Structural flexibility of favipiravir and its structural analogues in solutions: experimental and computational insight.

Combined UV-vis and quantum chemical studies of the structural flexibility and tautomerism of 6-R-3-hydroxy-2-pyrazine carboxamides in solutions revealed that their keto-enol transformations are accompanied by the deprotonation of enol tautomers and the formation of the corresponding anionic species. Both the solvent and the 6-R substituent strongly influence the relative abundance of the above forms in solutions. Anions are not formed in 1,2-dichloroethane (DCE), but the probability of deprotonation in neutral water and N,N-dimethylformamide (DMF) increases in the order R = H < F < NO2. Only enol tautomers of all solutes are found in DCE. DMF stabilizes keto forms only moderately and assists much strongly in the deprotonation of all three compounds. Water tends to stabilize both keto tautomers and deprotonated anions: the keto form dominates in the case of R = H (antiviral drug T-1105), the anions are found exclusively for R = NO2, and the aqueous solution of another antiviral drug, favipiravir (R = F), contains both the keto tautomer and the anionic form. The results of quantum chemical free energy calculations are in agreement with the experimental observations.

Computational analysis of the vibrational spectra and structure of aqueous cytosine.

The recently developed efficient protocol for the explicit quantum mechanical modeling of the structure and IR spectra of liquids and solutions [Katsyuba et al., J. Phys. Chem. B, 2020, 124, 6664-6670] is used to describe aqueous solutions of cytosine. The same cluster model of a solute surrounded by the first solvation shell of solvent molecules was shown to be sufficient to reproduce experimental vibrational frequencies and relative IR and Raman intensities. An equally good quality of Raman spectra was provided by B3LYP-D3/def2-TZVP and B3LYP-D3/aug-cc-pVDZ simulations. Computations using the PBE functional were sufficient for modeling of the IR spectra but failed in the simulations of Raman scattering. It is shown that strong changes of frequencies and relative intensities of Raman and IR bands of cytosine, caused by its hydration, cannot be completely assigned to the influence of hydrogen bonds (HBs) with 7 or 8 closest water molecules. They are rather ascribed to the combined effect of solute-solute and solute-solvent HBs with the participation of at least 30 water molecules separating cytosine from the bulk solvent. This suggests that the vibrational modes and derivatives of the polarizability and dipole moment of the solute are mainly locally influenced by its first hydration shell, while the influence of bulk water is rather modest.

Computer-aided simulation of infrared spectra of ethanol conformations in gas, liquid and in CCl4 solution.

The recently developed efficient protocol combining implicit and explicit, accurate quantum-mechanical modeling of the condensed state (Katsyuba et al., J. Chem. Phys. 155, 024507 [2021]) is used to describe the IR spectra of liquid ethanol and its solutions in CCl4 . The relative abundance of the anti and gauche conformers of ethanol is shown to increase from ~40:60 in the gas phase to ~55:45 in the liquid phase. In spite of a moderate impact of media effects on the conformational composition of the liquid, the solvent strongly influences vibrational frequencies, IR intensities, and normal modes of each conformer, producing qualitatively different spectra compared to the gas phase and CCl4 solution. Further, these solvent effects affecting IR frequencies and intensities depend not only on the conformation of the solvated molecule but also on the solvating species. Nevertheless, vibrational frequencies of anti and gauche conformers of liquid ethanol and its several isotopomers practically coincide with each other. Convenient liquid-state conformational markers in the fingerprint region of IR spectra are revealed for the hydroxyl-deuterated species: CH3 CH2 OD, CH3 CHDOD, CH3 CD2 OD, and CD3 CD2 OD.

Deep-Blue Emissive Copper(I) Complexes Based on P-Thiophenylethyl-Substituted Cyclic Bisphosphines Displaying Photoinduced Structural Transformations of the Excited States.

