Strong Halogen Bonds Research Articles

Crystallographic Evidence for Bi(I) as the Heaviest Halogen Bond Acceptor.

Complexation of the green bismuthinidene (RBi) with two equivalents of a highly fluorinated aryl iodide at low temperature allows the crystallographic identification of an unstable red species that can be regarded as an intermediate in an overall Bi(I) → Bi(III) oxidation process. Both C-I bonds are orientated toward the filled 6p orbital of bismuth (Bi-I distances 3.44-3.52 Å), leading to an elongation of the C-I bonds by 0.05 and 0.07 Å. Density functional theory (DFT) calculations confirm that the Bi(I) center is indeed acting as an electron donor, establishing two strong and directional halogen bonds. The color change from green to red upon halogen bond formation is a consequence of the energetic stabilization of a Bi(I) lone pair by interactions with the sigma-holes of the halogen bond donors. Overall, this study presents the first structural proof of bismuth, and more generally of heavy organopnictogen(I) compounds, acting as halogen bond acceptors.

Halogen Bonding in N-Alkyl-bromo-/iodo-pyridinium Salts and its Application in Chromatography.

The alkylation of 3-/4-bromo- and -iodopyridine with methyl triflate smoothly affords the correspondingN-methylpyridinium triflate salts. An anion exchange with NaI or [PPh4]Y (Y = Cl, Br, I) yields the corresponding halide salts. Most of them could be structurally characterized and their strong halogen bonds were investigated. While the halogen atom of 4-halogenopyridinium is susceptible to nucleophilic substitution, 3-halogenopyridinium ions are far more stable against nucleophilic attacks. Due to the comparable interaction strength of halogen bonds and hydrogen bonds, the latter of which is widely used in chromatography, the potential of 3-halogenopyridinium moieties for an application in chromatography is obvious and wassuccessfully employed in affinity chromatography of differentproteins.

The Halogen Bond to Ethers - Prototypic Molecules and Experimental Electron Density.

Halogen bonds to dialkyl ether molecules have remained largely unexplored. We here address the synthesis and the structural chemistry of the first halogen-bonded noncyclic alkyl ethers, combining 1,4-diiodotetrafluorobenzene and the prototypic or commonly used ethers dimethyl ether, tetrahydrofuran, and methyl-tert-butyl ether as halogen acceptors. Two different structural motifs based on moderately strong halogen bonds were obtained: Discrete trimolecular aggregates are formed, and unexpected halogen-bonded supramolecular chain adducts feature oxygen-bifurcated halogen bonds with 1:1 donor:acceptor ratio. Both structure types may be selectively obtained even for the same ether by adjusting the stoichiometry in the crystallization experiments. The geometric features of the etheric oxygen center were found to be flexible, in contrast to the almost linear geometry about the halogen donor atom. A high-resolution X-ray diffraction experiment on the extended adduct of dimethyl ether allowed us to study the electronic details of the acceptor-bifurcated I···O···I halogen bonds. The electron density in the bond critical points and derived properties such as the Laplacian indicate essentially electrostatic interactions and explain the geometrical flexibility of ethers in halogen bonds. Our studies demonstrate the great versatility of ethers as halogen bond acceptors, that can occur in many geometrical arrangements and whose contribution to nature's structural designs should not be underestimated.

Occupied-Virtual Orbitals for Chemical Valence with Applications to Charge Transfer in Energy Decomposition Analysis.

