XB Interactions Research Articles

Intermolecular Interactions between Halogen-Substituted p-Benzoquinones and Halide Anions: Anion-π Complexes versus Halogen Bonding.

Intermolecular interactions between halo-substituted p-benzoquinones (BQ) and halide anions were examined in solution, solid-state and/or in silico. While X-ray crystallography revealed only halogen bonding (XB) between tetraiodo-p-benzoquinone (I4 Q) and halides, the results of a UV-Vis study in solutions were consistent with the formation of 1 : 1 anion-π complexes. DFT computations showed that the anion-π complexes of halides with most halo-substituted BQ molecules were more stable (by 2-7 kcal/mol) than their XB analogues, but the stabilities of different complexes of I4 Q were essentially the same. Thus, the structural features of the co-crystals with I4 Q were related to multicenter XB interactions between BQs and halides, thus leading to the formation of 3D networks. The observation of anion-π complexes in solutions was attributed to their higher molar absorptivity (by more than an order of magnitude) than that of their XB analogues. Overall, the stabilities of anion-π and XB complexes between BQs and halides were well correlated with the values of highest electrostatic potentials on the surfaces of BQ molecules when their polarizations were taken into account.

Halogen Bonding Interactions of Polychlorinated Biphenyls and the Potential for Thyroid Disruption.

Polychlorinated biphenyl (PCB) flame retardants are persistent pollutants and inhibit neurodevelopment, particularly in the early stages of life. Halogen bonding (XB) to the iodothyronine deiodinases (Dio) that modulate thyroid hormones (THs) is a potential mechanism for endocrine disruption. Cl⋅⋅⋅Se XB interactions of PCBs with SeMe- , a small model of the Dio active site selenocysteine, are compared with previous results on polybrominated diphenylethers (PBDEs) and THs using density functional theory. PCBs generally display weaker XB interactions compared to PBDEs and THs, consistent with the dependence of XB strength on the size of the halogen (I>Br>Cl). PCBs also do not meet a proposed energy threshold for substrates to undergo dehalogenation, suggesting they may behave as competitive inhibitors of Dio in addition to other mechanisms of endocrine disruption. XB interactions in PCBs are position-dependent, with ortho interactions slightly more favorable than meta and para interactions, suggesting that PCBs may have a greater effect on certain classes of Dio. Flexibility of PCBs around the biphenyl C-C bond is limited by ortho substitutions relative to the biphenyl linkage, which may contribute to the ability to inhibit Dio and other TH-related proteins.

Reactions Catalyzed by 2-Halogenated Azolium Salts: From Halogen-Bond Donors to Brønsted-Acidic Salts

Our research group has developed a variety of organocatalysts, especially bi- and multi-functional hydrogen-bond (HB)-donor catalysts. Since 2013, we have become interested in halogen-bond (XB) interactions in organic synthesis, and we have focused on the development of organocatalysts using XBs. Although it is difficult to develop otherwise inaccessible transformations using XBs as the primary interaction, we found several unique reactions that use XB interactions in combination with co-catalysts such as trimethylsilyl iodide, Proton Sponge, and Schreiner’s thiourea. During the synthesis of various 2-iodoazolium salts that can serve as XB donors, a ‘protonated’ 2-iodoazolium salt (a Brønsted-acidic salt) was unexpectedly obtained instead of the corresponding ‘alkylated’ 2-iodoazolium salt (XB donor). The obtained Brønsted-acidic salt is unprecedentedly effective for the N-glycosylation of amides. This account summarizes our findings in this area to date.1 Introduction2 Organoiodine-Compound-Mediated Semipinacol Rearrangement via C–X Bond Cleavage3 2-Iodoazolium-Salt-Catalyzed Reactions through Halogen Bonding (XB)3.1 TMSI-Co-catalyzed Dehydroxylative Coupling of Alcohols with ­Organosilanes3.2 Base-Co-catalyzed Umpolung Alkylation of Oxindoles with an ­Iodonium(III) Ylide3.3 Thiourea-Co-catalyzed N-Glycofunctionalization of Amides3.4 Thiourea-Co-catalyzed N-α-Glycosylation of Amides4 Catalytic Reactions Using 2-Haloazolium Salts as the Brønsted Acids4.1 N-β-Glycosylation of Amides4.2 N-β-2-Deoxyglycosylation of Amides5 Conclusions

Pseudo-Gated Adsorption with Negligible Volume Change Evoked by Halogen-Bond Interaction in the Nanospace of MOFs.

