Halogen-bonding Interactions Research Articles

Design and structural characterization of 2-methyl 8-hydroxyl quinolinilium 5-chloro salicylate salt

The enhanced physico chemical properties of 2-methyl 8-hydroxy quinolone was observed by the modified 2-methyl 8-hydroxy quinolinium 5-chloro salicylate crystal structure which were grown by slow evaporation method. The crystal structure was confirmed by single X-ray diffraction analysis. Crystal structure was stabilized through halogen bond interaction in the title crystal. The 3D Hirshfeld surfaces and the associated 2D fingerprint plots were investigated for intermolecular hydrogen bonding interactions. FTIR and FT-Raman spectral studies were characterized to reveal the presence of functional groups in the grown crystal. The proton and carbon chemical shift of the title compound were observed by 1H and 13C NMR analysis. Excited energy of the title compound was observed using UV-Visible spectral analysis. The fluorescence solid and solvent spectrum revealed that the green emission was observed in the grown crystal. The melting behavior and stability of the title compound was performed by TGA-DSC analysis. The ability to show the pharmacological behavior of the title crystal was analyzed by anti-oxidant, anti-microbial and anti-cancer studies.

Crystal Engineering of Binary Organic Eutectics: Significant Improvement in the Physicochemical Properties of Polycyclic Aromatic Hydrocarbons via the Computational and Mechanochemical Discovery of Composite Materials

Derivatives of polycyclic aromatic hydrocarbons (PAHs) are widely used in optoelectronic materials. However, the poor solubility of unfunctionalized PAHs represents a challenge for the continued application of these compounds in emerging technologies. For organic compounds bearing one or more functional groups capable of engaging in directional hydrogen or halogen-bonding interactions, the crystal engineering toolkit currently offers many routes for optimizing the solid-state properties of these compounds. Such efforts typically lead to the discovery of periodic crystal forms that display strong adhesive intermolecular forces between the molecular fragments. By contrast, the crystal engineering of organic eutectic composites is relatively unexplored and poorly understood. Here, we report the mechanosynthesis and experimental characterization of the properties of three eutectic composites of pyrene (PYR) and anthracene (ANTH) that were discovered using the coformer bisphenol A (BPA) or phenothiazine (PTZ). The resulting eutectic composites (PYR-BPA, PYR-PTZ, and ANTH-PTZ) display significant melting point depressions ranging from 19 to 51 °C relative to the melting point of the PAH. The equilibrium solubilities of the composite materials were also observed to be 2–5 times greater than that of the PAH. The crystal engineering of eutectic solid forms is currently hampered by the lack of reliable empirical or theoretical tools for predicting their formation. A weighted Monte Carlo simulation was used to estimate the mixing energies and binding modes of a limited set of molecular pairs, leading to temperature-dependent interaction parameters that show promise in the selection of coformers with a high likelihood of forming eutectic composites. Complementary dispersion-corrected density functional theory (DFT-D) calculations on a set of PYR and ANTH composite models reveal that organic eutectic composites are not driven to form on the basis of favorable thermodynamics as evidenced by an average interaction energy of 2.60 kJ mol–1 across the series. Synthon incompatibility and molecular shape mismatch appear to be important factors to consider in targeting eutectic solid forms. This work paves the way for the systematic crystal engineering of organic eutectic solid forms with tunable physicochemical properties using a synergistic computational modeling and mechanosynthesis approach.

Tuning the activity of known drugs via the introduction of halogen atoms, a case study of SERT ligands - Fluoxetine and fluvoxamine.

