Pyrrole Dimer Research Articles

Accuracy of projected atomic virtual orbital space in embedding applications

ABSTRACT The performance of the recently suggested projected atomic orbitals (PAO) approach as the virtual space in excited state projection-based embedding applications is analysed. The role of the parameters in the PAO generation is discussed and the impact of different choices is evaluated on the ground state of the stacked formaldehyde and pyrrole dimers. A comparison of excitation energies obtained with PAOs and localised virtual orbitals is given and the role of diffuse basis functions is discussed using a benchmark set from previous studies.

Internal Energy Dependence of the Pyrrole Dimer Cation Structures Formed in a Supersonic Plasma Expansion: Charge-Resonance and Hydrogen-Bonded Isomers.

The structures of the pyrrole dimer cation (Py2+) formed in an electron-ionization-driven supersonic plasma expansion of Py seeded in Ar or N2 are probed as a function of its internal energy by infrared photodissociation (IRPD) spectroscopy in a tandem mass spectrometer. The IRPD spectra recorded in the CH and NH stretch ranges are analyzed by dispersion-corrected density functional theory (DFT) calculations at the B3LYP-D3/aug-cc-pVTZ level. The spectra of the cold Ar/N2-tagged Py2+ clusters, Py2+Ln (n = 1-5 for Ar, n = 1 for N2), indicate the exclusive formation of the most stable antiparallel π-stacked Py2+ structure under cold conditions, which is stabilized by charge-resonance interaction. The bare Py2+ dimers produced in the ion source have higher internal energy, and the observation of additional transitions in their IRPD spectra suggests a minor population of less stable hydrogen-bonded isomers composed of heterocyclic Py/Py+ structures formed after intramolecular H atom transfer and ring opening. These intermolecular isomers differ from the chemically bonded structures proposed earlier in the analysis of IRPD spectra of Py2+ generated by VUV ionization of neutral Pyn clusters.

Comparison of approximate intermolecular potentials for ab initio fragment calculations on medium sized N-heterocycles.

The ground state intermolecular potential of bimolecular complexes of N‐heterocycles is analyzed for the impact of individual terms in the interaction energy as provided by various, conceptually different theories. Novel combinations with several formulations of the electrostatic, Pauli repulsion, and dispersion contributions are tested at both short‐ and long‐distance sides of the potential energy surface, for various alignments of the pyrrole dimer as well as the cytosine–uracil complex. The integration of a DFT/CCSD density embedding scheme, with dispersion terms from the effective fragment potential (EFP) method is found to provide good agreement with a reference CCSD(T) potential overall; simultaneously, a quantum mechanics/molecular mechanics approach using CHELPG atomic point charges for the electrostatic interaction, augmented by EFP dispersion and Pauli repulsion, comes also close to the reference result. Both schemes have the advantage of not relying on predefined force fields; rather, the interaction parameters can be determined for the system under study, thus being excellent candidates for ab initio modeling.

Confinement inside a Crystalline Sponge Induces Pyrrole To Form N-H⋅⋅⋅π Bonded Tetramers.

Based on the DFT-level-calculated molecular volume (Vmol ) of pyrrole and its liquid density, pyrrole manifests the highest liquid density coefficient LDc (defined as [Vmol ×density ×0.6023]/FW) value of 0.7. Normal liquids have LDc <0.63. This very high LDc is due to the strong N-H⋅⋅⋅π interactions in solution, and hence pyrrole can be considered to be a pseudo-crystalline liquid. When trapped inside the confined space of a crystalline sponge, a reorientation of the N-H⋅⋅⋅π interaction is observed leading to specific cyclic N-H⋅⋅⋅π tetramers and N-H⋅⋅⋅π dimers, as verified by single-crystal X-ray crystallographic and computational methods. These tetramers are of the same size as four pyrrole molecules in the solid-state of pyrrole, yet the cyclic N-H⋅⋅⋅π intermolecular interactions are circularly oriented instead of being in the linear zigzag structure found in the X-ray structure of a solid pyrrole. The confinement thus acts as an external driving force for tetramer formation.