The enhancement of gas adsorption utilizing weak interactions in porous compounds is highly demanding for the design of energy-efficient storage materials. Here, we present a rational design for such an adsorption process by using synergistic functions between dynamic motion in a local module and weak but specific host-guest interactions, that is, halogen-bond (XB) interactions in metal-organic frameworks (MOFs). We designed a new porous coordination polymer (PCP), that is, Br-PCP, the pore surfaces of which are decorated with -CH2 Br groups and could be useful for interaction with CO2 molecules. In accordance with our anticipation, in-situ studies suggest that the adsorption step at approximately 54 kPa during CO2 adsorption is indeed facilitated by XB interactions with little change in the structural volume. This approach of integrating flexible XB modules in rigid PCPs is applicable for designing advanced gas storage systems.

Computational insight into the halogen bonded self-assembly of hexa-coordinated metalloporphyrins.

We demonstrate herein a computational study probing the influence of metalloporphyrins on intermolecular halogen bonding (XB) during supramolecular self-assembly. The results demonstrate that porphyrin aromatic rings can activate or deactivate halogen bonding interactions, especially those on axial ligands, and further influence the preference type of halogen···halogen bonding during the supramolecular self-assembly. Calculations show that the halogen atom present at the equatorial position has a higher sigma hole potential (VS,max) than that at the axial position. The computational analysis and our observations from the X-ray structure analysis are in good agreement. From structural analysis it is clear that equatorial halogen atoms prefer to participate in Type-II XB interactions whereas the axial halogen atoms either participate in Type-I XB interaction or reluctant to participate in XB interactions due to the decrease of their sigma hole potential. Thus, we demonstrate, herein, for the first time a computational study probing the direct influence of the porphyrin's ring current on the sigma hole potential (VS,max) of the halogen atoms and subsequently the effects of the supramolecular self-assembly.

Pnictogen, chalcogen, and halogen bonds in catalytic systems: theoretical study and detailed comparison.

Although halogen bond (XB), a typical σ-hole noncovalent interaction, has been widely exploited in organocatalysis within the last two decades, only very recently has its sister σ-hole interactions, such as chalcogen bond (ChB) and pnictogen bond (PnB), begun to be explored for potential applications in catalysis. Herein, a detailed comparison investigation of PnB, ChB, and XB interactions in catalytic systems was performed from a theoretical point of view. Owing to the excellent properties of the pentafluorophenyl moiety (C6F5) in catalysis, the complexes of (C6F5)3Pn, (C6F5)2Ch, and C6F5X with chloride ion were firstly studied. Then, we successively substituted C6F5 by phenyl groups, to examine the influence of substituents on the characteristics of such interactions. In addition, several halogen-bonded complexes between the donor 1,3,5-trifluoro-2,4,6-triiodobenzene (C6F3I3) and heavier Pn and Ch species as acceptors were also investigated. Our calculations showed that the interactions become gradually stronger upon going from row 3 to 5 and from main group VII to V, which correlates well with the experimental observations. As the strength of the interactions enhances, the contribution of electrostatics to the attraction increases, while the orbital term contribution becomes smaller. Particularly, the significant differences between the three types of σ-hole interactions found in catalysis and anion transport were clarified.

