PBE0. We also tested solvent effects both at the optimization level and at the NMR calculation step. At the ZORA-SO-PBE0 (COSMO) level of theory we find a very good performance of the computational protocol that allows to discard or retain possible structures/conformations based on the agreement between the calculated chemical shift and the experimental value.

Phase behaviour of mixtures of charged soft disks and spheres.

We have investigated the phase behaviour of mixtures of soft disks (Gay-Berne oblate ellipsoids, GB) and soft spheres (Lennard-Jones, LJ) with opposite charge as a model of ionic liquid crystals and colloidal suspensions. We have used constant volume Molecular Dynamics simulations and fixed the stoichiometry of the mixture in order to have electroneutrality; three systems have been selected GB : LJ = 1 : 2, GB : LJ = 1 : 1 and GB : LJ = 2 : 1. For each system we have selected three values of the scaled point charge q* of the GB particles, namely 0.5, 1.0 and 2.0 (and a corresponding negative scaled charge of the LJ particles that depends on the stoichiometric ratio). We have found a very rich mesomorphism with the formation, as a function of the scaled temperature, of the isotropic phase, the discotic nematic phase, the hexagonal columnar phase and crystal phases. While the structure of the high temperature phases was similar in all systems, the hexagonal columnar phases exhibited a highly variable morphology depending on the scaled charge and stoichiometry. On the one hand, GB : LJ = 1 : 2 systems form lamellar structures, akin to smectic phases, with an alternation of layers of disks (exhibiting an hexagonal columnar phase) and layers of LJ particles (in the isotropic phase). On the other hand, for the 2 : 1 stoichiometry we observe the formation of a frustrated hexagonal columnar phase with an alternating tilt direction of the molecular axis. We rationalize these findings based on the structure of the neutral ion pair dominating the behaviour at low temperature and high charge.

Phase coexistence in [C22/C1MIm]+[NO3]- ionic-liquid mixtures and first-order phase transitions from homogeneous liquid to smectic B by varying the cation ratio.

We perform molecular dynamics simulations to investigate the transition processes of [C22/C1MIm]+[NO3]- binary mixtures by varying the cation ratio of C22 to C1 at a fixed temperature of 400 K. The cation ratio is tuned by ranging C22 percentage from 0% to 100% with a fixed number of 4096 total simulated ion pairs. Our simulated-annealing results indicate that, at 400 K, pure C1 is a homogeneous liquid whilst pure C22 is an ionic liquid crystal (ILC) of smectic-B (SmB) type. With increasing C22 percentage, the system goes through a first-order phase transition from homogeneous liquid to nano-fragment liquid in the range from 15% to 17.5%, during which some of the individual cationic alkyl side chains locally aggregate to form small bundles "floating" in the polar "solvent" composed of anions and cationic head groups. Although the side chains in each bundle are parallelly aligned, the bundles distribute randomly without a global orientation. As the C22 percentage further increases, another first-order phase transition occurs to bring the system into the SmB ILC phase. Particularly, when the C22 percentage is in the range from 45% to 50%, the SmB phase coexists with the liquid phase containing both individual and bundled alkyl side chains.

Correction: The structuring effect of the alkyl domains on the polar network of ionic liquid mixtures: a molecular dynamics study.

Correction for 'The structuring effect of the alkyl domains on the polar network of ionic liquid mixtures: a molecular dynamics study' by Valerio Mazzilli et al., Phys. Chem. Chem. Phys., 2022, 24, 18783-18792, https://doi.org/10.1039/D2CP02786K.

The structuring effect of the alkyl domains on the polar network of ionic liquid mixtures: a molecular dynamics study.

