Pyridine Dimer Research Articles

Molecular Association and Reactivity of the Pyridine Dimer Cation.

A recent experimental report has identified the formation of the C-N hemibonded pyridine dimer cation following vacuum ultraviolet near-threshold photoionization [J. Phys. Chem. Lett., 2021, 12, 4936-4943]. Herein, the dynamics and consequent reactivity of the pyridine dimer cation were investigated employing Born-Oppenheimer molecular dynamics (BOMD) simulations. An antiparallel π-stacked pyridine dimer in the neutral ground state is transformed into a noncovalently interacting C-H···N hydrogen-bonded structure which can lead to proton transfer in the cationic state. Additionally, C-N- and N-N-bonded adducts were formed in the cationic state. Further, metastable C-H···H-C-bonded cationic species was observed, which rearranged to an N-N bonded adduct. In contrast to the experimental observation, migration of the proton to the α position was not observed in the C-N bonded adduct owing to a high barrier of about 2 eV. The observed trends in the molecular association, proton transfer, and the formation of C-N and N-N bonded adducts are a consequence of the roaming dynamics of one pyridine moiety over the other in the cationic state.

Synthesis, spectroscopic characterizations, photophysical properties and DFT studies of a novel iridium(III) complex containing 2-(2-butoxy-4-fluorophenyl)pyridine ligand

The iridium(III) complex, Ir(bFppy)2(pyim) (bFppy = 2-(2-butoxy-4-fluorophenyl)pyridine and pyim = 2-(1H-Imidazol-2-yl)pyridine) was excellently prepared between 2-(1H-Imidazol-2-yl)pyridine and chloro-bridged iridium(III) dimer via reflux reaction. Butoxy functional group and fluorine atom were added to the phenyl ring of 2-phenylpyridine at positions 2 and 4 respectively, as cyclometalating ligand. The Ir(bFppy)2(pyim) complex was characterized by spectroscopic methods: FTIR, NMR, LCMS and UV–Vis absorption. The presence of two sharp peaks at 1256 cm−1 and 1129 cm−1 due to ν(CO) was revealed by IR analysis. The bands appear in the range of 1594–1567 cm−1 owing to the CC and CN aromatic ring stretching vibrations of phenyl and pyridine. The 1H NMR spectrum showed signals in the range of δ 5.50–8.60 ppm corresponding to phenylpyridine and pyridylimidazole protons. In contrast, the proton signals in the range of δ 0.80–4.50 ppm, assignable to butyl substituent. The UV–Vis spectrum displayed weaker and broader bands (333 nm and 376 nm) in the visible region due to the spin-forbidden 3MLCT transitions. The steady-state emission spectrum of the Ir(bFppy)2(pyim) complex in air-equilibrated methylene chloride solution at 298 K exhibited almost blue emission with a λmax at 466 nm. To support the experimental spectroscopic data, DFT and TD-DFT measurements were conducted using B3LYP in combination with the LanL2DZ basis set. The chemical shifts, vibrational modes and maximum absorptions of the Ir(bFppy)2(pyim) complex were relatively well reproduced.

Pyridine Dimers and Their Low-Temperature Isomerization: A High-Resolution Matrix-Isolation Spectroscopy Study.

The bonding between two neutral aromatic compounds, especially small ones, has been controversially debated in the last decades, and terms like "π-stacking" had to be revised. Surprisingly, despite of many experimental and computational work, there is still no clear consensus about the structure of and the bonding in the pyridine dimer. In this work, for different isomeric forms of the pyridine dimer, the structures and bonding were elucidated by combining high-resolution matrix-isolation spectroscopic results with quantum-chemical calculations. High-resolution IR spectra of Ne matrices at 4 K containing pyridine were recorded for different concentrations and upon annealing to 10 and 12 K, relying on three isotopologues of pyridine. The spectra show the presence of hydrogen-bonded, T-shaped, and stacked forms of weakly-bound pyridine dimers. Among these, the hydrogen-bonded isomer is identified as the lowest-energy form. The results provide for the first time conclusive information about the interaction between two pyridine dimers.

