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Unraveling the binding preferences involved in the formation of a supramolecular complex is key to properly understand molecular recognition and aggregation phenomena, which are of pivotal importance to biology. The halogenation of nucleic acids has been routinely carried out for decades to assist in their X-ray diffraction analysis. The incorporation of a halogen atom on a DNA/RNA base not only affected its electronic distribution, but also expanded the noncovalent interactions toolbox beyond the classical hydrogen bond (HB) by incorporating the halogen bond (HalB). In this regard, an inspection of the Protein Data Bank (PDB) revealed 187 structures involving halogenated nucleic acids (either unbound or bound to a protein) where at least 1 base pair (BP) exhibited halogenation. Herein, we were interested in disclosing the strength and binding preferences of halogenated A···U and G···C BPs, which are predominant in halogenated nucleic acids. To achieve that, computations at the RI-MP2/def2-TZVP level of theory together with state of the art theoretical modeling tools (including the computation of molecular electrostatic potential (MEP) surfaces, the quantum theory of "Atoms in Molecules" (QTAIM) and the non-covalent interactions plot (NCIplot) analyses) allowed for the characterization of the HB and HalB complexes studied herein.

The term matere bond has been recently used to refer to an attractive noncovalent interaction between any element of group 7 acting as an electrophile and any atom (or group of atoms) acting as a nucleophile. The utilization of metals such as σ-hole donors is starting to attract the attention of the scientific community. In this manuscript, a comparison between matere bonds and well-known σ-hole interactions (halogen and chalcogen bonds) is carried out using three X-ray structures, retrieved from the Cambridge structural database (CSD), and density functional theory calculations (DFT). The novelty of this work resides in the utilization of a neutral Re(VII) system as the matere bond donor and multivalent chalcogen and halogen donors. In fact, as far as our knowledge extends, the description of σ-hole interactions in Se(VI) is unprecedented in the literature. The σ-hole interactions in Re(VII), Se(VI) and Cl(VII) electron acceptors are analyzed and compared using several computational tools.

The X-ray structure of 2-(dibromomethyl)benzonitrile, featuring unexpectedly short C≡N⋯Br halogen bond distances between a nitrile group and a C(sp3)-linked bromine atom, is presented. Despite the weak Lewis base nature of the nitrile N atom and absence of strong electron-withdrawing groups on the Br atom, π-stacking significantly enhances both the electron donor and acceptor capability of the interacting partners. As such, and beyond trivial (hetero)aromatic systems, the rationale of C ≡N⋯B r halogen bonding can also be employed in purely aliphatic systems. [ABSTRACT FROM AUTHOR]

Two new metal–organic multi-component compounds of Ni(II) and Co(II), viz. [Ni(3-CNpy)2(H2O)4]ADS·2.75H2O (1) and [Co(3-CNpy)2(H2O)4](4-ClbzSO3)2 (2) (3-CNpy = 3-cyanopyridine, ADS = anthraquinone-1,5-disulfonate, 4-ClbzSO3 = 4-chlorobenzenesulfonate), were synthesized and characterized using single crystal XRD, TGA, spectroscopic (IR, electronic) and elemental analyses. Both the compounds crystallize as multi-component compounds of Ni(II) and Co(II), with uncoordinated ADS and 4-ClbzSO3 moieties in the crystal lattice, respectively. Crystal structure analyses revealed the presence of antiparallel nitrile···nitrile and π-stacked assemblies involving alternate coordinated 3-CNpy and uncoordinated ADS and 4-ClbzSO3 moieties. Moreover, unconventional charge reverse Cl∙∙∙N halogen bonding contacts observed in compound 2 provide additional reinforcement to the crystal structure. Theoretical calculations confirm that the H-bonding interactions, along with anion–π(arene) and anion–π(CN) in 1 and π–π, antiparallel CN···CN and charge reverse Cl···N halogen bonds in 2, play crucial roles in the solid state stability of the compounds. In vitro anticancer activities observed through the trypan blue cell cytotoxicity assay reveal that the compounds induce significant concentration dependent cytotoxicity in Dalton's lymphoma (DL) cancer cells, with nominal effects in normal healthy cells. Molecular docking studies reveal that the compounds can effectively bind with the active sites of anti-apoptotic proteins, which are actively involved in cancer progression. [ABSTRACT FROM AUTHOR]

The role of noncovalent interactions (spodium, halogen and hydrogen bonds) in the reaction of [Zn{NH＝C(CCl3)NC(CCl3)＝NH}2] with acetone, pyrazole, 4,4′-bipyridine and Cu(acetylacetonate)2 is reported. Depending on the reactants, different types of organic, coordination and supramolecular compounds were isolated, and various types of noncovalent interactions were disclosed. [ABSTRACT FROM AUTHOR]