In this article, we introduce the occupied-virtual orbitals for chemical valence (OVOCV). The OVOCVs can replace or complement the closely related idea of the natural orbitals for chemical valence (NOCV). The input is a difference density matrix connecting any initial single determinant to any final determinant, at a given molecular geometry, and a given one-particle basis. This arises in problems such as orbital rearrangement or charge transfer (CT) in energy decomposition analysis (EDA). The OVOCVs block-diagonalize the density difference operator into 2 × 2 blocks, which are spanned by one level that is filled in the initial state (the occupied OVOCV) and one that is empty (the virtual OVOCV). By contrast, the NOCVs fully diagonalize the density difference matrix and therefore are orbitals with mixed occupied-virtual character. Use of the OVOCVs makes it much easier to identify the donor and acceptor orbitals. We also introduce two different types of EDA methods with the OVOCVs and, most importantly, a charge decomposition analysis method that fixes the unreasonably large CT amount obtained directly from NOCV analysis. The square of the CT amount associated with each NOCV pair emerges as the appropriate value from the OVOCV analysis. When connecting the same initial and final states, this value is identical to the CT amount obtained from the independent absolutely localized molecular orbital (ALMO) complementary occupied-virtual orbital pair (COVP) analysis. The total, summed over all pairs, is also exactly the same as the independently suggested excitation number, as proved herein. Several examples are presented to compare NOCVs and OVOCVs: stretched H2+, a strong halogen bond between tetramethylthiourea and iodine, coordination of ethene in Zeise's salt, and binding in the Cp3La···C≡NCy complex.

Computational investigation of amide derivative as potential anti-carbapenem-resistant Pseudomonas aeruginosa

Recent findings indicate a surge in morbidity and mortality probabilities associated with infections caused by carbapenem-resistant strains, underscoring an urgent need for the development of effective drugs against these strains. This study employs Density Functional Theory (DFT) with the ωB97XD/6–311++G (2d, 2p) model to investigate the electronic, structural, and the biological potential of N1, N10-Bis (1,3,4-thiadiazolo (3,2-a)pyridine-2-yl)-decanediamide (TDZ). Fourier Transform Infrared Spectroscopy highlights significant assignments related to C-H, C=C, and N=H functionalities, aligning well with experimental results. Chemical reactivity analysis orders the energy gap as TDZ_Acetone > TDZ_Gas > TDZ_DMSO > TDZ_Water. The visualization of weak interaction in wider regions of steric repulsions are seen for TDZ in solvents DMSO, acetone and water as well as transformation of strong halogen bonds to van der Waals interaction. Visual findings reveal the propensity of the compound to form hydrogen bonds with protein targets due to high electron localization around hydrogen atoms. Pharmacokinetics studies indicate TDZ's favorable intestinal absorption at 50.525 %. Moreover, TDZ does not inhibit hERG 1, eliminating the risk of potassium channel blocking-induced cardiac arrhythmia. Molecular docking analysis shows TDZ's enhanced biological activity and stronger binding affinity with 5XNW, with a binding affinity of −4.5 kcal/mol and the formation of five conventional hydrogen bonds. Comparatively, for 4AKX, the standard drug Dori records eight hydrogen bond interactions at −6.8 kcal/mol, while TDZ records nine interactions at −8.6 kcal/mol. This suggests that, despite Dori's favorable interactions and good biological activity, TDZ exhibits superior binding affinity and heightened biological activity potential, positioning it as a promising drug candidate against carbapenem-resistant Pseudomonas aeruginosa infections.

Directionality of Halogen-Bonds: Insights from 2D Energy Decomposition Analysis.

Halogen bonds are typically observed to have a linear arrangement with a 180° angle between the nucleophile and the halogen bond acceptor X-R. This linearity is commonly explained using the σ-hole model, although there have been alternative explanations involving exchange repulsion forces. We employ two-dimensional Distortion/Interaction and Energy Decomposition Analysis to examine the archetypal H3 N⋯X2 halogen bond systems. Our results indicate that although halogen bonds are predominantly electrostatic, their directionality is largely due to decreased Pauli repulsion in linear configurations as opposed to angled ones in the I2 and Br2 systems. As we move to the smaller halogens, Cl2 and F2 , the influence of Pauli repulsion diminishes, and the energy surface is shaped by orbital interactions and electrostatic forces. These results support the role of exchange repulsion forces in influencing the directionality of strong halogen bonds. Additionally, we demonstrate that the 2D Energy Decomposition Analysis is a useful tool for enhancing our understanding of the nature of potential energy surfaces in noncovalent interactions.

Enhanced iodine capture by the hydrogen bond reconstruction strategy

The strong intramolecular hydrogen-bond of curcumin was broken by ionization, and curcumin anions form a weaker intermolecular hydrogen bond which is easily disrupted, making it easy to react with iodine and form a new strong halogen bond.