The selective serotonin reuptake inhibitors (SSRIs), acting at the serotonin transporter (SERT), are one of the most widely prescribed antidepressant medications. All five approved SSRIs possess either fluorine or chlorine atoms, and there is a limited number of reports describing their analogs with heavier halogens, i.e., bromine and iodine. To elucidate the role of halogen atoms in the binding of SSRIs to SERT, we designed a series of 22 fluoxetine and fluvoxamine analogs substituted with fluorine, chlorine, bromine, and iodine atoms, differently arranged on the phenyl ring. The obtained biological activity data, supported by a thorough in silico binding mode analysis, allowed the identification of two partners for halogen bond interactions: the backbone carbonyl oxygen atoms of E493 and T497. Additionally, compounds with heavier halogen atoms were found to bind with the SERT via a distinctly different binding mode, a result not presented elsewhere. The subsequent analysis of the prepared XSAR sets showed that E493 and T497 participated in the largest number of formed halogen bonds. The XSAR library analysis led to the synthesis of two of the most active compounds (3,4-diCl-fluoxetine 42, SERT Ki=5nM and 3,4-diCl-fluvoxamine 46, SERT Ki=9nM, fluoxetine SERT Ki=31nM, fluvoxamine SERT Ki=458nM). We present an example of the successful use of a rational methodology to analyze binding and design more active compounds by halogen atom introduction. 'XSAR library analysis', a new tool in medicinal chemistry, was instrumental in identifying optimal halogen atom substitution.

Exploring influence of fluorine substitution on the strength and nature of halogen bond between iodobenzene and hydrogen cyanide

AbstractIn the present study, the intermolecular I … N halogen bond (XB) interaction between iodobenzene (IBZ) and its fluorinated derivatives (as Lewis acids LA 1 through LA 20) with HCN (as Lewis base LB) is theoretically explored to shed light on the electronic nature and strength of the mentioned non‐covalent interaction (NCI). The hydrogen atoms of phenyl ring in IBZ were substituted by fluorine atom to probe different impacts of this atom. Such a substitution is paid attention from the number as well as the position of fluorine atoms points of view. Our analyses reveal that this XB interaction whose interaction energy spans a narrow range between 1.0 and 3.0 kcal·mol−1should be classified as a weak NCI. The symmetry‐adapted perturbation theory (SAPT) analysis evidences that the I … N XB in the investigated binary complexes (BCs) is mainly dominated by electrostatic and dispersion interactions, and, in the meantime, induction interactions can safely be ignored. Among the many I … N XB descriptors,Vs,max, which corresponds to the most positive value of electrostatic potential computed for the iodine atom in LAs, plays a key role. Indeed, such an easily and rapidly computable quantity (Vs,max) allows a sufficiently accurate prediction of interaction energy together with SAPT‐derived components analysis to become feasible by a simple inclusion ofVs,maxvalue within the numerous explored estimators. Although the strength of I … N XB interaction in the studied BCs is increased by an increase in the number of fluorine substituent, the position of fluorine atom cannot significantly alter the strength of the mentioned interaction.

Quaternary Cocrystals Based on Halide-Binding Foldamers through Both Hydrogen and Halogen Bonding

A series of quaternary cocrystals (R4N)2[L(X)2]·Sol (1–6) have been obtained through a combination of halogen bond (XB) and hydrogen bond (HB) interactions between a dihalide foldamer (formed by a ...

Halogen bond interaction: Role of hybridization and induction

Selected systems bearing carbon-chlorine (CCl) bond and their complexes with two representative Lewis bases have been examined by means of quantum-chemistry DFT calculations to gain a deeper insight into the parameters affecting the halogen bond (XB) interaction. The dependence of the C hybridization (sp, sp2, sp3) and induction (by replacing the H atoms with the F electron-withdrawing atoms) on the polar flattening (PF), the σ-hole and the charge transfer (CT) in the XB complex has been unraveled.

Anions effect construction of 1D naphthalene diimide supramolecular chains by π interactions and fluorescence detect iodide anion

Five diverse 1D supramolecular chains, {[4-pmntd]}n(1), {H2[4-pmntd]•2Br−}n(2), {H2[4-pmntd]•2NO3−}n(3), {H2[4-pmntd]•2ClO4−}n(4), {H2[4-pmntd]•2BF4−}n(5), (where 4-pmntd was N,N′-bis (4-pyridylmethyl)naphthalene diimide) were synthesized and characterized by X-ray single-crystal structure analysis, IR spectroscopy, elemental analyses, thermogravimetric analyses, fluorescence detection. The anions effect construction of their 1D chain structural diversity through different π interactions. Compound 1 through the adjacent pyridine rings parallel π∙∙∙π interactions formed 1D linear chain structure. Compound 2 through Br− anion∙∙∙π interactions and halogenbond interactions formed 1D zigzag chain structure. Compound 3 through lone pair∙∙∙π interactions of naphthalene diimide and the adjacent carboxyl group formed 1D stairway chain structure. Compound 4 through ClO4− anion∙∙∙π interactions formed 1D ribbon chain structure. Compound 5 through parallel π∙∙∙π interactions of the adjacent naphthalene diimide planes and pyridine rings formed 1D ladder chain structure. The five compounds’ fluorescence properties and thermal stabilities were investigated. The compound 2 solution could fluorescence detection for iodide anion via fluorescence quenching.