Electron transfer in photoexcited pyrrole dimers.

Following on from previous experimental and theoretical work [Neville et al., Nat. Commun. 7, 11357 (2016)], we report the results of a combined electronic structure theory and quantum dynamics study of the excited state dynamics of the pyrrole dimer following excitation to its first two excited states. Employing an exciton-based analysis of the Ã(π3s/σ*) and B̃(π3s/3p/σ*) states, we identify an excited-state electron transfer pathway involving the coupling of the Ã(π3s/σ*) and B̃(π3s/3p/σ*) states and driven by N-H dissociation in the B̃(π3s/3p/σ*) state. This electron transfer mechanism is found to be mediated by vibronic coupling of the B̃ state, which has a mixed π3s/3p Rydberg character at the Franck-Condon point, to a high-lying charge transfer state of the πσ* character by the N-H stretch coordinate. Motivated by these results, quantum dynamics simulations of the excited-state dynamics of the pyrrole dimer are performed using the multiconfigurational time-dependent Hartree method and a newly developed model Hamiltonian. It is predicted that the newly identified electron transfer pathway will be open following excitation to both the Ã(π3s/σ*) and B̃(π3s/3p/σ*) states and may be the dominant relaxation pathway in the latter case.

Accurate interaction energies by spin component scaled Möller-Plesset second order perturbation theory calculations with optimized basis sets (SCS-MP2mod): Development and application to aromatic heterocycles.

The Spin Component Scaled (SCS) MP2 method using a reduced and optimized basis set (SCS-MP2mod) is employed to compute the interaction energies of nine homodimers, formed by aromatic heterocyclic molecules (pyrrole, furan, thiophene, oxazole, isoxazole, pyridine, pyridazine, pyrimidine, and pyrazine). The coefficients of the same-spin and opposite-spin correlation energies and the Gaussian type orbitals (GTO) polarization exponents of the 6-31G** basis set are simultaneously optimized in order to minimize the energy differences with respect to the coupled-cluster with single, double and perturbative triples excitations [CCSD(T)] reference interaction energies, extrapolated to a complete basis set. It is demonstrated that the optimization of the spin scale factors leads to a noticeable improvement of the accuracy with a root mean square deviation less than 0.1 kcal/mol and a largest unsigned deviation smaller than 0.25 kcal/mol. The pyrrole dimer provides an exception, with a slightly higher deviation from the reference data. Given the high benefit in terms of computational time with respect to the CCSD(T) technique and the small loss of accuracy, the SCS-MP2mod method appears to be particularly suitable for extensive sampling of intermolecular potential energy surfaces at a quantum mechanical level. Within this framework, a transferability test of the SCS-MP2mod parameters to a benchmark set of this class of molecules is very promising as the reference interaction energies of several heterocyclic aromatic heterodimers were reproduced with a standard deviation of 0.30 kcal/mol. The SCS-MP2mod remarkably outperforms the value of 1.95 kcal/mol obtained with standard MP2/6-31G**.

Aromatic Charge Resonance Interaction Probed by Infrared Spectroscopy

AbstractCharge resonance is a strong attractive intermolecular force in aromatic dimer radical ions. Despite its importance, this fundamental interaction has not been characterized at high resolution by spectroscopy of isolated dimers. We employ vibrational infrared spectroscopy of cold aromatic pyrrole dimer cations to precisely probe the charge distribution by measuring the frequency of the isolated N−H stretch mode (νNH). We observe a linear correlation between νNH and the partial charge q on the pyrrole molecule in different environments. Subtle effects of symmetry reduction, such as substitution of functional groups (here pyrrole replaced by N‐methylpyrrole) or asymmetric solvation (here by an inert N2 ligand), shift the charge distribution toward the moiety with lower ionization energy. This general approach provides a precise experimental probe of the asymmetry of the charge distribution in such aromatic homo‐ and heterodimer cations.