Halogen bonding for increasing efficiency in liquid-liquid microextraction: Application to the extraction of hexabromocyclododecane enantiomers in river water

Halogen bonding (XB) was here proposed, for the first time, as a solubilization mechanism for increasing efficiency in the liquid-liquid microextraction of halogenated compounds. The approach was illustrated by the extraction of hexabromocyclododecane (HBCD) enantiomers in natural waters with a supramolecular solvent (SUPRAS) made up of inverted hexagonal aggregates of decanoic acid. The XB and dispersion interactions offered by the SUPRAS were able to extract the six HBCD enantiomers (i.e. (+)-α-, (-)-α- (+)-β-, (-)-β-, (+)-γ- and (-)-γ-) quantitatively (e.g. recoveries in the range 89–106%) and reach concentration factors as high as 720 without the need for solvent evaporation. HBCD enantiomers in the SUPRAS extract were directly analysed by chiral liquid chromatography coupled to tandem mass spectrometry (LCMS/MS). Quantitation limits of the method (0.09-0.9 ng L−1) were below the quality standard stablished by the European Union for HBCDs in inland surface water samples (1.6 ng L−1), and the precision, expressed as relative standard deviation (n = 6), was below 9% for all the HBCD enantiomers at concentrations within the range 50–500 ng L−1. The method was successfully applied to the enantioselective determination of HBCDs in the dissolved and the particle-bound fractions of river waters containing different concentration of suspended particles (10–57.8 mg L−1) that were spiked at two concentration levels (10 and 100 ng L−1). The results here obtained prove that XB is a valuable mechanism for the solubilisation of halogenated compounds that can effectively increase their recovery from liquid and solid samples.

Theoretical ab Initio Study on Cooperativity Effects between Nitro π-hole and Halogen Bonding Interactions.

This article analyzes the interplay between nitro's π-hole and halogen-bonding (XB) interactions in nitroarenes. Remarkable cooperativity effects are observed when π-hole and XB interactions coexist in the same complex. The nitroarene presents two π-holes, one approximately over the N atom of the nitro group and the other over the aromatic ring, being the former more positive. The interplay between both interactions has been analyzed in terms of energetic and geometric features of the complexes, which are computed at the RI-MP2/def2-TZVPD level of theory. Molecular electrostatic potential (MEP) surface calculations have been used to explore the variation of the MEP values at the π-hole upon the formation of halogen bonding interactions between the nitroarene and CF3 X (X=Cl, Br and I) molecules. In addition, the Bader's theory of atoms in molecules" (AIM) is used to characterize the interactions by means of the distribution of bond critical points and bond paths and to analyze their strengthening or weakening depending upon the variation of charge density at critical points. The aforementioned computational methods are adequate to examine how these interactions mutually influence each other. Natural bond orbital (NBO) and noncovalent interaction plot (NCIPlot) computational tools have been also used in some representative complexes to further analyze cooperativity effects. Finally, the Cambridge Structural Database (CSD) is used to provide some experimental evidence.

Improved Modeling of Halogenated Ligand-Protein Interactions Using the Drude Polarizable and CHARMM Additive Empirical Force Fields.

Halogenated ligands can participate in nonbonding interactions with proteins via halogen bond (XB) or halogen-hydrogen bond donor (X-HBD) interactions. In the context of molecular dynamics (MD) simulations, the accuracy of the simulations depends strongly on the force field (FF) used. To ensure good reproduction of XB and X-HBD interactions with proteins, we optimized the previously developed additive CHARMM36/CHARMM General force field (CGenFF) and Drude polarizable force field by including atom pair-specific Lennard-Jones parameters for aromatic halogen-protein interactions. The optimization targeted quantum mechanical interaction energy surfaces with the developed parameters then examined for their ability to reproduce experimental halogen-containing ligand-protein interactions in MD simulations. The calculated halogenated ligand interaction geometries were in good overall agreement with the experimental crystal data for both the polarizable and additive FFs, showing that these models can accurately treat both XB and X-HBD interactions. Analysis of the ligand-protein interactions shows significant contributions of polarizability to binding occurring in the Drude FF, with self-polarization energy making both favorable and unfavorable contributions to binding. Further analysis of the dipole moments from aqueous solution to protein indicates the polarizable FF accounts for subtle changes of the environment of the ligands that can impact binding. The present work demonstrates the utility of the updated additive CHARMM36/CGenFF and polarizable Drude FFs for the study of halogenated ligand-protein interactions in computer-aided drug design.