Pyridine Dimers and Their Low‐Temperature Isomerization: A High‐Resolution Matrix‐Isolation Spectroscopy Study

AbstractThe bonding between two neutral aromatic compounds, especially small ones, has been controversially debated in the last decades, and terms like “π‐stacking” had to be revised. Surprisingly, despite of many experimental and computational work, there is still no clear consensus about the structure of and the bonding in the pyridine dimer. In this work, for different isomeric forms of the pyridine dimer, the structures and bonding were elucidated by combining high‐resolution matrix‐isolation spectroscopic results with quantum‐chemical calculations. High‐resolution IR spectra of Ne matrices at 4 K containing pyridine were recorded for different concentrations and upon annealing to 10 and 12 K, relying on three isotopologues of pyridine. The spectra show the presence of hydrogen‐bonded, T‐shaped, and stacked forms of weakly‐bound pyridine dimers. Among these, the hydrogen‐bonded isomer is identified as the lowest‐energy form. The results provide for the first time conclusive information about the interaction between two pyridine dimers.

Noncovalent Interactions from Models for the Møller-Plesset Adiabatic Connection.

Given the omnipresence of noncovalent interactions (NCIs), their accurate simulations are of crucial importance across various scientific disciplines. Here we construct accurate models for the description of NCIs by an interpolation along the Møller–Plesset adiabatic connection (MP AC). Our interpolation approximates the correlation energy, by recovering MP2 at small coupling strengths and the correct large-coupling strength expansion of the MP AC, recently shown to be a functional of the Hartree–Fock density. Our models are size consistent for fragments with nondegenerate ground states, have the same cost as double hybrids, and require no dispersion corrections to capture NCIs accurately. These interpolations greatly reduce large MP2 errors for typical π-stacking complexes (e.g., benzene–pyridine dimers) and for the L7 data set. They are also competitive with state-of-the-art dispersion enhanced functionals and can even significantly outperform them for a variety of data sets, such as CT7 and L7.

CRASY: correlated rotational alignment spectroscopy of pyridine. The rotational Raman spectrum of pyridine and asymmetric fragmentation of pyridine dimer cations.

We investigated the rotational Raman spectrum of pyridine monomers and pyridine dimers with mass-correlated rotational alignment spectroscopy (mass-CRASY) and ab initio calculations. The mass spectrum showed a strong signal for the protonated pyridine cation, which we assigned to asymmetric fragmentation of the dimer: ab initio calculations revealed facile proton transfer in the dimer cation and thermodynamically favorable asymmetric fragmentation. In the rotational spectrum correlated to the monomer mass channel, we assigned up to 40 lines for rotational states J ≤ 8. No spectrum could be assigned for the dimer, possibly due to the theoretically predicted presence of multiple dimer structures.

Understanding the Behavior of π–π Interactions in Crystal Structures in Light of Geometry Corrected Statistical Analysis: Similarities and Differences with the Theoretical Models

Statistical analyses on π–π interactions among benzenoid dimers and pyridinoid dimers have been performed. The population distributions in these analyses are not in accordance with the theoretical study on benzene dimers and pyridine dimers. A geometrical correction has been proposed and incorporated into the statistical analysis, and then the population distributions have been compared with the theoretical models. The preferred interplanar angles, interplanar distances, offset distances, offset directions, and relative orientation of the pyridyl ring in the T-shaped geometry and relative orientation of the dipoles of two pyridyl rings have been evaluated from the geometry-corrected population distribution. Interestingly, all these parameters are in good agreement with the geometries predicted in a theoretical study. In addition, this analysis also reveals the presence of a small offset in the T-shaped geometry of pyridinoid dimers, which was overlooked in the theoretical study.