A synthetic method for a primary 2-(thiophen-2'-yl)ethylphosphine was developed. The reaction of thiophenylethylphosphine with paraformaldehyde and primary arylamines leads to the formation of cyclic bisphosphines, namely, 1,5-di(aryl)-3,7-bis(thiophenylethyl)-1,5-diaza-3,7-diphosphacyclooctane (aryl = phenyl, p-tolyl). The obtained bisphosphines form cationic bis-P,P-chelate complexes with copper(I) tetrafluoroborate, which were structurally characterized by NMR spectroscopy, mass spectrometry, and elemental and XRD analyses. Surprisingly, the copper(I) complexes display a multiband emission in the solid state with maxima at 355-360, 425-430, and 480-490 nm and nanosecond lifetimes (1.2-1.4 ns) upon a 335 nm excitation. The excitation of the complexes at 360 nm at room temperature results in a deep-blue emission at 425-430 nm and a tail at 460-490 nm. A temperature decrease leads to an increased intensity of the emission band at 480 nm, while the luminescence lifetimes insignificantly increased up to 14 ns. Quantum chemical calculations explain the observed unusual luminescent behavior by the existence of "undistorted" and "flattened" singlet excited states of copper(I) complexes at room temperature and at 77 K, respectively.

What quantum chemical simulations tell us about the infrared spectra, structure and interionic interactions of a bulk ionic liquid.

The recently developed efficient protocol to explicit quantum mechanical modeling of the structure and IR spectra of liquids and solutions [Katsyuba et al., J. Phys. Chem. B, 2020, 124, 6664-6670] is applied to ionic liquid 1-ethyl-3-methyl-imidazolium tetrafluoroborate [Emim][BF4], and its C2-deuterated analog [Emim-d][BF4]. It is shown that the solvation strongly modifies the frequencies and IR intensities of both cationic and anionic components of the ionic liquids. The main features of the bulk spectra are reproduced by the simulations for cluster ([Emim][BF4])8, representing an ion pair solvated by the first solvation shell. The geometry of the cluster closely resembles the solid-state structure of the actual ionic liquid and is characterized by short contacts of all CH moieties of the imidazolium ring with [BF4]- anions. Both structural and spectroscopic analyses allow the contacts to be interpreted as hydrogen bonds of approximately equal strength. The enthalpies of these liquid-state H-bonds, estimated with the use of empirical correlations, amount to 1.2-1.5 kcal mol-1, while the analogous estimates obtained for the gas-phase charged species [Emim][BF4]2- and [Emim]2[BF4]+ increase to 3.6-3.9 kcal mol-1.

Thermodynamics of trans/gauche conformational equilibria and vibrational spectra of 1,2-dihaloethanes in various media.

The recently developed efficient protocols to implicit [Grimme et al., J. Phys. Chem. A 125, 4039-4054 (2021)] and explicit quantum mechanical modeling of non-rigid molecules in solution [Katsyuba et al., J. Phys. Chem. B 124, 6664-6670 (2020)] are used to describe conformational equilibria of 1,2-dichloroethane and 1,2-dibromoethane in various media. Two approaches for evaluation of trans/gauche free energy differences, ΔGt-g, are compared: (a) direct ΔGt-g computation in implicit solution; (b) the use, together with experimental intensities, of infrared absorption coefficients and Raman scattering cross sections computed for each explicitly modeled solution. The same cluster model of a solute surrounded by the first solvation shell of solvent molecules was used to simulate both Raman and IR spectra. The good agreement between the two approaches indicates the reliability of both methods. The importance of using correct absorption coefficients and Raman scattering factors for each medium is discussed. The ΔGt-g estimates from both implicit and explicit solvation simulations were combined with experimentally measured enthalpy differences ΔHt-g available in the literature to obtain condensed-state ΔSt-g estimates.

Revisiting conformations of methyl lactate in water and methanol.