Halogen Bonding in Ring‐Substituted Group 10 POCOP Iodido Complexes with Iodine and Its Possible Role in Oxidative Addition

Halogen bonding (XB) of an isostructural series of complexes of the type [3,5‐tBu(tBuPOCOPtBu)MI] [3,5‐tBu2(tBuPOCOPtBu) = κ3‐C6H‐3,5‐(tBu)2‐2,6‐(OPtBu2)2; M = Ni, Pd, Pt] with iodine as XB donor was studied in the solid state. Co‐crystallization experiments afforded single crystals for all three XB systems [3,5‐tBu(tBuPOCOPtBu)NiI] (1‐I2), [3,5‐tBu(tBuPOCOPtBu)PdI] (2‐I2), and [3,5‐tBu(tBuPOCOPtBu)PtI] (3‐I2). Whereas in the case of1‐I2, two molecules of I2bind to the iodide ligand, complexes2‐I2and3‐I2are isostructural 1:1 adducts with almost orthogonal binding of I2to the metal iodido acceptor. All adducts form zig‐zag chain structures where the pincer complexes act as bifunctional XB acceptors, forming XB interactions between metal iodide ligand and I2as well as between the aryl backbone of the pincer ligand and the I2XB donor. DFT studies were performed to analyze the electronic structure of the XB adducts. Halogen bonded adducts and related products of I2coordination were examined as formal intermediates in oxidative addition of I2to a metal(II) center. Computational data suggest that the herein described complexes do not play a role in this context.

Improvement of the Photophysical Performance of Platinum-Cyclometalated Complexes in Halogen-Bonded Adducts.

Three groups of luminescent platinum complexes [Pt(C^N)(L)(Y)] [C^N=benzothienyl-pyridine (1), bezofuryl-pyridine (2), phenyl-pyridine (3); L/Y=DMSO/Cl (a), PPh3 /Cl (b), PPh3 /CN (c)] have been probed as halogen-bond (XB) acceptors towards iodofluorobenzenes (IC6 F5 and I2 C6 F4 ). Compounds 1 a and 2 a (L/Y=DMSO/Cl) afford the adducts 1 a⋅⋅⋅I2 C6 F4 and 2 a⋅⋅⋅I2 C6 F4 , which feature I⋅⋅⋅Sbtpy /I⋅⋅⋅πbtpy and I⋅⋅⋅ODMSO /I⋅⋅⋅Cl short contacts, respectively. The phosphane-cyanide derivatives 1 c and 2 c (L/Y=PPh3 /CN) co-crystallise with both IC6 F5 and I2 C6 F4 . None of the phpy-based species 3 a-3 c participated in XB interactions. Although the native complexes are rather poor luminophores in the solid state (Φem =0.023-0.089), the adducts exhibit an up to 10-fold increase of the intensity with a minor alteration of the emission energy. The observed gain in the quantum efficiency is mainly attributed to the joint influence of non-covalent interactions (halogen/hydrogen bonding, π-π stacking), which govern the crystal-packing mode and diminish the radiationless pathways for the T1 →S0 transition by providing a rigid environment around the chromophore.

Directed Molecular Structure Variations of Three-Dimensional Halogen-Bonded Organic Frameworks (XBOFs)

In this study we have used a tetrahedral oligopyridine and four different fluoroiodides to obtain three-dimensional (3D) nanoporous halogen-bonded cocrystals. Many of the halogen-bonded cocrystals reported to date are one-dimensional chains or two-dimensional sheet-like structures; these new cocrystals possess multiple channels of 300–800 Å3 volume per unit cell. The extended 3D channels can be designed by varying the molecular structure of the halogen bond donor and were found to occupy 20–40% of the unit cell volume. The N···I distances in our cocrystals are ∼80% of the sum of the van der Waals radii of the nitrogen and iodine atoms, and the N···I–C angles are nearly linear. Noncovalent stacking (π–π) interactions as well as H-bonding to solvents were also observed in some of the cocrystals. The supramolecular structures obtained in this study are effectively derived out of different donor–acceptor XB interactions, solvent and other noncovalent interactions. The weak nature of halogen bonds as well as the existence of multiple interactions make these cocrystal structures and their supramolecular organization difficult to predict. Even though this work does not attempt to single out the individual contributions of different factors affecting the supramolecular assemblies, we show here how the structure and hence the potential porosity of the halogen-bonded organic frameworks can be varied via careful design and combination of structurally different donors and acceptors.