Aromatic Charge Resonance Interaction Probed by Infrared Spectroscopy.

Charge resonance is a strong attractive intermolecular force in aromatic dimer radical ions. Despite its importance, this fundamental interaction has not been characterized at high resolution by spectroscopy of isolated dimers. We employ vibrational infrared spectroscopy of cold aromatic pyrrole dimer cations to precisely probe the charge distribution by measuring the frequency of the isolated N-H stretch mode (νNH ). We observe a linear correlation between νNH and the partial charge q on the pyrrole molecule in different environments. Subtle effects of symmetry reduction, such as substitution of functional groups (here pyrrole replaced by N-methylpyrrole) or asymmetric solvation (here by an inert N2 ligand), shift the charge distribution toward the moiety with lower ionization energy. This general approach provides a precise experimental probe of the asymmetry of the charge distribution in such aromatic homo- and heterodimer cations.

Pyrrole multimers and pyrrole-acetylene hydrogen bonded complexes studied in N2 and para-H2 matrixes using matrix isolation infrared spectroscopy and ab initio computations

Hydrogen bonded interaction of pyrrole multimer and acetylene-pyrrole complexes were studied in N2 and p-H2 matrixes. DFT computations showed T-shaped geometry for the pyrrole dimer and cyclic complex for the trimer and tetramer were the most stable structures, stabilized by NH⋯π interactions. The experimental vibrational wavenumbers observed in N2 and p-H2 matrixes for the pyrrole multimers were correlated with the computed wavenumbers. Computations performed at MP2/aug-cc-pVDZ level of theory showed that C2H2 and C4H5N forms 1:1 hydrogen-bonded complexes stabilized by CH⋯π interaction (Complex A), NH⋯π interaction (Complex B) and π⋯π interaction (Complex C), where the former complex is the global minimum and latter two complexes were the first and second local minima, respectively. Experimentally, 1:1 C2H2C4H5N complexes A (global minimum) and B (first local minimum) were identified from the shifts in the NH stretching, NH bending, CH bending region of pyrrole and CH asymmetric stretching and bending region of C2H2 in N2 and p-H2 matrixes. Computations were also performed for the higher complexes and found two minima corresponding to the 1:2 C2H2C4H5N and three minima for the 2:1 C2H2C4H5N complexes. Experimentally the global minimum 1:2 and 2:1 C2H2C4H5N complexes were identified in N2 and p-H2 matrixes.

Synthesis of pyrrole-imidazole polyamide oligomers based on a copper-catalyzed cross-coupling strategy

Pyrrole-imidazole (Py-Im) polyamides are useful tools for chemical biology and medicinal chemistry studies due to their unique binding properties to the minor groove of DNA. We developed a novel method of synthesizing Py-Im polyamide oligomers based on a Cu-catalyzed cross-coupling strategy. All four patterns of dimer fragments could be synthesized using a Cu-catalyzed Ullmann-type cross-coupling with easily prepared monomer units. Moreover, we demonstrated that pyrrole dimer, trimer, and tetramer building blocks for Py-Im polyamide synthesis were accessible by combining site selective iodination of the pyrrole/pyrrole coupling adduct.

Identification of a new electron-transfer relaxation pathway in photoexcited pyrrole dimers.

Photoinduced electron transfer is central to many biological processes and technological applications, such as the harvesting of solar energy and molecular electronics. The electron donor and acceptor units involved in electron transfer are often held in place by covalent bonds, π–π interactions or hydrogen bonds. Here, using time-resolved photoelectron spectroscopy and ab initio calculations, we reveal the existence of a new, low-energy, photoinduced electron-transfer mechanism in molecules held together by an NH⋯π bond. Specifically, we capture the electron-transfer process in a pyrrole dimer, from the excited π-system of the donor pyrrole to a Rydberg orbital localized on the N-atom of the acceptor pyrrole, mediated by an N–H stretch on the acceptor molecule. The resulting charge-transfer state is surprisingly long lived and leads to efficient electronic relaxation. We propose that this relaxation pathway plays an important role in biological and technological systems containing the pyrrole building block.