By using molecular dynamics simulations, we investigate the structural and dynamic properties of mixtures of 1,3-dimethylimidazolium bis(trifluoromethanesulfonyl)imide, [C1C1im][Tf2N] and 1-dodecyl-3-methylimidazolium bis(trifluoromethanesulfonyl)imide, [C12C1im][Tf2N] (also C1 and C12 in short). Such mixtures feature an imidazolium bistriflimide salt with a very short alkyl chain, not giving rise to any nano-segregation as a pure component, with another one with a longer alkyl chain that exhibits a substantial nano-segregation as a pure liquid. As the mole fraction of the long-chain component C12 is increased, the so-called pre-peak of the structure factor S(q), occurring in the region 1-3 nm-1, shows a shift to higher values of the wavevector q, mirroring a decrease of the corresponding correlation length. Moreover, the intensity of the pre-peak strongly increases with the C12 concentration. These results are in very good agreement with experimental X-ray scattering data in the literature. On the other hand, the diffusion of the ions is found to exhibit a simple behaviour consistent with the increased viscosity of the mixture, and these results are also in good agreement with NMR experimental data from the literature. The simulation results are rationalized as caused by a structuring effect, similar to the hydrophobic effect, of the alkyl domains of the C12 component dissolved in the "solvent" represented by the C1 cation, the Tf2N- anion and the C12 cation head. In short, the exclusion of the alkyl chains from the polar network, a process mostly governed by electrostatic interactions, favours the formation of hydrophobic domains, which in turn exert a structuring effect on the ions of the polar domains, favouring a stronger ionic interaction. This is finally reflected in a shorter correlation length and a higher intensity of the pre-peak of the structure factor S(q) as the C12 mole fraction is increased. At variance with the microscopic structure, the diffusion of all three types of ions is not strongly influenced by the nano-segregation and is essentially dependent on the viscosity of the mixture.

Activation of Vegetable Oils by Reaction with Maleic Anhydride as a Renewable Source in Chemical Processes: New Experimental and Computational NMR Evidence.

Vegetable oils are bio-based and sustainable starting materials that can be used to develop chemicals for industrial processes. In this study, the functionalization of three vegetable oils (grape, hemp, and linseed) with maleic anhydride was carried out either by conventional heating or microwave activation to obtain products that, after further reactions, can enhance the water dispersion of oils for industrial applications. To identify the most abundant derivatives formed, trans-3-octene, methyl oleate, and ethyl linoleate were reacted as reference systems. A detailed NMR study, supported by computational evidence, allowed for the identification of the species formed in the reaction of trans-3-octene with maleic anhydride. The signals in the 1H NMR spectra of the alkenyl succinic anhydride (ASA) moieties bound to the organic chains were clearly identified. The reactions achieved by conventional heating were carried out for 5 h at 200 °C, resulting in similar or lower amounts of ASA units/g of oil with respect to the reactions performed by microwave activation, which, however, induced a higher viscosity of the samples.

Xenon Diffusion in Ionic Liquids with Blurred Nanodomain Separation.

The dynamics of xenon gas, loaded in a series of 1-alkyl-3-methylimidazolium based ionic liquids, probes the formation of increasingly blurred polar/apolar nanodomains as a function of the anion type and the cation chain length. Exploiting 129 Xe NMR spectroscopy techniques, like Pulse Gradient Spin Echo (PGSE) and inversion recovery (IR), the diffusion motion and relaxation times are determined for 1-alkyl-3-methylimidazolium bis(trifluoromethylsulfonyl)imide [Cn C1 im][TFSI]. A correlation between the ILs nano-structure and both xenon diffusivity and relaxation times, as well as chemical shifts, is outlined. Interestingly, comparison with previous results of the same properties in the homologous imidazolium chlorides and hexafluorophospate shows an opposite trend with the alkyl chain length. Classical molecular dynamics (MD) simulations are used to calculate the xenon and cation and anion diffusion coefficients in the same systems, including imidazolium cations with longer chains (n=4, 6, 8 … 20). An almost quantitative agreement with the experiments validates the MD simulations and, at the same time, provides the necessary structural and dynamic microscopic insights on the nano-segregation and diffusion of xenon in bistriflimide, chloride and hexafluorphosphate salts allowing to observe and rationalize the shaping effect of the cation in the nanostructure.

The effect of hydration on the stability of ionic liquid crystals: MD simulations of [C14C1im]Cl and [C14C1im]Cl·H2O.

The thermal range of the stability of Ionic Liquid Crystal (ILC) phases of imidazolium ILCs, and the type of the mesophase itself are affected by several molecular structural features, the two prominent ones being the alkyl chain length and the counter-anion. Hydration is also very important: monohydrate samples of 1-alkyl-3-methylimidazolium halides have a higher clearing point and a wider thermal range of the stability of the ionic smectic phase, compared with the analogous anhydrous sample. To understand the reasons, at a microscopic level, for such increased stability due to hydration, we run classical Molecular Dynamics (MD) simulations of a typical ionic liquid crystal, 1-tetradecyl-3-methylimidazolium chloride, and of its monohydrate form. We tested a full-charge non-polarizable force field and a scaled-charge version having the total charge of the ions scaled by a factor of 0.80. Comparison of the structural and dynamic properties with available experimental data reveals that the scaling of the charge by a factor of 0.80 results in a good agreement between simulated and experimental data and it sheds light on the microscopic mechanism responsible for the increased stability of the monohydrated phase. A hydrogen-bond network between water and the chloride anion is established in the ionic layer which increases the stability of the ionic layer; this in turn increases the nano-segregation between the ionic and hydrophobic layers which eventually produce an increased order of the alkylic layer as well.

