Π-stacking Interactions Research Articles

Shell-Isolated Nanoparticle-Enhanced Raman Spectroscopy for Probing Riboflavin on Graphene.

Graphene research and technology development requires to reveal adsorption processes and understand how the defects change the physicochemical properties of the graphene-based systems. In this study, shell-isolated nanoparticle-enhanced Raman spectroscopy (SHINERS) and graphene-enhanced Raman spectroscopy (GERS) coupled with density functional theory (DFT) modeling were applied for probing the structure of riboflavin adsorbed on single-layer graphene substrate grown on copper. Intense and detailed vibrational signatures of the adsorbed riboflavin were revealed by SHINERS method. Based on DFT modeling and detected downshift of prominent riboflavin band at 1349 cm−1 comparing with the solution Raman spectrum, π-stacking interaction between the adsorbate and graphene was confirmed. Different spectral patterns from graphene-riboflavin surface were revealed by SHINERS and GERS techniques. Contrary to GERS method, SHINERS spectra revealed not only ring stretching bands but also vibrational features associated with ribityl group of riboflavin and D-band of graphene. Based on DFT modeling it was suggested that activation of D-band took place due to riboflavin induced tilt and distortion of graphene plane. The ability to explore local perturbations by the SHINERS method was highlighted. We demonstrated that SHINERS spectroscopy has a great potential to probe adsorbed molecules at graphene.

A first-order phase transition in Blatter's radical at high pressure.

The crystal structure of Blatter's radical (1,3-diphenyl-1,4-dihydrobenzo[e][1,2,4]triazin-4-yl) has been investigated between ambient pressure and 6.07 GPa. The sample remains in a compressed form of the ambient-pressure phase up to 5.34 GPa, the largest direction of strain being parallel to the direction of π-stacking interactions. The bulk modulus is 7.4 (6) GPa, with a pressure derivative equal to 9.33 (11). As pressure increases, the phenyl groups attached to the N1 and C3 positions of the triazinyl moieties of neighbouring pairs of molecules approach each other, causing the former to begin to rotate between 3.42 to 5.34 GPa. The onset of this phenyl rotation may be interpreted as a second-order phase transition which introduces a new mode for accommodating pressure. It is premonitory to a first-order isosymmetric phase transition which occurs on increasing pressure from 5.34 to 5.54 GPa. Although the phase transition is driven by volume minimization, rather than relief of unfavourable contacts, it is accompanied by a sharp jump in the orientation of the rotation angle of the phenyl group. DFT calculations suggest that the adoption of a more planar conformation by the triazinyl moiety at the phase transition can be attributed to relief of intramolecular H...H contacts at the transition. Although no dimerization of the radicals occurs, the π-stacking interactions are compressed by 0.341 (3) Å between ambient pressure and 6.07 GPa.

Crystal structure and Hirshfeld surface analysis of 2-oxo-2-phenyl-ethyl 3-nitroso-2-phenyl-imidazo[1,2-a]pyridine-8-carboxyl-ate.

The title compound, C22H15N3O4, is built up from a central imidazo[1,2-a]pyridine ring system connected to a nitroso group, a phenyl ring and a 2-oxo-2-phenyl-ethyl acetate group. The imidazo[1,2-a] pyridine ring system is almost planar (r.m.s. deviation = 0.017 Å) and forms dihedral angles of 22.74 (5) and 45.37 (5)°, respectively, with the phenyl ring and the 2-oxo-2-phenyl-ethyl acetate group. In the crystal, the mol-ecules are linked into chains parallel to the b axis by C-H⋯O hydrogen bonds, generating R 2 1 (5) and R 4 4 (28) graph-set motifs. The chains are further linked into a three-dimensional network by C-H⋯π and π-stacking inter-actions. The inter-molecular inter-actions were investigated using Hirshfeld surface analysis and two-dimensional fingerprint plots, revealing that the most important contributions for the crystal packing are from H⋯H (36.2%), H⋯C/C⋯H (20.5%), H⋯O/O⋯H (20.0%), C⋯O/O⋯C (6.5%), C⋯N/N⋯C (6.2%), H⋯N/N⋯H (4.5%) and C⋯C (4.3%) inter-actions.

Molecular Basis of Small-Molecule Binding to α-Synuclein.