The recently developed efficient protocols to implicit [Grimme et al., J. Phys. Chem. A 125, 4039-4054 (2021)] and explicit quantum mechanical modeling of non-rigid molecules in solution [Katsyuba et al., J. Phys. Chem. B 124, 6664-6670 (2020)] are applied to methyl lactate (ML). Building upon this work, a new combination scheme is proposed to incorporate solvation effects for the computation of infrared (IR) absorption spectra. Herein, Boltzmann populations calculated for implicitly solvated single conformers are used to weight the IR spectra of explicitly solvated clusters with a size of typically ten solvent molecules, i.e., accounting for the first solvation shell. It is found that in water and methanol, the most abundant conformers of ML are structurally modified relative to the gas phase, where the major form is ML1, in which the syn conformation of the -OH moiety is stabilized by a OH⋯O=C intramolecular hydrogen bond (HB). In solution, this syn conformation transforms to the gauche form because the intramolecular HB is disrupted by explicit water molecules that form intermolecular HBs with the hydroxyl and carbonyl groups. Similar changes induced by the gas-solution transition are observed for the minor conformers, ML2 and/or ML3, characterized by OH⋯OCH3 intramolecular HB in the gas phase. The relative abundance of ML1 is shown to decrease from ∼96% in gas to ∼51% in water and ∼92% in methanol. The solvent strongly influences frequencies, IR intensities, and normal modes, resulting in qualitatively different spectra compared to the gas phase. Some liquid-state conformational markers in the fingerprint region of IR spectra are revealed.

Characterization of Conjugation Effects in the Series of Quinoxaline-2-ones by Means of Vibrational Raman Spectroscopy.

A broad series of quinoxalinone-based π-conjugated donor-acceptor fluoro- and NLO-phores is characterized by means of Raman spectroscopy and single-crystal X-ray analysis supported by quantum chemical computations. Intense Raman spectroscopic markers that allow the differentiation of even closely related structures are identified. The intensities of these bands are shown to be related to the conjugation of the different molecular moieties, and they can provide an estimation of its extent. The intensity redistribution between these markers serves as a source of auxiliary structural information capable of pointing to a distortion of the conjugation or to the influence of aggregation effects in the condensed state. A simple relation between the intensity of the marker and the position and oscillator strength of the lowest-energy electronic absorption band of quinoxalinones allows a linking of the Raman effect with the optical properties of these compounds, which can be used for the rational design of novel species with improved optical characteristics.

The Assembly of Unique Hexanuclear Copper(I) Complexes with Effective White Luminescence.

The unique L2Cu6I6 complexes containing two Cu3I3 units have been obtained via reaction of 1,5-diaza-3,7-diphosphacyclooctanes bearing ethylpyridyl substituents at phosphorus atoms with an excess of copper iodide. The structure of one of the complexes was confirmed by X-ray diffraction. It was shown that the complexes can exist in two crystalline phases with different parameters of the unit cell, which were detected by the PXRD data analyses. The solvent-free crystalline phases of the complexes display rare solid-state white emission at room temperature, which is observed due to the presence of two broad bands in the emission spectra with maxima at 464 and 610 nm. Quantum chemical computations show that the high-energy band has 3(M+X)LCT origin, whereas the low-energy band is interpreted as 3CC. The quantum yields of white luminescence of complexes reach 15-20%.

Intriguing Near-Infrared Solid-State Luminescence of Binuclear Silver(I) Complexes Based on Pyridylphospholane Scaffolds.

A series of novel charged disilver(I) complexes with pyridyl-containing phospholanes was synthesized. These complexes were characterized using a range of spectroscopic techniques and single-crystal and powder X-ray diffraction. The complexes demonstrate solid-state near-infrared (NIR) luminescence (765-902 nm) that is unique for dinuclear AgI complexes. Combined spectroscopic/quantum chemical analysis suggests that the NIR luminescence of complexes 4-6 in the solid state is mainly due to crystal packing effects.

Fast Quantum Chemical Simulations of Infrared Spectra of Organic Compounds with the B97-3c Composite Method.

The ability of the quantum chemical computations to reproduce spectral positions and relative intensities of infrared (IR) bands for experimental vibrational spectra of organic molecules is assessed. The efficient B97-3c density functional approximation, routinely applicable to hundreds of atoms on a single processor, has been applied for the simulation of IR spectra for species containing up to 216 atoms. The results demonstrate that B97-3c, being much faster than the well-recognized hybrid functional B3LYP, offers similarly good quantitative performance in comparison to experimental data for relative IR intensities and fundamental frequencies (ν ≤ 2200 cm-1) for isolated molecules comprising from 3 to 21 first- or second-row atoms.