In silico characterization and prediction of thiourea-like neutral bidentate halogen bond catalysts.

Preorganization is a common strategy to align halogen bond (XB) donors to form two or more halogen bonds simultaneously. Previous approaches have utilized various non-covalent interactions such as steric interactions, ππ stacking, and hydrogen bond interactions. However, some of the introduced aligning interactions may compete with halogen bond interactions if the donors are employed in catalysis. To achieve thiourea-like properties, we have designed in silico several neutral bidentate halogen bond donors in whose structures the donor moieties are connected via covalent bonds. Compared to previous XB catalyst designs, the new design does not involve other potentially competitive non-covalent interactions such as hydrogen bonds. One of the designed XB donors can deliver strong halogen bonds, with a O-I distance as short as 2.64 Å. Density functional theory (DFT) calculations predicted that our designed catalysts may catalyze important organic reactions on their own, particularly for those reactions that involve (developing) soft anions such as thiolates.

Recent Topics in Organohalogen Reagents and Compounds

This Special Issue covers the hot topics on recent synthetic interest in halogen and related chemistry as well as the unique characteristics of halogen compounds. The excellent reviews by the experts and eminent researchers engaged in the recent advances, i.e., preparations, reactions, and mechanistic studies of unique organohalogen compounds, halogen bond interaction as the catalysis, and halogen-controlled unique reactions for synthesizing useful organic molecules, such as pharmaceutical compounds and organic materials, are provided in this Special Issue.

Recent Advances in Halogen Bond-assisted Organic Synthesis

Halogen bond interactions, which take place between an electrophilic halogen and the electron-pair of a Lewis base and exhibit high directionality (approximately 180°), are non-covalent bond interactions similar to the hydrogen bond interaction. Many reports on halogen bond interactions have been published thus far, but many of them discuss halogen bond in the context of crystal engineering of supramolecular architecture. Since a seminal report by Bolm in 2008, halogen bond-assisted or -promoted organic synthesis has received significant attention. This review aims to introduce the molecular design of suitable halogen bond donors and organic transformations involving halogen bond interactions to afford a variety of organic compounds.

Study on the halogen bond and π-π stacking interaction between fluoro substituted iodobenzene and pyrazine

The halogen bonding and π-π stacking interactions between pyrazine (C4H4N2) and fluoro substituted iodobenzene C6H5-nFnI (n = 0, 1, 2, 3, 4, and 5) have been discussed at the M062x-D3/aug-cc-pVTZ level. The calculated interaction energy shows that the halogen bonding interactions are weaker than the corresponding π-π stacking interactions in C6H5-nFnI (n = 0, 1, and 2)-C4H4N2 complexes, while the halogen bonding interactions are stronger than the corresponding π-π stacking interactions in C6H5-nFnI (n = 3, 4, and 5)-C4H4N2 complexes. According to SAPT analysis, it is reveals that the electrostatic energy are the primary source of the attraction for the halogen bonding interactions while the π-π stacking interactions are dominantly dispersion energy. When the halogen bond and π-π stacking interaction coexist, we find out that the formation of π-π stacking will lead to stronger halogen bond interaction and the converse is also true. Graphical abstract.

Halogen bonds and other noncovalent interactions in the crystal structures of trans-1,2-diiodo alkenes: an ab initio and QTAIM study.