Influence of hydrogen bonds on edge-to-face interactions between pyridine molecules

Edge-to-face interactions between two pyridine molecules and the influence of simultaneous hydrogen bonding of one or both of the pyridines to water on those interactions were studied by analyzing data from ab initio calculations. The results show that the edge-to-face interactions of pyridine dimers that are hydrogen bonded to water are generally stronger than those of non-H-bonded pyridine dimers, especially when the donor pyridine forms a hydrogen bond. The binding energy of the most stable edge-to-face interacting H-bonded pyridine dimer is -5.05kcal/mol, while that for the most stable edge-to-face interacting non-H-bonded pyridine dimer is -3.64kcal/mol. The interaction energy data obtained in this study cannot be explained solely by the differences in electrostatic potential between pyridine and the pyridine-water dimer. However, the calculated cooperative effect can be predicted using electrostatic potential maps.

Discovering the stacking landscape of a pyridine-pyridine system

Extremely extensive calculations of potential energy surfaces for the parallel-displaced configuration of pyridine dimer systems have been carried out using a dispersion-corrected density functional. Instead of focusing on stationary geometries these calculations provide much deeper insight into the “landscape” of the interaction energies of the particular systems—one can learn how the pyridine dimer stability changes along with various geometrical parameters. Other calculations such as natural bond orbital and energy decomposition have also been applied. The interplay of two significant factors, electrostatic forces and electron correlation effects, have been evaluated. The role of π···π interactions in the stacked pyridine systems has also been confirmed, and surprisingly, this happened to be true even for the geometries where the formation of C-H···π interactions might be proposed instead. The combination of many different methods has revealed the complexity of the stacking interactions. Apart from providing a “literal new look” into pyridine interaction patterns another picture has emerged. A stacking interaction in a pyridine dimer system is perceived as a combination of many different sources of the interaction energy, including orbital ones, and this is true for many different geometries.

ESI-MS of Cucurbituril Complexes Under Negative Polarity.

Electrospray ionization mass spectrometry (ESI-MS) is a powerful tool to study host-guest supramolecular interactions. ESI-MS can be used for detailed gas-phase reactivity studies, to clarify the structure, or simply to verify the formation of complexes. Depending on the structure of the host and of the guest, negative and/or positive ESI are used. Here we report the unexpected formation of host-guest complexes between cucurbit[n]urils (n = 7, 8, CB[n]) and amine, styryl pyridine, and styryl pyridine dimer cations, under negative ESI. Non-complexed CB[n] form double charged halide (Br-, Cl-, F-) adducts. Under negative ESI, halide ions interact with CB[n] outer surface hydrogen atoms. One to one host-guest complexes (1:1) of CB[n] with positive charged guests were also observed as single and double charged ions under negative ESI. The positive charge of guests is neutralized by ion-pairing with halide anions. Depending on the number of positive charges guests retain in the gas phase, one or two additional halide ions are required for neutralization. Complexes 1:2 of CB[8] with styryl pyridines retain two halide ions in the gas phase, one per guest. Styryl pyridine dimers form 1:1 complexes possessing a single extra halide ion and therefore a single positive charge. Negative ESI is sensitive to small structural differences between complexes, distinguishing between 1:2 complexes of styryl pyridine-CB[8] and corresponding 1:1 complexes with the dimer. Negative ESI gives simpler spectra than positive ESI and allows the determination of guest charge state of CB[n] complexes in the gas phase. Graphical Abstract ᅟ.

Ab Initio Atom-Atom Potentials Using CamCASP: Theory and Application to Many-Body Models for the Pyridine Dimer.