The intricacies of the stacking interaction in a pyrrole–pyrrole system

Extensive calculations of potential energy surfaces for parallel-displaced configurations of pyrrole–pyrrole systems have been carried out by the use of a dispersion-corrected density functional. System geometries associated with the energy minima have been found. The minimum interaction energy has been calculated as −5.38 kcal/mol. However, bonding boundaries appeared to be relatively broad, and stacking interactions can be binding even for ring centroid distances larger than 6 A. Though the contribution of the correlation energy to intermolecular interaction in pyrrole dimers appeared to be relatively small (around 1.6 smaller than it is in a benzene–benzene system), this system’s minimum interaction energy is lower than those calculated for benzene–benzene, benzene–pyridine and even pyridine–pyridine configurations. The calculation of the charges and energy decomposition analysis revealed that the specific charge distribution in a pyrrole molecule and its relatively high polarization are the significant source of the intermolecular interaction in pyrrole dimer systems.

A chiral "Siamese-Twin" calix[4]pyrrole tetramer.

We describe our results in the attempted template syntheses of oligomacrocycle calix[4]pyrrole dimer 4, using Hay coupling reaction conditions, tetraalkynyl calix[4]pyrrole 5 as starting material and two bipyridyl N-oxides of different length as templates. We found that the short bis-N-oxide 3 was not an efficient template for the macrocyclization reaction producing an insoluble crude reaction mixture containing exclusively oligomerization and polycondensation products. On the other hand, when we used the long bis-N-oxide 6 as template we obtained a soluble crude reaction mixture in which we did not detect the expected calix[4]pyrrole dimer 4. Instead, we isolated, in low yield, an encapsulation complex of the bis-N-oxide 6 in a partially reacted calix[4]pyrrole dimer. The major isolated species was an unprecedented calix[4]pyrrole tetramer encapsulating two molecules of 6. The complex adopted a chiral helical-like conformation in the solid state resembling the previously described so-called "Siamese-Twin porphyrins".

The self-associating behavior of pyrrole in liquid xenon

The self-associating behavior of pyrrole in liquid xenon was investigated by analyzing a data set of 185–113 infrared spectra obtained for different concentrations recorded at a constant temperature of 203 K. Analysis of the data using a recently developed least-squares approach allows the vibrational spectra of the monomer and of the different oligomers to be isolated. Apart from the monomer transitions, intense absorption bands originating from pyrrole trimers are observed in almost every spectral region including regions for which no data have yet been reported. Apart from these bands, weak features proving the presence of pyrrole dimer and pyrrole tetramer in the solutions are also reported. The weak character of the dimer bands observed and the low concentrations of these species deduced are explained by the fact that the cryosolutions studied are in chemical equilibrium and by the fact that due to strong cooperative effect present in the trimer, the complexation equilibria are strongly shifted towards the latter species, thereby strongly reducing the equilibrium concentrations of dimer and tetramer.

Alternative biomarkers of n-hexane exposure: Characterization of aminoderived pyrroles and thiol-pyrrole conjugates in urine of rats exposed to 2,5-hexanedione