A series of interatomic interactions interpretable as halogen bonds involving I…I, I…O, and I…C(π), as well as the noncovalent interactions I…H and O…O, were observed in the crystal structures of trans-1,2-diiodoolefins dimers according to ab initio calculations and the quantum theory of "atoms in molecules" (QTAIM) method. The interplay between each type of halogen bond and other noncovalent interactions was studied systematically in terms of bond length, electrostatic potential, and interaction energy, which are calculated via ab initio methods at the B3LYP-D3/6-311++G(d,p) and B3LYP-D3/def2-TZVP levels of theory. Characteristics and nature of the halogen bonds and other noncovalent interactions, including the topological properties of the electron density, the charge transfer, and their strengthening or weakening, were analyzed by means of both QTAIM and "natural bond order" (NBO). These computational methods provide additional insight into observed intermolecular interactions and are utilized to explain the differences seen in the crystal structures. Graphical abstract The contour map presents the regions of electronic concentration and depletion along each bond in one dimer. The blue points denote the BCPs. The blue lines denote positive Laplacian of electron density, which indicate the ionic interactions, van der Waals or intermolecular interactions, and the red lines denote negative Laplacian of electron density which indicate the covalent bonds.

Theoretical rationale for the role of the strong halogen bond in the design and synthesis of organic semiconductor materials

The 1,8-naphthyridine and diiodine were selected as model molecules to investigate the possible effect of the strong N⋯I halogen bond on the electronic structures and properties of potential organic semiconductor building blocks. The N⋯I halogen bond in the crystal structure of the cocrystal formed between 1,8-naphthyridine and diiodine has an interaction energy of −21.41 kcal/mol. The cooperativity and anticooperativity between the strong halogen bond and other noncovalent interactions, including the hydrogen bond, tetrel bond and stacking interaction, were also studied in detail. The formation of the strong N⋯I halogen bond leads to the formation of the regularly layered structures of the cocrystal, which is a necessary condition for the organic semiconductor to conduct electrons or holes. On the other hand, the formation of the strong N⋯I halogen bond lowers both the energy of the lowest unoccupied molecular orbital of 1,8-naphthyridine and the energy gap of frontier molecular orbitals of 1,8-naphthyridine. These results clearly show that the strong halogen bond can be used as a cheap and effective tool for the design and synthesis of organic semiconductor materials.

Strong σ-Hole Activation on Icosahedral Carborane Derivatives for a Directional Halide Recognition.

Crystal engineering based on σ-hole interactions is an emerging approach for realization of new materials with higher complexity. Neutral inorganic clusters derived from 1,2-dicarba-closo-dodecaborane, substituted with -SeMe, -TeMe, and -I moieties on both skeletal carbon vertices are experimentally demonstrated herein as outstanding chalcogen- and halogen-bond donors. In particular, these new molecules strongly interact with halide anions in the solid-state. The halide ions are coordinated by one or two donor groups (μ1 - and μ2 -coordinations), to stabilize a discrete monomer or dimer motifs to 1D supramolecular zig-zag chains. Crucially, the observed chalcogen bond and halogen bond interactions feature remarkably short distances and high directionality. Electrostatic potential calculations further demonstrate the efficiency of the carborane derivatives, with Vs,max being similar or even superior to that of reference organic halogen-bond donors, such as iodopentafluorobenzene.

Strongσ‐Hole Activation on Icosahedral Carborane Derivatives for a Directional Halide Recognition

AbstractCrystal engineering based onσ‐hole interactions is an emerging approach for realization of new materials with higher complexity. Neutral inorganic clusters derived from 1,2‐dicarba‐closo‐dodecaborane, substituted with ‐SeMe, ‐TeMe, and ‐I moieties on both skeletal carbon vertices are experimentally demonstrated herein as outstanding chalcogen‐ and halogen‐bond donors. In particular, these new molecules strongly interact with halide anions in the solid‐state. The halide ions are coordinated by one or two donor groups (μ1‐ and μ2‐coordinations), to stabilize a discrete monomer or dimer motifs to 1D supramolecular zig‐zag chains. Crucially, the observed chalcogen bond and halogen bond interactions feature remarkably short distances and high directionality. Electrostatic potential calculations further demonstrate the efficiency of the carborane derivatives, withVs,maxbeing similar or even superior to that of reference organic halogen‐bond donors, such as iodopentafluorobenzene.