Intrinsically disordered proteins (IDPs) are implicated in many human diseases. They have generally not been amenable to conventional structure-based drug design, however, because their intrinsic conformational variability has precluded an atomic-level understanding of their binding to small molecules. Here we present long-time-scale, atomic-level molecular dynamics (MD) simulations of monomeric α-synuclein (an IDP whose aggregation is associated with Parkinson’s disease) binding the small-molecule drug fasudil in which the observed protein–ligand interactions were found to be in good agreement with previously reported NMR chemical shift data. In our simulations, fasudil, when bound, favored certain charge–charge and π-stacking interactions near the C terminus of α-synuclein but tended not to form these interactions simultaneously, rather breaking one of these interactions and forming another nearby (a mechanism we term dynamic shuttling). Further simulations with small molecules chosen to modify these interactions yielded binding affinities and key structural features of binding consistent with subsequent NMR experiments, suggesting the potential for MD-based strategies to facilitate the rational design of small molecules that bind with disordered proteins.

Merging antimicrobial and visible emission properties within 1,3,4-trisubstituted-1,2,3-triazolium salts.

Bioactive molecules displaying visible wavelength emission can be useful for bioimaging, chemosensing and photodynamic therapy applications. Reported herein are 1,3,4-trisubsituted-1,2,3-triazolium salts displaying both antimicrobial and visible emission properties. Using a click chemistry approach, 2-fluorenyl, 1-naphthyl, 2-naphthyl, 2-anthracenyl and 1-pyrenyl units were incorporated at the N1 position, imparting visible emission properties to their triazolium bromide salts with Stokes shifts greater than 100 nm relative to the emission of their triazole precursors. The increasing size of such hydrophobic aryl units impacts minimum inhibitory concentration (MIC) values against Gram-positive bacteria, Gram-negative bacteria and yeast, and can be counterbalanced by hydrophobic substituent variation at other positions of the molecule in order to preserve bioactivity. Among the series of compounds studied are analogs displaying blue, green and yellow colored emission and MIC values as low as 0.4 μM (Gram-positive bacteria), 8 μM (Gram-negative bacteria) and 2 μM (yeast). XRD analysis validates the regioselective benzylation at the N3 position of the 1,2,3-triazole ring and the ability of such compounds to associate through dimeric intermolecular π-stacking interactions.

A Sulfonated Tweezer-Shaped Receptor Selectively Recognizes Caffeine in Water.

The selective recognition of caffeine in water among structurally related xanthines and purine or pyrimidine bases was achieved by a simple tweezer-shaped receptor featuring sulfonate hydrosolubilizing groups. The remarkable affinity for caffeine, among the highest reported thus far in the literature and larger than that shown by adenosine receptors of all subtypes, stems from a synergistic combination of hydrogen bonding, CH−π, and π-stacking interactions.

Bis[3-(anthracen-9-yl)pentane-2,4-dionato-κ2 O,O'](N,N-di-methyl-formamide-κO)[tris-(pyrazol-1-yl-κN 2)hydroborato]europium(III).

The title compound, [Eu(C9H10BN6)(C19H15O2)2(C3H7NO)] or [TpEu(Anthracac)2(DMF)], was synthesized by reaction of a tris-(pyrazol-yl)borate (Tp-) Eu3+ complex with 3-(anthracen-9-yl)pentane-2,4-dione (HAnthracac) in the presence of tri-ethyl-amine. In the title compound, Eu3+ is located in an octa-vertex square-pyramidal coordination environment. In the two Anthracac- ligands, the anthracene and nearly planar acetyl-acetonate fragments are almost orthogonal. Neighboring mol-ecules of TpEu(Anthracac)2(DMF) are connected in the crystal by inter-molecular van der Waals inter-actions, while π-stacking inter-actions are limited to the edges of two anthracene rings.

Unraveling the Role of π-Stacking Interactions in Ligand Binding to the Thiamine Pyrophosphate Riboswitch with High-level Quantum Chemical Calculations and Docking Study.