Influence of the ion size on the stability of the smectic phase of ionic liquid crystals.

The thermotropic phase behavior of ionic liquids and ionic liquid crystals based on novel N-alkyl-3-methylpyridinium halides, trihalides and dichloroiodates was experimentally studied by polarized optical spectroscopy (POM) and differential scanning calorimetry (DSC) as well as by molecular dynamics (MD) simulation. In the experiments, the existence and thermal range of stability of the smectic phase of these ionic liquid crystals are found to strongly depend on the volume ratio between the cation and anion, that is their relative size. Only compounds with a relatively large volume ratio of the cation to anion, i.e., those with longer cationic alkyl chains and monoatomic halide anions, have a stable smectic A phase. Both melting points and clearing points increase with such a ratio. The MD simulation results qualitatively agree very well with the experimental data and provide molecular details which can explain the experimentally observed phenomena: the stronger van der Waals interactions from the longer alkyl chains and the stronger electrostatic interactions from the smaller anions with a higher charge density increase the stability of both the crystal phase and the smectic phase; this also prevents the ionic layers from easily mixing with the hydrophobic regions, a mechanism that ultimately leads to a nanosegregated isotropic liquid phase.

One-bond 1 J(15 N─19 F) spin-spin coupling constants of cationic fluorinating reagents: Insights from DFT calculations.

We have investigated, by means of density functional theory protocols, the one-bond 1 J(15 N─19 F) spin-spin coupling constants in a series of fluorinating reagents, containing the N─F bond, recently studied experimentally. The results of the calculations show a very good linear relationship with the experimental values, even though only the M06-2X(PCM)/pcJ-2//B3LYP/6-311G(d,p) level affords a very low mean absolute error. The calculations allow to analyze the various molecular orbitals contributions to the J coupling and to rationalize the observed positive sign, corresponding to a negative sign of the reduced spin-pin coupling constant K(N─F). Moreover, of the four Ramsey contributions, only the diamagnetic spin orbit is negligible, whereas the paramagnetic spin orbit and spin dipole terms decrease the magnitude of the Fermi contact (FC) term by an amount that goes from a minimum of 35% up to more than 60% of the FC term itself. Several effects have been investigated, namely, the contribution of the long-range solvent reaction field, relativistic corrections, and conformational and vibrational effects.

Computational NMR Spectroscopy of Ionic Liquids: [C4C1im]Cl/Water Mixtures.

In this work, I have analyzed the structure of binary mixtures of 1-butyl-3-methylimidazolium chloride ionic liquid, [C4C1im]Cl, and water, using computational NMR spectroscopy. The structure of the complex fluid phase, where the ionic and hydrophobic nature of ionic liquids is further complicated by the addition of water, is first generated by classical Molecular Dynamics (MD) and then validated by calculating the NMR properties with DFT at the ONIOM(B3LYP/cc-pVTZ//B3LYP/3-21G) on clusters extracted during the MD trajectories. Three ionic liquid/water mixtures have been considered with the [C4C1im]Cl mole fraction of 1.00, 0.50, and 0.01, that is the pure ionic liquid [C4C1im]Cl, the equimolar [C4C1im]Cl/water mixture, and a diluted solution of [C4C1im]Cl in water. A good agreement is obtained with published experimental data that, at the same time, validates the structural features obtained from the MD and the force field used, and provides an example of the power of NMR spectroscopy applied to complex fluid phases.

"Through-Space" Relativistic Effects on NMR Chemical Shifts of Pyridinium Halide Ionic Liquids.

We have investigated, using two-component relativistic density functional theory (DFT) at ZORA-SO-BP86 and ZORA-SO-PBE0 level, the occurrence of relativistic effects on the 1 H, 13 C, and 15 N NMR chemical shifts of 1-methylpyridinium halides [MP][X] and 1-butyl-3-methylpyridinium trihalides [BMP][X3 ] ionic liquids (ILs) (X=Cl, Br, I) as a result of a non-covalent interaction with the heavy anions. Our results indicate a sizeable deshielding effect in ion pairs when the anion is I- and I3- . A smaller, though nonzero, effect is observed also with bromine while chlorine based anions do not produce an appreciable relativistic shift. The chemical shift of the carbon atoms of the aromatic ring shows an inverse halogen dependence that has been rationalized based on the little C-2s orbital contribution to the σ-type interaction between the cation and anion. This is the first detailed account and systematic theoretical investigation of a relativistic heavy atom effect on the NMR chemical shifts of light atoms in the absence of covalent bonds. Our work paves the way and suggests the direction for an experimental investigation of such elusive signatures of ion pairing in ILs.