The identification of pyrrole derivatives in urine of rats exposed to 2,5-hexanedione (2,5-HD), was performed to select an adequate peripheral biomarker predictive of 2,5-HD neurotoxicity. Studies on molecular mechanism of 2,5-HD neurotoxicity have revealed that 2,5-hexanedione reacts with free amino groups of lysine in proteins forming primary pyrrole adducts, which may autoxidize and form pyrrole dimers, responsible for protein crosslinking in neurofilaments, or react with sulfhydryl groups of cysteine in peptides and proteins, forming secondary pyrrole adducts, which probably may inhibit the process responsible by 2,5-HD neurotoxicity. In this work, the analysis of excreted 2,5-HD and pyrrole derivatives in urine of rats i.p. treated with 3 doses of 2,5-HD (400mg/kg bw/48h) was performed using ESI-LC–MS/MS. Several pyrrole compounds were identified, namely dimethylpyrrole norleucine (DMPN), cysteine-pyrrole conjugate (DMPN NAC), glutathione-pyrrole conjugate (DMPN GSH) and 2,5-dimethylpyrrole (2,5-DMP). Additionally, free and total 2,5-HD, DMPN and DMPN NAC were quantified. The observed results suggest that DMPN is a sensitive and specific indicator of repeated exposure to 2,5-HD.

Structure of the Indole−Benzene Dimer Revisited

The structure of the indole-benzene dimer has been investigated using experimental techniques, namely, UV spectroscopy and infrared-ultraviolet (IR/UV) double resonance spectroscopy, combined with quantum chemical calculations such as MP2 and dispersion corrected DFT methods. The red shift of the indole N-H stretch frequency in the dimer provides direct evidence that the experimentally observed indole-benzene dimer is an N-H···π bound hydrogen bonded complex. Theoretical investigations suggest that the potential energy surface (PES) of the complex is rather flat along the coordinate describing the tilt angle between the molecular planes of indole and benzene, with several minima of similar energies, namely, parallel displaced (PD), right-angle T-shaped (T), and other intermediate structures which can be categorized as tilted T-shaped (T') and tilted parallel displaced (PD') structures. Three different computational methods, namely, RI-MP2, RI-B97-D, and PBE1-DCP, are used to arrive at a new structural assignment after assessing their performance in predicting the structure of the pyrrole dimer, for which accurate experimental data are available. By comparing the computed IR spectra of PD, T, and T'/PD' structures with the experimental IR spectrum, the tilted T-shaped (T') structure was assigned to the indole-benzene dimer. The empirically dispersion-corrected functionals (RI-B97-D and PBE1-DCP) correctly reproduce the experimental IR spectrum whereas the popular post-Hartree-Fock, MP2 method gives disappointing results. These results are also in agreement with the experimental dissociation energy (D(0)) reported in the literature. The N-H stretch frequency of the indole-benzene dimer has been found to be a more pertinent parameter for the structural assignment than the dissociation energy (D(0)).

Tracing dynamic self-disassociation behavior of pyrrole with novel T-shaped hydrogen bonding

Near infrared spectroscopy (NIR) and two-dimensional correlation spectroscopy (2Dcos) were employed to study the dynamic self-disassociation behavior of hydrogen bonds in neat liquid pyrrole during heating. Two regions (7000-6430 cm(-1) for NH-related vibrational overtones and 6200-6100 cm(-1) for CH-related vibrational overtones and combination modes) are the focus of this paper, whose integral absorption temperature dependence exhibited a continuous convex variation. Two-dimensional correlation analysis has discerned the sequence of change of different aggregated species of pyrrole. Additionally, we carefully investigated the band shift phenomenon of N-H...pi hydrogen bonding in pyrrole dimers, and assigned this band shift as the result of the transformation of pyrrole dimers from T-shaped geometry to antiparallel geometry.