Halogen bonds in 2,5-dihalopyridine-copper(ii) chloride complexes

In the (2,5-dihalopyridine)2·CuCl2complexes varying the C5-position halogens affects the halogen bonding properties so that the C5–X5⋯Cl–Cu halogen bonds follow the order F5 < Cl5 < Br5 < I5 when the substituent at 2-position is chlorine and Cl5 < Br5 < I5 when it is bromine.

Enantioselective Anion Recognition by Chiral Halogen-Bonding [2]Rotaxanes.

The application of chiral interlocked host molecules for discrimination of guest enantiomers has been largely overlooked, which is surprising given their unique three-dimensional binding cavities capable of guest encapsulation. Herein, we combined the stringent linear geometric interaction constraints of halogen bonding (XB), the noncovalent interaction between an electrophilic halogen atom and a Lewis base, with highly preorganized and conformationally restricted chiral cavities of [2]rotaxanes to achieve enantioselective anion recognition. Representing the first detailed investigation of the use of chiral XB rotaxanes for this purpose, extensive 1H NMR binding studies and molecular dynamics (MD) simulation experiments revealed that the chiral rotaxane cavity significantly enhances enantiodiscrimination compared to the non-interlocked free axle and macrocycle components. Furthermore, by examining the enantioselectivities of a family of structurally similar XB [2]rotaxanes containing different combinations of chiral and achiral macrocycle and axle components, the dominant influence of the chiral macrocycle in our rotaxane design for determining the effectiveness of chiral discrimination is demonstrated. MD simulations reveal the crucial geometric roles played by the XB interactions in orientating the bound enantiomeric anion guests for chiral selectivity, as well as the critical importance of the anions' hydration shells in governing binding affinity and enantiodiscrimination.

The role of halogen bonding in improving OFET performance of a naphthalenediimide derivative

Controlling microstructure and thin film morphology of organic semiconductors by supramolecular arrangement is critical to improving their device performance. To realize well-controlling supramolecular assembly, a core-expanded naphthalene diimides derivative (1) was designed and synthesized as an n-type organic semiconductor and also as a halogen bonding (XB) donor that could form complementary XBs with 2,2-dipyridine or 2,2-bipyrimidine acceptor. The XB interactions in the solid state of 1/2,2-dipyridine and 1/2,2-bipyrimidine were confirmed by a series of characterization methods, such as thermal gravimetric analysis (TGA), X-ray photoelectron spectroscopy (XPS), nuclear magnetic resonance (NMR) involving 19F NMR and solid-state 13C NMR. Organic field-effect transistors (OFETs) based on XB complexes 1/2,2-dipyridine or 1/2,2-bipyrimidine showed better device performance than that of devices based on pure 1, with the average electron mobility increased more than doubled (from 0.027cm2V−1s−1 to 0.070cm2V−1s−1).

Halogen-Bonding Interactions of Polybrominated Diphenyl Ethers and Thyroid Hormone Derivatives: A Potential Mechanism for the Inhibition of Iodothyronine Deiodinase.