A combined LX-NMR and molecular dynamics investigation of the bulk and local structure of ionic liquid crystals.

The unique power of NMR spectroscopy in anisotropic media (LX-NMR) as a tool to obtain local and bulk structural information, combined with the effectiveness of molecular dynamics simulations at the atomistic level, shows very attractive potentialities for the study of interesting, even though still poorly understood, materials such as Ionic Liquid Crystals (ILCs). In this work, we focused our attention, in particular, on the orientational ordering of two mesophases: 1-dodecyl-3-methylimidazolium chloride, [C12C1im]Cl, and 1-dodecyl-3-methylimidazolium tetrafluoroborate, [C12C1im][BF4]. Both ILCs were studied by a 2H NMR direct investigation of the molecules forming the phases, suitably deuterated, and by 1H NMR spectroscopy, using the small rigid probe-solutes 1,4-dichlorobenzene (DCB), dissolved in [C12C1im][BF4] and [C12C1im]Cl, and 1,4-dibromobenzene (DBB) dissolved in [C12C1im][BF4], to probe the local, internal structure and organization of the mesophases. The experimental results were then compared with the predictions, by atomistic MD simulations, of the structure of the smectic phase of the two salts, at two selected temperatures, containing a single DCB molecule as a probe. The MD simulations show that the DCB solute is distributed only within the hydrophobic layers of the ILC. Orientational order parameters of the imidazolium cations and of the DCB molecule were obtained and compared with the experiments, showing a general good agreement and allowing a deeper understanding of the microscopic structure of the systems.

A coarse-grained model of ionic liquid crystals: the effect of stoichiometry on the stability of the ionic nematic phase.

We have investigated, by means of molecular dynamics simulations, the phase behaviour of mixtures of charged ellipsoidal Gay-Berne (GB) particles and spherical Lennard-Jones (LJ) particles, as a coarse-grained model of ionic liquid crystals (ILCs). The anisotropic GB particles represent cations usually found in ILCs, for example, pyridinium or bipyridinium salts, while the spherical LJ particles are taken as a model of anions like common halides, hexafluorophosphate and tetrafluoroborate. Here we have focused our attention on the effect of the stoichiometry of the system (that is, the GB : LJ ratio n : m in the salt formula [GB]n[LJ]m) on the stability and thermal range of the ionic liquid crystal phases formed, with special attention to the ionic nematic phase. To isolate the stoichiometry effect, a comparison of four different systems with GB : LJ ratios of 1 : 3, 1 : 2, 1 : 1 and 2 : 1 is made by keeping the packing fraction and the charge of the minor component fixed. Our results suggest a way to improve the stability of the ionic nematic phase by enhancing the anisotropic van der Waals interaction compared to the Coulomb interaction, and by increasing the proportion of anisotropic particles in the mixture.

The 125Te Chemical Shift of Diphenyl Ditelluride: Chasing Conformers over a Flat Energy Surface.

The interest in diphenyl ditelluride (Ph2Te2) is related to its strict analogy to diphenyl diselenide (Ph2Se2), whose capacity to reduce organic peroxides is largely exploited in catalysis and green chemistry. Since the latter is also a promising candidate as an antioxidant drug and mimic of the ubiquitous enzyme glutathione peroxidase (GPx), the use of organotellurides in medicinal chemistry is gaining importance, despite the fact that tellurium has no recognized biological role and its toxicity must be cautiously pondered. Both Ph2Se2 and Ph2Te2 exhibit significant conformational freedom due to the softness of the inter-chalcogen and carbon⁻chalcogen bonds, preventing the existence of a unique structure in solution. Therefore, the accurate calculation of the NMR chemical shifts of these flexible molecules is not trivial. In this study, a detailed structural analysis of Ph2Te2 is carried out using a computational approach combining classical molecular dynamics and relativistic density functional theory methods. The goal is to establish how structural changes affect the electronic structure of diphenyl ditelluride, particularly the 125Te chemical shift.

Aggregation behavior of dihexadecylviologen bistriflimide ionic liquid crystal in different solvents: influence of polarity and concentration.