The structure and vibrational dynamics of the pyrrole dimer

The energy, dynamical geometry characteristics and low frequency intermolecular vibrations of the pyrrole dimer have been examined at the MP2 and CCSD(T) levels of ab initio theory. The actual distortions of the pyrrole dimer from its reference (equilibrium) position were measured using the distance of the monomer mass centres (R), the angle between their planes (the mirror planes orthogonal to the molecular planes of both monomers were assumed to coincide) and the angle between the R directional vector and the proton-accepting monomer plane; the structures of the monomers were assumed to be unchanged by dimerisation. The lowest part of the potential energy function confining the probed motions possessed two equivalent energy pockets with the CCSD(T)/complete basis set limit stabilisation energy of 6.2 kcal mol(-1) separated by a relatively low barrier (0.8 kcal mol(-1)), thus raising questions concerning the classical interconversion of the T-shaped equilibrium structures via a C(2h) parallel-displaced transient structure and/or quantum mechanical tunnellings through the barrier. The questions have been answered unequivocally by calculating the energies and tunnelling splittings of the relevant vibrational levels. Importantly: (a) all the excited tunnelling (interconverting) states underwent fast geometry interconversions, hence evidencing conformational instability of the studied dimer under usual laboratory conditions; (b) the dynamical averages of the used geometry characteristics exhibited profound tunnelling (interconverting) dependences, thus advocating that they be respected in reliable structural studies of the pyrrole dimer and chemically similar systems; (c) the geometry characteristics of the ground vibrational state agreed quite reasonably with their experimental counterparts, evidencing the adequacy of the theory used and the reliability of the characteristics predicted for the excited vibrational states; and (d) the calculated dissociation barrier of the dimer exceeds its experimentally derived analogue by more than three times, showing the inadequacy of the constraining assumptions used to derive it from the experimental spectra.

Chromogenic and Neurotoxic Effects of an Aliphatic γ-Diketone: Computational Insights into the Molecular Structures and Mechanism

First-principles electronic structure calculations have been performed to predict chromogenic properties of various candidate structures, including pyrrole monomers and dimers and their derivatives, of the chromophores formed from the reactions of 2,5-hexanedione (2,5-HD), a prototype of neurotoxic aliphatic γ-diketones, with NH3, amino acids, and proteins. The calculated results indicate that the pyrrole monomer structures and a previously proposed dimer structure do not have an absorption in the visible region (λ > ∼400 nm and < ∼700 nm), whereas a novel type of pyrrole dimer structure has absorptions (λ = ∼400 to 420 nm) in the visible region if the methyl (CH3) groups on the pyrrole rings are oxidized to CHO groups. The calculated results for the oxidized pyrrole dimer models for cross-linked proteins are consistent with all of the available experimental data for the chromogenic and neurotoxic effects of 2,5-HD. Our results strongly support the conclusion that the chromogenic effects of aliphatic γ-diketones are closely related to their neurotoxic effects and further predict that both the chromogenic and neurotoxic effects are associated with the same chemical reaction process. Such a reaction process most likely starts from the formation of the pyrrole−protein adducts followed by dimerization and further oxidization.

2-(2′-Pyridyl)pyrroles: Part II. Spectroscopic investigation of pyridylpyrrole alcohol complexes

A homologous series of 2-(2′-pyridyl)pyrroles were studied as a possible model system for intermolecular hydrogen bonding interactions in molecules that can act as both hydrogen bond donors and acceptors. Steady state spectroscopic methods were used to assess the importance of intermolecular hydrogen bonding interactions in dilute solutions of 2-(2′-pyridyl)pyrroles in the absence and presence of alcohols. The absorption and fluorescence properties of such solutions were investigated to determine the relevance of such hydrogen bonding interactions in the ground and excited state behavior of the 2-(2′-pyridyl)pyrroles. Over the concentration range studied, no evidence was found for the formation of hydrogen-bonded 2-(2′-pyridyl)pyrrole dimers. However, it was determined that 3,5-dimethyl-2-(2′-pyridyl)pyrrole forms weak (K ∼ 5–12 M−1) 1∶1 hydrogen-bonded complexes with methanol and t-butyl alcohol in the ground state, and 3,5-di-tert-butyl-2-(2′-pyridyl)pyrrole forms both 1∶1 and 1∶2 complexes with the same alcohols. Despite the formation of hydrogen-bonded 2-(2′-pyridyl)pyrrole alcohol complexes, no experimental evidence was found for excited state proton transfer in such complexes.