The thiamine pyrophosphate (TPP) riboswitch has emerged as the new target for designing new ligands for antibiotic purpose. Binding of the natural ligand TPP to the TPP riboswitch causes downregulation of the genes responsible for its biosynthesis. We have reported the role of π-stacking energy contributions to ligand binding with a TPP riboswitch. In conjunction with the docking study, the higher-level quantum chemical calculations performed with the wB97XD and Def2TZVPP basis set in the aqueous phase revealed that the optimum ring size is crucial to attain the effective binding efficiency of ligands with a TPP riboswitch. The π-stacking energy contributions observed for the ligands studied are largely similar; however, the cases studied with higher π-stacking energies with larger rings have a weaker ability to displace the radiolabeled thiamine from the riboswitch. The EDA and NCI analyses suggest the role of larger dispersive interactions in stabilizing the π-stacking rings. The contribution from hydrogen-bonding interactions of the hydrogen-bond donor groups on the A ring augments the binding affinity of the ligand. This study sheds light on various factors that contribute to the design of new ligands for efficient binding with a TPP riboswitch and inhibition of gene expression.

Guanine-Based G-Quadruplexes Templated by Various Cations toward Potential Use as Single-Ion Conductors.

Inspired by the atomic-sized, shape-regulated features of G-quadruplexes comprising guanine motifs with a monovalent metal cation, the G-quadruplex-forming ability, and properties of a guanine-based π-conjugated Y2 molecule containing bithiophene and peripheral dodecyl chain units in the presence of various cation salts (Li+ , Na+ , K+ , and Mg2+ ) were exploited. A series of structural characterization revealed that Y2 yielded desirable G-quadruplexes with all the tested cations as a consequence of the combination of a hydrogen-bonded cyclic G-quartet, π-stacking, and cation-dipole interactions. The radius and nature of the coordinating cations crucially affected the structural characteristics of G-quadruplexes, leading to variations in the ion migration ability inside the cavity of the G-quadruplex (Li+ >Na+ >K+ >Mg2+ ), as characterized through theoretical and experimental investigations. These results not only improve the understanding of G-quadruplex self-assemblies based on guanine but also provide an impetus for their diverse potential applications, especially in the field of Li batteries.

Contributions of Conformational Flexibility to High-Affinity Zinc Binding in the Solute Binding Protein AztC.

Bacteria rely on ATP binding cassette (ABC) transporters for the import of various nutrients. Bacterial ABC importers utilize an extracellular solute binding protein (SBP) to bind the substrate with high affinity and specificity and deliver it to the membrane permease for transport. The essential metals iron, manganese, and zinc are bound and transported by the cluster A–I SBPs. Crystal structures exist for the metal-bound and metal-free forms of several cluster A–I SBPs that show relatively subtle conformational changes that accompany metal binding. Recent solution studies and molecular dynamics simulations indicate a more complex conformational landscape for the cluster A–I SBPs, suggesting that changes in protein dynamics upon metal binding may have an important role in recognition by the membrane permease and effective transport. Here, we investigate conformational states and dynamics in the cluster A–I SBP AztC fromParacoccus denitrificans, characterizing its unusual intrinsic fluorescence behavior and thermodynamics of zinc binding. These data suggest a dynamic equilibrium of at least two conformational states in the apo form and compensatory changes in the holo that provide for a significant entropic contribution to zinc binding. Correlation with available crystal structures suggests that the formation of a Trp–Phe π-stacking interaction in the metal-bound form may mediate the observed changes in fluorescence. The conformational dynamics identified here for AztC are likely applicable to other cluster A–I SBPs with relevance to their exploitation as potential antibiotic drug targets.

Programmed Macromolecular Assembly by Dipole-Dipole Interactions with Aggregation-Induced Enhanced Emission in Aqueous Medium.