Benzimidazolylquinoxalines: novel fluorophores with tuneable sensitivity to solvent effects.

We report on the photophysical properties, conjugation, conformational behavior, intra- and intermolecular hydrogen bonds (HBs) of a series of novel fluorophores, consisting of 3-arylquinoxaline and benzimidazole moieties linked by a single CC bond. Computations employing density functional theory (DFT) reveal that conjugation between these moieties stabilizes syn-conformers with two HB centers located on the same side of the molecule. Anti-conformers form stronger intermolecular HBs with DMSO and DMF than syn-conformers, and this influences the energy gap between syn- and anti-forms, especially upon excitation of the molecules to the S1 state. Substituents introduced in various positions of the molecules modify their conformational behavior, and mutual disposition of excited singlet states relative to the ground states. Various substitution patterns produce very different effects on relative quantum yield of luminescence: from a moderate increase in polar DMSO and DMF relative to 1,2-dichloroethane solutions to complete quenching of emission which is observable in polar media. The observed behavior is understood with the aid of DFT and time-dependent DFT calculations. The tuneability of the spectroscopic range of the luminescence and especially of its sensitivity to environmental effects allows rational design of the novel fluorophores of this family for various applications.

A Rhodium Nanoparticle-Lewis Acidic Ionic Liquid Catalyst for the Chemoselective Reduction of Heteroarenes.

We describe a catalytic system composed of rhodium nanoparticles immobilized in a Lewis acidic ionic liquid. The combined system catalyzes the hydrogenation of quinolines, pyridines, benzofurans, and furan to access the corresponding heterocycles, important molecules present in fine chemicals, agrochemicals, and pharmaceuticals. The catalyst is highly selective, acting only on the heteroaromatic ring, and not interfering with other reducible functional groups.

Solvation and stabilization of palladium nanoparticles in phosphonium-based ionic liquids: a combined infrared spectroscopic and density functional theory study.

Analysis of infrared spectra of palladium nanoparticles (NPs) immersed in the tri-tert-butyl-R-phosphonium-based ionic liquids (ILs) demonstrates that both cations and anions of the ILs interact with the NPs. According to quantum-chemical simulations of these interactions, the binding energy of anions to the Pd6 cluster, taken as a minimal-size model of the NPs, increases from ∼6 to ∼27 kcal mol(-1) in the order [PF6](-)≈ [BF4](-) < [Tf2N](-) < [OTf](-) < [Br](-)≪ [TFA](-). In contrast, the binding energy for all types of the [Bu(t)3PR](+) cations slightly varies at about ∼22 kcal mol(-1) only moderately depending on the choice of the R moiety (n-pentyl, 2-hydroxyethyl, 2-methoxyethyl, 2-ethoxy-2-oxoethyl). As a result, the energies of interaction between a Pd6 cluster and various ion pairs, formed by the abovementioned counter-ions, follow the order found for the anions and vary from ∼24 to ∼47 kcal mol(-1). These values are smaller than the energy of addition of a Pd atom to a Pdn cluster (∼58 kcal mol(-1)), which suggests kinetic stabilization of the NPs in phosphonium-based ILs rather than thermodynamic stabilization. The results are qualitatively similar to the trends found earlier for interactions between palladium clusters and components of imidazolium-based ILs, in spite of much larger contributions of the London dispersion forces to the binding of the [Bu(t)3PR](+) cations to the cluster (up to 80%) relative to the case of 1-R-3-methylimidazolium cations (up to 40%).

Conjugation in and optical properties of 1-R-1,2-diphospholes and 1-R-phospholes.