Insight into the halogen-bonding interactions in the C6F5X···ZH3 (X = Cl, Br, I; Z = N, P, As) and C6F5I···Z (Ph)3 (Z = N, P, As) complexes

The ability of C6F5X (X = Cl, Br, I) to favorably interact with ZH3 (Z = N, P, As) was evaluated at the level of M06-2X functional. For comparison, the C6F5I···ZPh3 (Z = N, P, As) complex was also studied. The halogen bond donors C6F5X (X = Cl, Br, I) have positive regions of electrostatic potentials (ESP) outside the X atom, and could interact with the negative ESP outside the Z atom of ZH3 (Z = N, P, As) to form the X···Z halogen bond. When the halogen bond donor remains unchanged, the halogen bond strength grows along the decreasing size of As, P, and N. When halogen bond acceptor remains unchanged, the halogen bond becomes stronger gradually along the sequence of X = Cl, Br, I. It was found that C6F5I···ZPh3 complex greatly reduces the strength of the halogen bond comparing with the C6F5I···ZH3.

High sensitive pyridine chemiresistive sensors based on azacyclobutane modified perylene bisimide derivatives

A novel bay brominated perylene bisimide derivative with azacyclobutane modified (PBI–1N) was designed and synthesized. The derivative had good solubility in organic solvents and excellent self-assembly properties.The networked structure of PBI-1N was transferred to the surface of the device to prepare the chemiresistive sensor, and its sensing performance was studied. There is a higher sensitivity for PBI-1N-based sensor with experimental detection limit of pyridine reaching 375 ppb. Moreover, the pyridine and its derivatives can be distinguished by introducing halogen bond interaction. This provides a useful reference for the molecular structure design of high performance organic semiconductors in the future.

Utilizing Co-Crystallization as a Tool to Unravel the Structural Diversity and Electronic Features of I···S Halogen Bonded Interactions in Stoichiomorphic Co-Crystals

In the current investigation, we report five new co-crystals formed by combinations of triphenylphosphine sulfide (PS) with 1,3,5-triiodo-2,4,6-trifluorobenzene (I3F), triphenylphosphine sulfide (P...

Activating both Halogen and Chalcogen Bonding Interactions in Cation Radical Salts of Iodinated Tetrathiafulavalene Derivatives.

Halogen bonding (XB) interactions are investigated in cation radical salts of bis(methylthio)-5,5'-diiodotetrathiafulvalene (1). Electrocrystallization of 1 in the presence of Bu4 NCl affords a 1 : 1 salt formulated as (E-1)Cl. Particularly strong I⋅⋅⋅Cl- XB interactions are observed around the Cl- anion with the distances at 78 % the sum of the van der Waals radii, a consequence of the XB charge activation in the cation radical. Moreover, the Cl- environment is complemented by two extra S⋅⋅⋅Cl- chalcogen bonding (ChB) interactions, an original feature among reported halide salts of TTF derivatives. Electrostatic potential calculations on the cation radical further demonstrate the efficient activation of the S atoms of the 1,3-dithiole rings (Vs,max =87.2 kcal/mol), as strong as with the iodine atoms (Vs,max =87.9 kcal/mol). The radical cations form weakly dimerized stacks, as confirmed by the variable-temperature magnetic susceptibility and the weak conductivity (4.8×10-5 S cm-1 ).

Molecular Design and Operational Stability: Toward Stable 3D/2D Perovskite Interlayers.

Despite organic/inorganic lead halide perovskite solar cells becoming one of the most promising next‐generation photovoltaic materials, instability under heat and light soaking remains unsolved. In this work, a highly hydrophobic cation, perfluorobenzylammonium iodide (5FBzAI), is designed and a 2D perovskite with reinforced intermolecular interactions is engineered, providing improved passivation at the interface that reduces charge recombination and enhances cell stability compared with benchmark 2D systems. Motivated by the strong halogen bond interaction, (5FBzAI)2PbI4 used as a capping layer aligns in in‐plane crystal orientation, inducing a reproducible increase of ≈60 mV in the V oc, a twofold improvement compared with its analogous monofluorinated phenylethylammonium iodide (PEAI) recently reported. This endows the system with high power conversion efficiency of 21.65% and extended operational stability after 1100 h of continuous illumination, outlining directions for future work.