Creating accurate, analytic atom-atom potentials for small organic molecules from first principles can be a time-consuming and computationally intensive task, particularly if we also require them to include explicit polarization terms, which are essential in many systems. We describe how the CamCASP suite of programs can be used to generate such potentials using some of the most accurate electronic structure methods currently applicable. We derive the long-range terms from monomer properties and determine the short-range anisotropy parameters by a novel and robust method based on the iterated stockholder atom approach. Using these techniques, we develop distributed multipole models for the electrostatic, polarization, and dispersion interactions in the pyridine dimer and develop a series of many-body potentials for the pyridine system. Even the simplest of these potentials exhibits root mean square errors of only about 0.6 kJ mol(-1) for the low-energy pyridine dimers, significantly surpassing the best empirical potentials. Our best model is shown to support eight stable minima, four of which have not been reported before in the literature. Further, the functional form can be made systematically more elaborate so as to improve the accuracy without a significant increase in the human-time spent in their generation. We investigate the effects of anisotropy, rank of multipoles, and choice of polarizability and dispersion models.

Synthesis of novel anticancer ruthenium–arene pyridinylmethylene scaffolds via three-component reaction

A novel three components approach for the synthesis of bioactive Ru–arene pyridinylmethylene complexes has been developed using pyridine carboxaldehyde, amino pyridine and dichloro (p-cymene) ruthenium(II) dimer as starting materials. These scaffolds were screened for their anticancer activity against breast cancer (MCF7) and human Epitheloid Cervix Carcinoma (HeLa) cell line. It was established that compounds [(η6-pcymene)RuCl(κ2-N,N-(3,5-dinitro-pyridin-2-yl)-pyridin-2-ylmethylene-amine)]PF6 (4o), [(η6-pcymene)RuCl(κ2-N,N-N-(3,5-dibromo-pyridin-2-yl)-pyridin-2-ylmethylene-amine)]PF6 (4c), [(η6-pcymene)RuCl(κ2-N,N-(3,5-dibromo-6-methylpyridin-2-yl)-pyridin-2-ylmethylene-amine)]PF6 (4j) and [(η6-pcymene)RuCl(κ2-N,N-3(3-bromo-5-methyl-pyridin-2-yl)-pyridin-2-ylmethylene-amine)]PF6 (4b) were significantly active against both the cell lines.

Ab initio study of the π–π interaction in the pyridine dimer: Effects of bond functions

A systematic ab initio study was carried out to investigate the π–π intermolecular interaction in the pyridine dimer. Potential energy curves were calculated for eight major configurations at second-order Møller–Plesset approximation (MP2) using various large basis sets augmented with bond functions. The basis set superposition error (BSSE) was considered by the counterpoise method. The study shows that bond functions can effectively give accurate description of π–π interactions. The intermolecular energies at the MP2 potential minima of the eight configurations were recalculated using the coupled-cluster method including single, double, and perturbative triple configurations, CCSD(T), with the aug-cc-pVDZ basis set augmented with the bond functions {6s6p4d2f}. Two most stable geometries were found to be antiparallel-displaced, with the CCSD(T) interaction energies of −3.05 and −2.95kcal/mol, respectively. The CCSD(T) interaction energies of other configurations were found to be −1.05, −2.30, −1.42, −2.29, −1.79, and −1.83kcal/mol, respectively. Dispersion is largely responsible for attraction in the pyridine dimer and, as a result, electron correlation beyond MP2 is necessary as in the case of heteroaromatic molecules.

Selective uncaging of DNA through reaction rate selectivity.

The synthesis and use of the new nucleobase-caged nucleotides dT(pHP) and dT(NDEACM) is reported. Through a combination of time and wavelength selectivity four levels of selective uncaging with only two cages, and only two wavelengths, were obtained. The new residue dT(pHP) can be uncaged at 313 nm without the formation of unwanted cyclic pyridine dimers.