Influence of N-protonation on electronic properties of acridine derivatives by quantum crystallography.

Applications of 9-aminoacridine (9aa) and its derivatives span fields such as chemistry, biology, and medicine, including anticancer and antimicrobial activities. Protonation of such molecules can alter their bioavailability as weakly basic drugs like aminoacridines exhibit reduced solubility at high pH levels potentially limiting their effectiveness in patients with elevated gastric pH. In this study, we analyse the influence of protonation on the electronic characteristics of the molecular organic crystals of 9-aminoacridine. The application of quantum crystallography, including aspherical atom refinement, has enriched the depiction of electron density in the studied systems and non-covalent interactions, providing more details than previous studies. Our experimental results, combined with a topological analysis of the electron density and its Laplacian, provided detailed descriptions of how protonation changes the electron density distribution around the amine group and water molecule, concurrently decreasing the electron density at bond critical points of N/O-H bonds. Protonation also alters the molecular architecture of the systems under investigation. This is reflected in different proportions of the N⋯H and O⋯H intermolecular contacts for the neutral and protonated forms. Periodic DFT calculations of the cohesive energies of the crystal lattice, as well as computed interaction energies between molecules in the crystal, confirm that protonation stabilises the crystal structure due to a positive synergy between strong halogen and hydrogen bonds. Our findings highlight the potential of quantum crystallography in predicting crystal structure properties and point to its possible applications in developing new formulations for poorly soluble drugs.

Ortho-Substituent Effects on Halogen Bond Geometry for N-Haloimide⋯2-Substituted Pyridine Complexes.

The nature of (imide)N-X⋯N(pyridine) halogen-bonded complexes formed by six N-haloimides and sixteen 2-substituted pyridines are studied using X-ray crystallography (68 crystal structures), Density Functional Theory (DFT)(86 complexation energies), and NMR spectroscopy (90 association constants). Strong halogen bond (XB) donors such as N-iodosuccinimide form only 1:1 haloimide:pyridine crystalline complexes, but even stronger N-iodosaccharin forms 1:1 haloimide:pyridine and three other distinct complexes. In 1:1 haloimide:pyridine crystalline complexes, the haloimide's N─X bond exhibits an unusual bond bending feature that is larger for stronger N-haloimides. DFT complexation energies (ΔEXB ) for iodoimide-pyridine complexes range from -44 to -99kJmol-1 , while for N-bromoimide-pyridine, they are between -31 and -77kJmol-1 . The ΔEXB of I⋯N XBs in 1:1 iodosaccharin:pyridine complexes are the largest of their kind, but they are substantially smaller than those in [bis(saccharinato)iodine(I)]pyridinium salts (-576kJmol-1 ), formed by N-iodosaccharin and pyridines. The NMR association constants and ΔEXB energies of 1:1 haloimide:pyridine complexes do not correlate as these complexes in solution are heavily influenced by secondary interactions, which DFT studies do not account for. Association constants follow the σ-hole strengths of N-haloimides, which agree with DFT and crystallography data. The haloimide:2-(N,N-dimethylamino)pyridine complex undergoes a halogenation reaction resulting in 5-iodo-2-dimethylaminopyridine.

Efficient capture of iodine by charge-induced effect of nitrogen-rich ionic liquids

The efficient capture of radioactive iodine in nuclear waste is vital for promoting the sustainable development of nuclear energy, protecting the environment and human health. Nitrogen-rich adsorbents have received widespread attention due to their high affinity with iodine. Herein, we present a series of nitrogen-rich heterocyclic ionic liquids based on 5-aminotetrazolate (ATILs), and fabricate four composite materials ([N1111][AT]/MF, [N2222][AT]/MF, [N3333][AT]/MF, [N4444][AT]/MF). MF with porous properties as a carrier is cost-effective and readily available. For the composite materials, the ATILs possess abundant nitrogen active sites, and the introduction of MF significantly increases their specific surface area. This greatly enhances the iodine capture performance of materials. The maximum capture capacities of [N1111][AT]/MF, [N2222][AT]/MF, [N3333][AT]/MF and [N4444][AT]/MF were 6.94 g g−1, 6.53 g g−1, 5.70 g g−1 and 4.58 g g−1, respectively. A certain correlation between capture performance and nitrogen content can be found. Increasing the nitrogen content of material can still contribute to enhancing its performance, even when the nitrogen content exceeds 35 %. FT-IR, Raman and XPS spectra confirmed that the polyiodide anions were produced via charge-inductive effect and charge transfer. The density functional theory (DFT) calculation confirmed the feasibility of nitrogen-rich strategies and the existence of strong halogen bonds between I2 and 5-aminotetrazolate anions. This work obtained a series of iodine capture materials with high nitrogen content, achieved efficient iodine capture, and demonstrated the relationship between materials with high nitrogen content and iodine adsorption performance, which will promote the design and development of novel nitrogen-rich materials for iodine capture.