The strength of conjugation between the diene moieties of 1-R-1,2-diphospholes and 1-R-phospholes and exocyclic phenyl groups of these P-heteroles has been quantitatively characterized by the use of Raman activities of the bands of the phenyl substituents. It is shown that conjugation in both types of phospholes is very similar to the conjugation of phenyl groups with the diene system of cyclopentadiene. Introduction of substituents (-OMe, -C(═O)H, -NO2, -NMe2, and -CH═CH2) in the para-position of the phenyl groups of 1-R-1,2-diphospholes extends π-delocalization of exocyclic groups into the electronic system of the 1,2-diphosphole ring, producing bathochromic shifts of the absorption bands up to 63 nm. In contrast, hypsochromic shifts up to 40 nm can be achieved by introduction of SnMe3 or SiMe3 groups at the phosphorus(III) atom of the 1,2-diphosphole and concomitant increase of aromaticity of the P-heterole. Conjugation shifts the "centre of gravity" of the whole electronic absorption spectrum, whereas positions of separate absorption bands are not simply dependent on conjugation lengths.

Computationally assisted vibrational spectroscopy of nucleic acid bases. 2. Thymine.

As in the case of cytosine [Phys. Chem. Chem. Phys. 2023, 25, 24121-24128], Raman and infrared (IR) spectra of aqueous thymine and its N-deuterated derivative, thymine-d2 have been computationally reproduced and interpreted with the use of the recently developed efficient protocol to explicit quantum mechanical modeling of structure and IR spectra of liquids and solutions [J. Phys. Chem. B, 2020, 124, 6664-6670]. A cluster model of a solute surrounded by 30 water molecules is shown to be sufficient to reproduce experimental vibrational frequencies and relative Raman intensities with the use of B3LYP-D3/def2-TZVP or B3LYP-D3/aug-cc-pVDZ simulations. Analogous PBE-D3 computations provided a less good, but still reasonably accurate, modeling of Raman spectra. It is shown that strong changes of frequencies and relative intensities of the Raman bands of thymine, caused by its hydration, can be interpreted mainly as a result of hydrogen bonding with 6 nearest water molecules. Non-negligible improvement of the quality of simulations for larger clusters comprising water molecules that do not have direct contacts with the solute, suggests that spectroscopic effects of hydration should be ascribed to the joined action of solute-solvent and solvent-solvent interactions. Nevertheless, the moderate number of water molecules required for successful simulations of the Raman spectra of aqueous thymine, suggests that the vibrational modes and derivatives of the polarizability of the solute are mainly locally influenced, while the effect of bulk water is rather modest.

Is there a simple way to reliable simulations of infrared spectra of organic compounds?

To assess the ability of the quantum-chemical computations to reproduce the experimental relative intensities in the infrared (IR) spectra of both the gas- and condensed-phase systems, the hybrid DFT functional B3LYP has been applied to simulation of IR spectra for species containing from three to twelve first- or second-row atoms, both in the gas phase and in CCl4 solutions. The results demonstrate that B3LYP, combined with the highly compact double-ζ basis set 6-31+G* and "scaled quantum mechanics" techniques, offers excellent quantitative performance in the calculations of relative IR intensities and frequencies (ν ≤ 2200 cm(-1)) for the bands of vibrations of medium-size isolated molecules, whereas it produces unsatisfactory results for the solutions of the same species. Neither larger basis sets nor implicit treatment of the media effects improve the agreement of the simulated spectra with the condensed-phase experiment. At the same time, some preliminary results suggest that explicit modeling of media effects could offer better quality of the IR spectral simulations for the condensed-phase systems.

Application of time-dependent density functional theory and optical spectroscopy toward the rational design of novel 3,4,5-triaryl-1-R-1,2-diphospholes.

Twenty 3,4,5-triaryl-1-R-1,2-diphospholes were studied within the framework of density functional theory (DFT) and experimentally by UV/vis spectroscopy to check their suitability for opto-electronic applications. Time-dependent DFT (TD-DFT) calculations employing the PBE0 hybrid density functional combined with moderately sized def-TZVP basis set were shown to excellently reproduce the experimental absorption spectra of various 1,2-diphospholes. Frontier molecular orbital analysis reveals that HOMO and LUMO are mainly localized on the diphosphole ring and, to some extent, on the aryl moieties. The HOMO-LUMO energy gap can be easily tuned by variation of substituents introduced in para-positions of the aryl moieties and, to a lesser extent, by modification of the R group at phosphorus atom. As a result, both position and intensity of the absorption bands with highest wavelength are strongly influenced by the above structural changes. The UV-spectra simulations reveal that the introduction of donor groups like para-OMe, para-NMe2, and para-N(H)Ph, which are in n-π conjugation with the aryl moieties, should result in absorption of visible light by the corresponding 1,2-diphospholes, thus making them promising candidates for new functional materials.