Hydrogen Bonded Pyridine Dimer: A Possible Intermediate in the Electrocatalytic Reduction of Carbon Dioxide to Methanol

Previously, electrogenerated pyridinyl was implicated as a catalyst for the reduction of CO2 to methanol. However, recent quantum mechanical calculations of both the homogeneous redox potential for the pyridinium/pyridinyl redox couple (900 mV more negative than experimentally reported) and the pKa of the reduced pyridinyl species (~27) have led to the proposal that the homogeneous reduction of pyridinium does not play a role in the observed catalytic reduction of CO2 to methanol. In contrast, a more complete consideration of the reaction including the realization that pyridinium reduction is tightly coupled to H2 evolution, produces a calculated redox potential in agreement with the experimental findings. In reexamining this system, it is found that aqueous solutions containing a near equimolar mixture of pyridine and pyridinium (i.e., solution pH near the pyridinium pKa = 5.2) contain a substantial concentration of a hydrogen-bonded dimer formed by the generation of a N-H•••N bond containing one strong NH bond and one elongated NH bond. This species has been identified by X-ray diffraction of crystals grown in aqueous media from pyridine/pyridinium mixtures, and can be observed directly in solution using Raman spectroscopy. DFT (density functional theory) calculations indicate that the pKa for this species is ~22, a value that is consistent with a proton exchange capability. This suggests that this hydrogen bonded dimer may be the pre-electrocatalyst for the observed activation of CO2.

Ab initio study of the structure and energetic of pyridine dimers

Abstract Strong correlation of stabilization energies of π-stacked pyridine and fluorinated pyridine dimers with various relative orientations is presented. Four possible orientations of the monomers were considered. A SAPT decomposition of the interaction energies is presented and briefly discussed. The dominant electrostatic contribution to the stabilization energy is found in some dimers and its possible origin is addressed in the discussion. An outline of possible future studies is introduced.

Effects of Aromatic Trifluoromethylation, Fluorination, and Methylation on Intermolecular π–π Interactions

Marcus theory states that the rate of charge transfer is directly proportional to the amount of intermolecular orbital overlap. Theoretically optimizing the electronic coupling through the orientation and distance which both can increase the frontier orbital overlap between molecules is an attractive route to potentially provide theoretical insight for discovering new high performance semiconductor materials. To investigate how these parameters qualitatively affect charge transfer of model systems, unconstrained dimer optimizations with MP2 and dispersion-corrected DFT methods were used to probe the π-π interactions of methylated, fluorinated, and trifluoromethylated benzene, pyridine, and bipyridine dimers. These systems can serve as simplified models representing weak noncovalent interactions in organic semiconductor materials. Enhanced intermolecular interaction energies, reduced π-π distances, and more favorable cofacial orientations were found with the trifluoromethylated dimers compared to fluorinated and methylated dimers studied. Similar effects were found with donor-acceptor pairs that represent organic p-n heterojunction systems. These enhanced π-π interactions are likely caused by increased molecular quadrupole moment and dispersion interaction associated with trifluoromethylation. This computational study illustrates the strong potential of trifluoromethylation and, possibly perfluoroalkylation of acenes and heteroacenes, leading qualitatively to enhanced electron transfer through better π-π stacked structures, making them viable candidates for use as n-type organic semiconductor materials. The findings also provide insight for fundamental interactions between drug molecules that include fluorinated and trimethylfluorinated aromatics binding to protein receptors.

Parallel Interactions at Large Horizontal Displacement in Pyridine–Pyridine and Benzene–Pyridine Dimers

A study of crystal structures from the Cambridge Structural Database (CSD) and DFT calculations reveals that parallel pyridine-pyridine and benzene-pyridine interactions at large horizontal displacements (offsets) can be important, similar to parallel benzene-benzene interactions. In the crystal structures from the CSD preferred parallel pyridine-pyridine interactions were observed at a large horizontal displacement (4.0-6.0 Å) and not at an offset of 1.5 Å with the lowest calculated energy. The calculated interaction energies for pyridine-pyridine and benzene-pyridine dimers at a large offset (4.5 Å) are about 2.2 and 2.1 kcal mol(-1), respectively. Substantial attraction at large offset values is a consequence of the balance between repulsion and dispersion. That is, dispersion at large offsets is reduced, however, repulsion is also reduced at large offsets, resulting in attractive interactions.