Synthesis and characterization of a new chalcone-based nonlinear optical crystal: BBC

A new chalcone-based nonlinear optical crystal BBC (C22H17BrO2) using long π-conjugated and halogen substituent, as a potential alternative to develop organic crystals, are reported. BBC was designed and synthesized by replacing benzyloxy and -Br groups on both sides of molecular framework. Flaky yellowish BBC single crystal with size of 5 × 5 × 1 mm3 was grown by solution evaporation method. BBC crystal crystallizes in the monoclinic system, Pc (NO. 7) space group, with noncentrosymmetric structure. In the BBC molecule, benzyl oxide acts as donor (D) and Br and carbonyl group act as acceptor (A), forming D - π - A - π - A structure with electron gradient. The introduction of Br group, which contributes to strong halogen bond formation, lead to the “head-to-tail” arrangement. Remarkably, BBC exhibits strong second harmonic generation (SHG) intensity (14 × KDP and 2.2 × Urea), wide transmission range (600-1600 nm, >60%), high optical energy gap (Eg=2.85 eV) and high thermal stability (Tm=106 °C). In addition, to investigate the relationships between the structure and physical properties, the electronic structure and optical properties of BBC crystal were theoretically calculated. This work not only provides a newly chalcone-based NLO crystal, but also presents a feasible molecular design approach by introducing long π-conjugated and halogen substituents.

Mixed-Halide Perovskites with Halogen Bond Induced Interlayer Locking Structure for Stable Pure-Red PeLEDs.

Mixed-halide perovskites enable precise spectral tuning across the entire spectral range through composition engineering. However, mixed halide perovskites are susceptible to ion migration under continuous illumination or electric field, which significantly impedes the actual application of perovskite light-emitting diodes (PeLEDs). Here, we demonstrate a novel approach to introduce strong and homogeneous halogen bonds within the quasi-two-dimensional perovskite lattices by means of an interlayer locking structure, which effectively suppresses ion migration by increasing the corresponding activation energy. Various characterizations confirmed that intralattice halogen bonds enhance the stability of quasi-2D mixed-halide perovskite films. Here, we report that the PeLEDs exhibit an impressive 18.3% EQE with pure red emission with CIE color coordinate of (0.67, 0.33) matching Rec. 2100 standards and demonstrate an operational half-life of ∼540 min at an initial luminance of 100 cd m-2, representing one of the most stable mixed-halide pure red PeLEDs reported to date.

Gauging the Strength of the Molecular Halogen Bond via Experimental Electron Density and Spectroscopy.

Strong and weak halogen bonds (XBs) in discrete aggregates involving the same acceptor are addressed by experiments in solution and in the solid state. Unsubstituted and perfluorinated iodobenzenes act as halogen donors of tunable strength; in all cases, quinuclidine represents the acceptor. NMR titrations reliably identify the strong intermolecular interactions in solution, with experimental binding energies of approx. 7 kJ/mol. Interaction of the σ hole at the halogen donor iodine leads to a redshift in the symmetric C-I stretching vibration; this shift reflects the interaction energy in the halogen-bonded adducts and may be assessed by Raman spectroscopy in condensed phase even for weak XBs. An experimental picture of the electronic density for the XBs is achieved by high-resolution X-ray diffraction on suitable crystals. Quantum theory of atoms in molecules (QTAIM) analysis affords the electron densities and energy densities in the bond critical points of the halogen bonds and confirms stronger interaction for the shorter contacts. For the first time, the experimental electron density shows a significant effect on the atomic volumes and Bader charges of the quinuclidine N atoms, the halogen-bond acceptor: strong and weak XBs are reflected in the nature of their acceptor atom. Our experimental findings at the acceptor atom match the discussed effects of halogen bonding and thus the proposed concepts in XB activated organocatalysis.