Self-assembling polymers by bioinspired directional supramolecular interactions currently hold great scientific and technological interests. Herein, we report an unorthodox strategy based on a dipole-dipole interaction-mediated extended antiparallel dipolar assembly of a model merocyanine (MC) dye for maneuvering the self-assembly of a highly water-soluble MC-functionalized block copolymer (P2). Unlike traditional amphiphilic block copolymers featuring distinct hydrophobic segments (flexible aliphatic hydrocarbon chains or rigid nonpolar aromatic scaffolds), P2 comprises polyethylene glycol monomethyl ether (PEG) as a hydrophilic block and an unconventional structure-directing acrylate block functionalized with polar MC-dyes in the side chains of every repeat unit. In the absence of any additional hydrophobic assistance, P2 spontaneously self-assembles in water through the continuous opposite alignment of its pendant MCs by multiple dipole-dipole interactions to cancel out their ground state dipole moments, which initially generates an H-aggregated species with ill-defined morphology (Aggregate 1). Upon thermal annealing, Aggregate 1 reorganizes into higher-order core-shell nanodisc-like structures (Aggregate 2) driven by the orthogonal π-stacking interactions of the rigid aromatic framework derived from the extended cofacial MC-stacks. The aromatic interiors of the nanodiscs gain colloidal stability from the externally decorated hydrophilic PEG chains. While the initially formed Aggregate 1, predominantly by dipole-dipole interactions, showed remarkable thermal stability due to the cooperative effect of the polymer chain, the hierarchical assembly guided by relatively weaker dispersion forces of the MC-stacked π-surfaces could be tailored by dilution or thermal treatment. Such organized packing of pendant MCs by the dual effect of dipole-dipole interactions and π-stacking conferred several exciting properties to the P2 assembly in water. Long-range ordered antiparallel stacking of the pendant MCs rendered outstanding aggregation-induced enhanced emission (AIEE) properties to the resultant nanostructures in water with increased fluorescence lifetime, quantum yield, and Stokes shift compared to nonaggregating P2 in CHCl3. The remarkable thermal and kinetic stability of the nanodiscs, their guest loading ability, and very low critical aggregation concentration (CAC) were demonstrated by Förster resonance energy transfer (FRET) studies with an encapsulated donor-acceptor dye pair.

Novel Macrocyclic Peptidomimetics Targeting the Polo-Box Domain of Polo-Like Kinase 1.

The polo-box domain (PBD) of Plk1 is a promising target for cancer therapeutics. We designed and synthesized novel phosphorylated macrocyclic peptidomimetics targeting PBD based on acyclic phosphopeptide PMQSpTPL. The inhibitory activities of 16e on Plk1-PBD is >30-fold higher than those of PMQSpTPL. Both 16a and 16e possess excellent selectivity for Plk1-PBD over Plk2/3-PBD. Analysis of the cocrystal structure of Plk1-PBD in complex with 16a reveals that the 3-(trifluoromethyl)benzoyl group in 16a interacts with Arg516 through a π-stacking interaction. This π-stacking interaction, which has not been reported previously, provides insight into the design of novel and potent Plk1-PBD inhibitors. Furthermore, 16h, a PEGlyated macrocyclic phosphopeptide derivative, induces Plk1 delocalization and mitotic failure in HeLa cells. Also, the number of phospho-H3-positive cells in a zebrafish embryo increases in proportion to the amount of 16a. Collectively, the novel macrocyclic peptidomimetics should serve as valuable templates for the design of potent and novel Plk1-PBD inhibitors.

Tuning Exciton Coupling of Merocyanine Nucleoside Dimers by RNA, DNA and GNA Double Helix Conformations.

Exciton coupling between two or more chromophores in a specific environment is a key mechanism associated with color tuning and modulation of absorption energies. This concept is well exemplified by natural photosynthetic proteins, and can also be achieved in synthetic nucleic acid nanostructures. Here we report the coupling of barbituric acid merocyanine (BAM) nucleoside analogues and show that exciton coupling can be tuned by the double helix conformation. BAM is a nucleobase mimic that was incorporated in the phosphodiester backbone of RNA, DNA and GNA oligonucleotides. Duplexes with different backbone constitutions and geometries afforded different mutual dye arrangements, leading to distinct optical signatures due to competing modes of chromophore organization via electrostatic, dipolar, π–π‐stacking and hydrogen‐bonding interactions. The realized supramolecular motifs include hydrogen‐bonded BAM–adenine base pairs and antiparallel as well as rotationally stacked BAM dimer aggregates with distinct absorption, CD and fluorescence properties.

Augmented Self-Association by Electrostatic Forces in Thienopyrrole-Fused Thiadiazoles that Contain an Ester instead of an Ether Linker.