Supramolecular Optimization of Sensory Function of a Hemicurcuminoid through Its Incorporation into Phospholipid and Polymeric Polydiacetylenic Vesicles: Experimental and Computational Insight.

This work presents the synthesis of a new representative of hemicurcuminoids with a nonyloxy substituent (HCur) as a fluorescent amphiphilic structural element of vesicular aggregates based on phosphatidylcholine (PC), phosphatidylserine (PS), and 10,12-pentacosadiynoic acid (PCDA). Both X-ray diffraction analysis of the single crystal and 1H NMR spectra of HCur in organic solvents indicate the predominance of the enol-tautomer of HCur. DFT calculations show the predominance of the enol tautomer HCur in supramolecular assemblies with PC, PS, and PCDA molecules. The results of the molecular modeling show that HCur molecules are surrounded by PC and PS with a rather weak exposure to water molecules, while an exposure of HCur molecules to water is enhanced under its supramolecular assembly with PCDA molecules. This is in good agreement with the higher loading of HCur into PC(PS) vesicles compared to PCDA vesicles converted into polydiacetylene (PDA) ones by photopolymerization. HCur molecules incorporated into HCur-PDA vesicles exhibit greater planarity distortion and hydration effect in comparison with HCur-PC(PS) ones. HCur-PDA is presented as a dual fluorescence-chromatic nanosensor responsive to a change in pH within 7.5-9.5, heavy metal ions and polylysine, and the concentration-dependent fluorescent response is more sensitive than the chromatic one. Thus, the fluorescent response of HCur-PDA allows for the distinguishing between Cd2+ and Pb2+ ions in the concentration range 0-0.01 mM, while the chromatic response allows for the selective sensing of Pb2+ over Cd2+ ions at their concentrations above 0.03 mM.

Rationalization of solvation and stabilization of palladium nanoparticles in imidazolium-based ionic liquids by DFT and vibrational spectroscopy.

A combined DFT/vibrational spectroscopy approach is used to determine the interactions of the 1,3-dimethylimidazolium ([Mmim](+)) and 1-ethyl-3-methylimidazolium ([Emim](+)) cations and [BF(4)](-) anions with each other in the liquid state and with Pd nanoparticles (NPs) immersed in ionic liquids (ILs) composed of these ions. Formation of aggregates of the counter-ions in the liquid does not have a strong influence on the interaction energy of the IL components with the palladium clusters used to model NPs, which is smaller than the energy of addition of a Pd atom to the cluster. Stronger Pd-Pd interactions in comparison to the interactions of the palladium cluster with the IL suggest kinetic stabilisation of Pd-NPs in 1,3-dialkylimidazolium tetrafluoroborates rather than thermodynamic stabilisation. Moreover, the palladium clusters interact more strongly with the anions than with the cations, and this suggests an important role of the anions in formation and stabilisation of Pd-NP in ILs. At the same time, binding between an isolated Pd atom and [Mmim](+) cation is stronger than Pd-[BF(4)](-) binding. IR and Raman spectral simulations reveal that surface-enhanced Raman spectroscopy is much less sensitive to interactions of Pd-NPs with the [BF(4)](-) anion compared to interactions with [Mmim](+) cations. In contrast, IR spectroscopy is better suited to study the anion-metal interactions, whereas IR spectral manifestations of the cation-metal interactions are rather modest. The splitting of the strong ν(as)(BF(4)(-)) IR band into three components appears to be a convenient spectroscopic marker for Pd-[BF(4)](-) interactions, which is confirmed by actual spectra of Pd-NPs stabilised by [Emim][BF(4)]. The IR spectra and their assignment with quantum chemical computations suggest that both the anions and cations of [Emim][BF(4)] interact with the Pd-NP surface in the IL. The cation ring orientation close to the surface normal appears to be the dominant interaction. The anion is bound to the surface through either two or three fluorine atoms.