Halogen Bond to Experimentally Significant N-Heterocyclic Carbenes (I, IMe2, IiPr2, ItBu2, IPh2, IMes2, IDipp2, IAd2; I = Imidazol-2-ylidene).

The subjects of the article are halogen bonds between either XCN or XCCH (X = Cl, Br, I) and the carbene carbon atom in imidazol-2-ylidene (I) or its derivatives (IR2) with experimentally significant and systematically increased R substituents at both nitrogen atoms: methyl = Me, iso-propyl = iPr, tert-butyl = tBu, phenyl = Ph, mesityl = Mes, 2,6-diisopropylphenyl = Dipp, 1-adamantyl = Ad. It is shown that the halogen bond strength increases in the order Cl < Br < I and the XCN molecule forms stronger complexes than XCCH. Of all the carbenes considered, IMes2 forms the strongest and also the shortest halogen bonds with an apogee for complex IMes2⋯ICN for which D0 = 18.71 kcal/mol and dC⋯I = 2.541 Å. In many cases, IDipp2 forms as strong halogen bonds as IMes2. Quite the opposite, although characterized by the greatest nucleophilicity, ItBu2 forms the weakest complexes (and the longest halogen bonds) if X ≠ Cl. While this finding can easily be attributed to the steric hindrance exerted by the highly branched tert-butyl groups, it appears that the presence of the four C-H⋯X hydrogen bonds may also be of importance here. Similar situation occurs in the case of complexes with IAd2.

Experimental spectral investigations for structural, electronic, topological properties and molecular docking studies of 2-cyclohexylidene hydrazine carbaxamide

The compound 2-cyclohexylidene hydrazine carbaxamide (2CHHC) was investigated and analyzed using computational analyses based on DFT. The molecular structure and geometry were evaluated. The 2CHHC's FT-IR and FT–Raman spectra are obtained. Topographic characteristics including Laplacian electron density are being estimated by AIM theory. The NBO evaluation method is used to find donor-acceptor interactions. ELF and LOL were being used to quantify the electron density at bonding and anti - bonding sites. NCI analysis demonstrates the presence of weak Van der Waals interactions, strong attractive hydrogen and halogen bonds and repulsive steric interactions in the compound. The reactivity descriptor and Fukui functions are anticipated to depict the chemical reactivity premises of 2CHHC. The optimal ligand protein interactions of 2CHHC were reported using docking analysis.

Halogen bonding between metal-bound I3− and unbound I2: the trapped I2⋯I3− intermediate in the controlled assembly of copper(i)-based polyiodides

The identification of halogen bonded-intermediates is key to understanding the precise mechanism for the generation of I5− (and I82−) ligands from I2 and metal-coordinated I3−.

Dichlorinated Organic‐Salt Terahertz Sources for THz Spectroscopy

AbstractAlthough in terahertz (THz) source materials molecular anions significantly influence the performance of THz generation, only limited classes of molecular counter anions have been reported. Here, utilizing dichlorinated molecular anions in THz generators is reported for the first time, to the best of our knowledge. In these new crystals, two dichlorinated molecular anions with different molecular symmetries, asymmetric 3,4‐dichlorobenzenesulfonate (34DCS) and symmetric 3,5‐dichlorobenzenesulfonate (35DCS), are incorporated with a 2‐(4‐hydroxystyryl)‐1‐methylquinolinium (OHQ) cation possessing top‐level molecular optical nonlinearity. OHQ‐34DCS exhibits a strong nonlinear optical response, in contrast to OHQ‐35DCS. In OHQ‐34DCS crystals, the dichlorinated groups form strong halogen bonds (XBs) and hydrogen bonds (HBs), which are beneficial for suppressing molecular (phonon) vibrations. The optical‐to‐THz conversion efficiency of the OHQ‐34DCS crystals is extremely high, comparable to that of the benchmark organic THz generators. Moreover, the THz emission spectra from the OHQ‐34DCS crystals, compared to those of previously reported benchmark analogous crystals, are stronger modulated toward a flatter shape, but possess substantially reduced spectral dimples. Therefore, the introduction of dichlorinated molecular anions is an efficient approach for the design of highly efficient electro‐optic salt crystals as efficient broadband THz wave sources.