During the self-assembly of π-conjugated molecules, linkers and substituents can potentially add supportive noncovalent intermolecular interactions to π-stacking interactions. Here, we report the self-assembly behavior of thienopyrrole-fused thiadiazole (TPT) fluorescent dyes that possess ester or ether linkers and dodecyloxy side chains in solution and the condensed phase. A comparison of the self-association behavior of the ester- and ether-bridged compounds in solution using detailed UV-vis, fluorescence, and NMR spectroscopic studies revealed that the subtle replacement of the ether linkers by ester linkers leads to a distinct increase in the association constant (ca. 3-4 fold) and the enthalpic contribution (ca. 3 kcal mol-1 ). Theoretical calculations suggest that the ester linkers, which are in close proximity to one another due to the π-stacking interactions, induce attractive electrostatic forces and augment self-association. The self-assembly of TPT dyes into well-defined 1D clusters with high aspect ratios was observed, and their morphologies and crystallinity were investigated using SEM and X-ray diffraction analyses. TPTs with ester linkers exhibit a columnar liquid crystalline mesophase in the condensed phase.

TADF: Enabling luminescent copper(i) coordination compounds for light-emitting electrochemical cells.

The last decade has seen a surge of interest in the emissive behaviour of copper(i) coordination compounds, both neutral compounds that may have applications in organic light-emitting doides (OLEDs) and copper-based ionic transition metal complexes (Cu-iTMCs) with potential use in light-emitting electrochemical cells (LECs). One of the most exciting features of copper(i) coordination compounds is their possibility to exhibit thermally activated delayed fluorescence (TADF) in which the energy separation of the excited singlet (S1) and excited triplet (T1) states is very small, permitting intersystem crossing (ISC) and reverse intersystem crossing (RISC) to occur at room temperature without the requirement for the large spin–orbit coupling inferred by the presence of a heavy metal such as iridium. In this review, we focus mainly in Cu-iTMCs, and illustrate how the field of luminescent compounds and those exhibiting TADF has developed. Copper(i) coordination compounds that class as Cu-iTMCs include those containing four-coordinate [Cu(P^P)(N^N)]+ (P^P = large-bite angle bisphosphane, and N^N is typically a diimine), [Cu(P)2(N^N)]+ (P = monodentate phosphane ligand), [Cu(P)(tripodal-N3)]+, [Cu(P)(N^N)(N)]+ (N = monodentate N-donor ligand), [Cu(P^P)(N^S)]+ (N^S = chelating N,S-donor ligand), [Cu(P^P)(P^S)]+ (P^S = chelating P,S-donor ligand), [Cu(P^P)(NHC)]+ (NHC = N-heterocyclic carbene) coordination domains, dinuclear complexes with P^P and N^N ligands, three-coordinate [Cu(N^N)(NHC)]+ and two-coordinate [Cu(N)(NHC)]+ complexes. We pay particular attention to solid-state structural features, e.g. π-stacking interactions and other inter-ligand interactions, which may impact on photoluminescence quantum yields. Where emissive Cu-iTMCs have been tested in LECs, we detail the device architectures, and this emphasizes differences which make it difficult to compare LEC performances from different investigations.

Static discrete disorder in the crystal structure of iododiflunisal: on the importance of hydrogen bond, halogen bond and π-stacking interactions

We report a combined computational/crystallographic analysis focused on the static discrete disorder shown by the drug iododiflunisal.

Unveiling the role of pyrylium frameworks on π-stacking interactions: a combined ab initio and experimental study.

A multidisciplinary study is presented to shed light on how pyrylium frameworks, as π-hole donors, establish π-π interactions. The combination of CSD analysis, computational modelling (ab intitio, DFT and MD simulations) and experimental NMR spectroscopy data provides essential information on the key parameters that characterize these intereactions, opening new avenues for further applications of this versatile heterocycle.

On the importance of π-stacking interactions in the complexes of copper and zinc bearing pyridine-2,6-dicarboxylic acid N-oxide and N-donor auxiliary ligands

Using N- and O-donor ligands in a mixed-ligand system, three new coordination complexes have been X-ray characterized, exhibiting strong π–π stacking interactions.

Metallophilic interactions in silver(I) dicyanoaurate complexes.