Polybrominated diphenyl ethers (PBDEs) increase flame resistance in consumer goods, but these compounds and their hydroxylated derivatives (OH-BDEs) impair normal thyroid function. Halogen bonding (XB) of PBDEs to an active site selenocysteine may prevent iodothyronine deiodinase(Dio)-catalyzed activation/deactivation of thyroid hormone (TH) derivatives. In this study, we compare the strength of the XB interactions of TH derivatives, iodine-based contrast agents and PBDEs/OH-BDEs with a methylselenolate model of the Dio active site using density functional theory calculations. The strength of the XB interaction depends upon the acceptor halide, the position of the halide, the number of ring substituents, and the proximity of hydroxyl groups to the XB site. The weaker Se⋅⋅⋅Br interactions relative to Se⋅⋅⋅I interactions are consistent with a model of competitive inhibition that blocks binding of THs at elevated PBDE/OH-BDE concentrations. XB interactions were generally more favorable at ortho and meta positions and in substrates with more electron-withdrawing substituents. PBDEs/OH-BDEs that mimic the binding behavior of THs, that is, containing ortho and meta bromides and adjacent hydroxyl groups, may be the most effective inhibitors. Highly-brominated PBDEs/OH-BDEs have comparable interaction energies to THs and may undergo debromination. These results may also suggest that XB strength must exceed a threshold value in order for PBDEs/OH-BDEs to undergo nucleophilic attack by Dio.

Probing covalency in halogen bonds through donor K-edge X-ray absorption spectroscopy: polyhalides as coordination complexes.

The properties of halogen bonds (XBs) in solid-state I2X- and I4X- materials (where X = Cl, Br) are explored using donor K-edge X-ray absorption spectroscopy (XAS) to experimentally determine the degree of charge transfer in such XB interactions. The degree of covalency in these bonds is substantial, even in cases where significantly weaker secondary interactions are observed. These data, in concert with previous work in this area, suggests that certain halogen bonds have covalent contributions to bonding that are similar to, and even exceed, those observed in transition metal coordinate bonds. For this reason, we suggest that XB interactions of this type be denoted in a similar way to coordination bonds (X → Y) as opposed to using a representation that is the same as for significantly less covalent hydrogen bonds (XY).

Comparison of halogen bonding networks with Ru(ii) complexes and analysis of the influence of the XB interactions on their reactivity.

Coordination compounds of formula [Ru(Cl)2(CNR)4] are interesting building blocks for the preparation of halogen bonding supramolecular networks, since the chloride ligand is a good XB acceptor. When using I2 as the XB donor, an unexpected reaction on the ruthenium coordination sphere happens where the chloride ligands are substituted by iodides. The isolation of several intermediates with different substitution degrees and showing XB interactions in a solid state network evidenced the clear influence of the XB species in this unusual reaction process. The extension of the studies to bromine gave the analogous result, i.e. the substitution of the chloride ligands by bromides. Furthermore, changing the organic substituent in the isocyanide ligands from alkyl to aryl does not affect the outcome of the reaction; however the process is faster when the alkyl substituents are present. In the course of the study of these reactions we have isolated a whole range of XB-based networks were interactions such as ClI-I, BrBr-Br, II-I and IBr-Br are present, a systematic comparison of the XB structural features for the different networks isolated and the influence in their reactivity has been performed.

Hydrogen- and halogen-bond cooperativity in determining the crystal packing of dihalogen charge-transfer adducts: a study case from heterocyclic pentatomic chalcogenone donors

A synergic cooperation between HB and XB interactions determines the supramolecular architectures in dihalogen CT adducts of hydantoin-like chalcogen donors.

Elucidating the Effects of Fluoro and Nitro Substituents on Halogen Bond Driven Assemblies of Pyridyl-Capped π-Conjugated Molecules

Among recent advances toward efficient semiconducting materials, rational design guidelines have emerged focusing on the synergy between various intermolecular interactions to improve the solid-state order of π-conjugated molecules in organic electronic devices. Herein, we focus our attention on halogen bonding (XB) interactions and the crucial role of electron withdrawing substituents (e.g., nitro and fluoro) toward influencing solid-state properties via secondary interactions. Employing iodoethynyl benzene derivatives (F2BAI and (NO2)2BAI) and thiophene/furan-based building blocks equipped with pyridyl groups as self-assembling domains (PyrTF and PyrT2), co-crystals driven by XB and π-stacking interactions were formed and studied. Spectroscopic and thermal analysis of 1:1 mixtures provide initial evidence of co-crystallization. X-ray crystallography affords the inherent solid-state packing motifs within each assembly. Computational studies support experimental observations, revealing the dominant intera...