Energy Component Analysis of π Interactions

Fundamental features of biomolecules, such as their structure, solvation, and crystal packing and even the docking of drugs, rely on noncovalent interactions. Theory can help elucidate the nature of these interactions, and energy component analysis reveals the contributions from the various intermolecular forces: electrostatics, London dispersion terms, induction (polarization), and short-range exchange-repulsion. Symmetry-adapted perturbation theory (SAPT) provides one method for this type of analysis. In this Account, we show several examples of how SAPT provides insight into the nature of noncovalent π-interactions. In cation-π interactions, the cation strongly polarizes electrons in π-orbitals, leading to substantially attractive induction terms. This polarization is so important that a cation and a benzene attract each other when placed in the same plane, even though a consideration of the electrostatic interactions alone would suggest otherwise. SAPT analysis can also support an understanding of substituent effects in π-π interactions. Trends in face-to-face sandwich benzene dimers cannot be understood solely in terms of electrostatic effects, especially for multiply substituted dimers, but SAPT analysis demonstrates the importance of London dispersion forces. Moreover, detailed SAPT studies also reveal the critical importance of charge penetration effects in π-stacking interactions. These effects arise in cases with substantial orbital overlap, such as in π-stacking in DNA or in crystal structures of π-conjugated materials. These charge penetration effects lead to attractive electrostatic terms where a simpler analysis based on atom-centered charges, electrostatic potential plots, or even distributed multipole analysis would incorrectly predict repulsive electrostatics. SAPT analysis of sandwich benzene, benzene-pyridine, and pyridine dimers indicates that dipole/induced-dipole terms present in benzene-pyridine but not in benzene dimer are relatively unimportant. In general, a nitrogen heteroatom contracts the electron density, reducing the magnitude of both the London dispersion and the exchange-repulsion terms, but with an overall net increase in attraction. Finally, using recent advances in SAPT algorithms, researchers can now perform SAPT computations on systems with 200 atoms or more. We discuss a recent study of the intercalation complex of proflavine with a trinucleotide duplex of DNA. Here, London dispersion forces are the strongest contributors to binding, as is typical for π-π interactions. However, the electrostatic terms are larger than usual on a fractional basis, which likely results from the positive charge on the intercalator and its location between two electron-rich base pairs. These cation-π interactions also increase the induction term beyond those of typical noncovalent π-interactions.

Effect of acceptor heteroatoms on π-hydrogen bonding interactions: A study of indole⋅⋅⋅thiophene heterodimer in a supersonic jet

Resonant two photon ionization (R2PI), IR-UV, and UV-UV double resonance spectroscopic techniques combined with quantum chemistry calculations have been used to determine the structure of indole···thiophene dimer observed in a supersonic jet. With the help of combined experimental and theoretical IR spectra it has been found that the observed dimer has a N-H···π hydrogen bonded slanted T-shaped structure. The present study demonstrates the effect of heteroatoms present in the acceptors on the strength of the π-hydrogen bonding interactions. It was concluded by Sherrill and co-workers from their theoretical study of benzene···pyridine dimer that aromatic rings containing heteroatoms are poorest π-hydrogen bond acceptors [E. G. Hohenstein and C. D. Sherrill, J. Phys. Chem. A 113, 878 (2009)]. But the current spectroscopic investigation exhibits that five membered aromatic heterocycles are favorable π-hydrogen bond acceptors. In this study, it has also been shown that thiophene is a better π-hydrogen bond acceptor than furan. The present work has immense biological significance as indole is the chromophore of tryptophan residue in the proteins and thiophene derivatives have potential therapeutic applications. Thus, understanding the binding motif between indole and thiophene in the heterodimer studied in this work may help in designing efficient drugs.