This manuscript reports four new gold(I)-silver(I) complexes with 2-(2-pyridyl)-1,8-naphthyridine (pyNP) and terpyridine (terpy) as ancillary ligands, having formulae [Ag(pyNP)(Au(CN)2)]2 (1), [Ag2Au2(μ-CN)2(CN)2(pyNP)2] (2), [Ag2Au(μ-CN)2(terpy)2][Au(CN)2] (3) and [Ag4Au4(μ-CN)8(terpy)2(py)] (4). Complexes 1 and 2 are structural isomers obtained from different solvents. The Au(CN)2- anion is not coordinated and establishes intramolecular Au⋯Ag,Ag interactions in 1. In contrast, it is monocoordinated to silver atoms via a CN fragment in compound 2 and no metallophilic interaction is observed. In compound 3, one Au(CN)2 anion bridges two Ag(terpy) fragments. In this complex an infinite array of gold atoms is found, exhibiting aurophilic interactions of 3.415 Å. In complex 4 the 3D architecture observed in the crystal packing is driven by Au⋯Au and Au⋯Ag metallophilic interactions. All compounds have been structurally and vibrationally characterized to better understand the crystal forces. In addition, a solution chemistry study in different solvents by ESI-MS spectrometry was performed to comprehend the speciation and solvent effects. Finally, DFT calculations were carried out to analyze the Ag⋯Au interactions and also the π-stacking interactions that are relevant in the crystal packing of some structures. Special attention has been paid to the bifurcated nature of the Au⋯Ag,Ag interactions in compound 1 that has been analyzed theoretically using the quantum theory of atoms-in-molecules (QTAIM) and the Natural Bond Orbital (NBO) computational tools.

1-(2,6-dimethylphenyl)-5-allylsulfanyl-1H-tetrazole and its copper(I) tetrafluoroborate n,σ-complex: synthesis, structure and quantum-chemical calculations

1-(2,6-Dimethylphenyl)-5-allylsulfanyl-1 H -tetrazole ( o-dmphast ) and its copper(I) tetrafluoroborate p,σ-complex [Cu 2 ( o-dmphast ) 2 (BF 4 ) 2 ] ( 1 ) were synthesized and X-ray structurally studied. o-Dmphast was prepared in several stages by known protocol, starting from 2,6-dimethyl aniline. The single crystals of 1 were obtained by means of the alternating-current electrochemical technique. The collected diffraction data were processed using CrysAlis RED program. The structures were solved by ShelXT program and refined by least squares method on F 2 by ShelXL program with the following graphical user interface of OLEX 2 . Compound 1 crystallizes in the centrosymmetric space group : a = 7.405(3)), b = 7.786(3), c = 11.625(4) Å, a = 101.90(3) , β = 100.88(3) , g = 104.81(3) , V = 613.0(4) Å 3 , Z = 2. π-Complexe crystallizes in the centrosymmetric space group P 2 1 /n .: a = 9.271(3), b = 14.171(4), c = 11.956(4) Å, β = 91.52(3) , V = 1570.2(9) Å 3 , Z = 2. Allylsulfanyl group of o-dmphast has synclinal conformation relative to the S1—C3 bond and antisynclinal conformation relative to the C2—C3 bond (the corresponding torsion angles C5—S1—C3—C2 and S1—C3—C2—C1 are 76.5(2) and –118.0(3)). In the structure of o-dmphast , the hydrogen atom of the one methyl group (C13) and the hydrogen atom of the methylene group of the allyl substituent form weak С−H···N hydrogen bonds with the nitrogen atoms of the tetrazole ring of neighboring molecules. Tetrazole rings of the nearest molecules are involved in the π···π-stacking interaction at a distance of 3.44 Å. Structure of 1 is built of centrosymmetric dimers which are formed by coordination to two Cu + ions of two chelate-bridging molecules o-dmphast . The dimeric moieties contain a six-membered {Cu 2 N 4 } ring comprised of two pairs of [ - N - N - ] tetrazole fragments. π-Coordinated Cu(I) cation adopts a close to a trigonal pyramidal coordination environment (2N, (C=C) + F). The corresponding four-coordinate geometry indexes τ 4 is 0.78. Copper(I) ion and allylic group (C1, C2 and С3 atoms) in 1 are disordered over two sites with an occupancy ratio of 0.522(4):0.478(4). Fluorine atoms of the anion are also disordered over two sites with an occupancy ratio of 0.737(3):0.263(3). To further analyse the intermolecular interactions in the structures of o-dmphast , Hirshfeld surface analysis and energy framework computational analysis have been performed. Keywords: copper(I), π-complex, allyl derivative of tetrazole, crystal structure, quantum-chemical calculations.