Solutions of 1,1'-dihexadecyl-4,4'-bipyridinium di[bis(trifluoromethanesulfonyl)imide] salt, also known as dihexadecylviologen bistriflimide, in deuterated acetonitrile (ACN), dichloromethane (DCM) and chloroform (CDCl3), respectively, were investigated by the combination of 1H and DOSY NMR spectroscopy, DFT calculations and MD simulation to understand the influence of solvent polarity and solute concentration (10-5-10-1 M) on its aggregation behavior. We found that the polar solvent acetonitrile (ACN) does not favor ion aggregation and cluster formation. In the whole range of concentrations investigated, the system appears to be dominated by neutral ion pairs composed of one cation and two anions, possibly in fast equilibrium (on the NMR time scale) with small or slightly larger aggregates. The diffusion coefficient of the cationic species is only weakly affected by concentration. In contrast, the low-polar solvents of chloroform (CDCl3) and dichloromethane (DCM) strongly favor cluster formation above a certain concentration and the viologen diffusion coefficient in CDCl3 is much smaller and more strongly dependent on concentration than that in ACN. The information obtained from the MD simulations suggests that the aggregates have a structure similar to the isotropic liquid phase of the viologen-based ionic liquids and ionic liquid crystals. The lifetimes of such large clusters appear to be relatively long, beyond the time scale of tens of nanoseconds. Moreover, the results from the aromatic proton NMR resonances provide some insights on the dielectric constants inside the viologen aggregates.

Ion pairing in 1-butyl-3-methylpyridinium halide ionic liquids studied using NMR and DFT calculations.

We present the 1H, 13C and 15N NMR chemical shifts of bulk ionic liquids based on 1-butyl-3-methylimidazolium (the cation also known as 1-butyl-3-picolinium) halides (Cl-, Br- and I-) and tribromide (Br3-) salts. A characterization in solution of the analogous ICl2- and I3- salts is also reported. A series of DFT calculations has been run to predict the features of the NMR spectra of the pure ILs based on a few selected supramolecular ionic aggregates. To test the effect of temperature, and vibrational and conformational motions, only for the chloride salt, we also run first-principles molecular dynamics simulations of the ion pair in the gas phase, using the ADMP scheme (Atom Centered Density Matrix Propagation molecular dynamics model). The aim of our investigation is to test whether a simple DFT based approach of ion-pairing in ionic liquids is capable of providing reliable results and under which conditions the protocol is robust. We obtained a very good agreement between the calculated and experimental spectra for the three halides, where the bulk structure of the ILs is dominated by H-bond interactions between the X- anion (X = Cl, Br and I) and the ortho protons of the pyridinium ring (a structural arrangement not too different from the solid-state structure of pyridinium halides). In contrast, when the H-bond is weak, as in the Br3- case, a number of supramolecular arrangements exist in solution and the simple DFT calculations of a few selected cases cannot exhaustively explore the complete energy landscape. Moreover, the dynamic effects due to thermal motion, evaluated by ADMP MD simulations of the chloride salt, appear to be not very significant.

New Sulfur-Containing Polyarsenicals from the New Caledonian Sponge Echinochalina bargibanti.

Arsenicin A (C3H6As4O3) was isolated from the New Caledonian poecilosclerid sponge Echinochalina bargibanti, and described as the first natural organic polyarsenic compound. Further bioguided fractionation of the extracts of this sponge led us to isolate the first sulfur-containing organic polyarsenicals ever found in Nature. These metabolites, called arsenicin B and arsenicin C, are built on a noradamantane-type framework that is characterized by an unusual As⁻As bonding. Extensive NMR measurements, in combination with mass spectra, enabled the assignment of the structure for arsenicin B (C3H6As4S2) as 2. The scarcity of arsenicin C and its intrinsic chemical instability only allowed the collection of partial spectral data, which prevented the full structural definition. After the extensive computational testing of several putative structures, structure 3 was inferred for arsenicin C (C3H6As4OS) by comparing the experimental and density functional theory (DFT)-calculated ¹H and 13C NMR spectra. Finally, the absolute configurations of 2 and 3 were determined with a combined use of experimental and time-dependent (TD)-DFT calculated electronic circular dichroism (ECD) spectra and observed specific rotations. These findings pose great challenges for the investigation of the biosynthesis of these metabolites and the cycle of arsenic in Nature. Arsenicins B and C showed strong antimicrobial activities, especially against S. aureus, which is comparable to the reference compound gentamycin.