Enhanced Optoelectronic Performances of the Cocrystals between 2,2′-Bi(1,8-naphthyridine) and Iodine through Strong Halogen Bonds

Enhanced Optoelectronic Performances of the Cocrystals between 2,2′-Bi(1,8-naphthyridine) and Iodine through Strong Halogen Bonds

Bending properties in the 4-halobenzonitrile crystals and C-halogen...N[triple-bond]C halogen bonds.

The single crystal of 4-iodobenzonitrile (C7H4IN) is brittle, whereas those of 4-bromobenzonitrile (C7H4BrN) and one of the two forms of 4-chlorobenzonitrile (C7H4ClN) are compliant in nature. The chloro crystal exhibits elastic bending, but in spite of having stronger halogen bonds, the bromo crystal exhibits plastic bending. Crystal structures have been analyzed to understand the different bending properties of these three crystals. In all three cases, the molecules form C-X...N[triple-bond]C (X= halogen) halogen-bonded chains in their respective crystal structures. Statistical analyses and DFT calculations on the C-X...N[triple-bond]C halogen bonds reveal that the optimum geometry of all three halogen bonds is linear and the C-I...N[triple-bond]C bond is strongest among the three. However, when the geometry deviates from linearity, the energy loss is very high in the case of the C-I...N[triple-bond]C bond compared to the other two systems. This explains why 4-iodobenzonitrile is brittle, whereas the other two are flexible. The interactions in 4-bromobenzonitrile are more isotropic than those in 4-chlorobenzonitrile. The iodo and chloro compounds crystallize in centrosymmetric space groups, whereas the crystal of the bromo compound lacks inversion symmetry. In spite of this difference in their space groups, the chloro and bromo crystals have very similar crystal packing. In the case of the bromo crystal, the halogen-bonded chains are parallel to the bending axis (long axis) of the crystal. However, these chains are significantly tilted in the case of the chloro crystal. The isotropic/anisotropic interactions, presence/absence of an inversion centre and the different alignment of the halogen-bonded chains with respect to the bending axis could explain the different bending properties of the chloro and bromo crystals.

Unexpectedly significant stabilizing mechanism of iodous acid on iodic acid nucleation under different atmospheric conditions

Iodous acid (HIO2) has been shown to play a stabilizing role in the nucleation of iodic acid (HIO3) (He et al., 2021). However, the stabilization effect and specific stabilizing mechanism of HIO2 on HIO3 nucleation under different atmospheric conditions remain unclear. Therefore, we studied these two issues under different temperatures and nucleation precursor concentrations using density functional theory combined with the Atmospheric Cluster Dynamics Code. We found that HIO2 can form clusters with HIO3 via strong hydrogen bonds, halogen bonds, and proton-transfer, substantially enhancing the stability of HIO3 clusters and decreasing the energy barrier of HIO3-based cluster formation at different temperatures and nucleation precursor concentrations. The particle formation rate and cluster concentrations of HIO3–HIO2 nucleation were negatively correlated with temperature and positively correlated with HIO2 concentration. The enhancements by HIO2 on the particle formation rate and cluster concentration of HIO3 nucleation were positively correlated with temperature and HIO2 concentration. Interestingly, even at a low HIO2 concentration (1.0 × 105 molecules cm−3), the enhancement on the particle formation rate and cluster concentration of HIO3 nucleation by HIO2 were both unexpectedly up to 4.1 × 104-fold at 283 K. Therefore, HIO3–HIO2 nucleation can be extremely rapid in cold regions, and the enhancement by HIO2 can be significant, especially in warm regions even at relatively high HIO2 concentrations.