In this manuscript, we have examined the CSD (Cambridge Structural Database) to investigate the relative ability of Te and I (in practice, the heaviest chalcogen and halogen atoms) in di- and tri-iododiorganyltellurium(IV) derivatives to establish σ-hole interactions. The geometry around the Te(IV) in this type of compound is trigonal bipyramidal where the stereoactive lone pair at Te(IV) occupies one of the equatorial positions. In the solid state, Te(IV) tends to form pseudo-octahedral coordination by establishing strong noncovalent interactions opposite to the two covalent bonds of the equatorial plane. Such contacts can also be classified as chalcogen bonds following the recommendation of the International Union of Pure and Applied Chemistry (IUPAC). Such contacts have been analyzed energetically in this work using density functional theory (DFT) calculations, rationalized using molecular electrostatic potential (MEP) surface analysis and characterized using a combination of the quantum theory of atoms in molecules (QTAIM) and noncovalent interaction plot (NCIplot) computational tools. Finally, the observation of halogen bonds and type I halogen···halogen contacts is also emphasized and compared to the chalcogen bonds. Energy decomposition analysis has also been performed to compare the physical nature of chalcogen, halogen and type I interactions. [ABSTRACT FROM AUTHOR]

Co‐crystallization of 180°‐orienting σ‐hole‐accepting tectons, namely, 1,4‐diisocyanobenzene (1) and 1,4‐diisocyanotetramethylbenzene (2), with such homoditopic halogen bond donors as 1,4‐diiodotetrafluorobenzene (1,4‐FIB) and 4,4'‐diiodoperfluorobiphenyl (4,4'‐FIBP) afforded co‐crystals 1 ⋅ 1,4‐FIB, 1 ⋅ 4,4'‐FIBP, and 2 ⋅ 1,4‐FIB. Their solid‐state structures exhibit 1D‐supramolecular arrangements, which are based on poorly explored I⋅⋅⋅C halogen bonding; this study is the first in which the supramolecular assembly utilizing halogen bonding with a terminal C atom was performed. The use of the potentially tetrafunctional σ‐hole accepting tetraiodoethylene (TIE) leads to supramolecular architecture of a higher dimension, 3D‐framework, observed in the structure of 1 ⋅ TIE. DFT calculations, used to characterize the halogen bonding situation, revealed that the I⋅⋅⋅C non‐covalent interactions are moderately strong, ranging from −4.07 in 1 ⋅ TIE to −5.45 kcal/mol in 2 ⋅ 1,4‐FIB. The NBO analysis disclosed that LP(C)→σ* charge transfer effects are relevant in all co‐crystals. [ABSTRACT FROM AUTHOR]

This work reports a combined computational and experimental analysis of the ability of square planar d8 transition metal complexes to establish unconventional halogen bonding interactions with chloro-, bromo-, and iodopentafluorobenzene as σ-hole donors. Typical M⋯Ha (M = transition metal and Ha = halogen) interactions are coordination bonds (frequently halides acting as counter ions) or semicoordination bonds (neutral lone pair donor halogens). However, in recent times a new binding mode has been described in the literature with a reverse donor–acceptor role. That is, directional C–Br,I⋯M halogen bonding (HaB) interactions have been reported where the metal center acts as the electron-rich atom and the halogen atom acts as the acceptor via its σ-hole. In addition to the Cambridge Structural Database (CSD) survey of exemplifying X-ray structures, this manuscript reports a DFT study that investigates the relative ability of Ni, Pd, and Pt square planar complexes to participate in HaBs with chloro-, bromo-, and iodopentafluorobenzene. [ABSTRACT FROM AUTHOR]

An interplay between 4‐bromo‐ and 4‐iodo‐5‐nitrophthalonitriles (XNPN, X=Br or I) and any one of the azines (pyridine 1, 4‐dimethylaminopyridine 2, isoquinoline 3, 4‐cyanopyridine 4, 2‐methylpyridine 5, 2‐aminopyridine 6, quinoline 7, 1‐methylisoquinoline 8, and 2,2'‐bipyridine 9) proceeds differently depending on steric and electronic effects of the heterocycles. Sterically unhindered azines 1–3 underwent N‐arylation to give the corresponding azinium salts (characterized by 1H and 13C{H} NMR and high‐resolution ESI‐MS). In contrast, azines 4–9 with sterically hindered N atoms or bearing an electron‐withdrawing substituent, form stable co‐crystals with XNPN, where two interacting molecules are bound by halogen bonding. In all obtained co‐crystals, X⋅⋅⋅N structure‐directed halogen bonds were recognized and theoretically evaluated including DFT calculations (PBE0‐D3/def2‐TZVP level of theory), QTAIM analysis, molecular electrostatic potential surfaces, and noncovalent interaction plot index. Estimated energies of halogen bonding vary from −7.6 kcal/mol (for 6 ⋅ INPN) to −11.4 kcal/mol (5 ⋅ INPN). [ABSTRACT FROM AUTHOR]

This manuscript combines a search in the Cambridge Structural Database (CSD) and theoretical density functional theory (DFT) calculations to analyse the existence and importance of charge assisted pnictogen and halogen bonds involving halophosphonium cations. Trivalent pnictogen atoms typically have three σ-holes and are able to establish up to three pnictogen bonds (PnBs). In phosphonium salts, the phosphorus atom forms four covalent bonds and, consequently, four σ-holes are located at the extension of these bonds. Therefore, up to four charge assisted PnBs can be formed between these holes and the counterions or any electron rich atom. The covalent bond arrangement around the phosphorus atom is similar to that around tetravalent tetrel atoms and converts into a similar pattern of σ-hole interactions. We have found and described this type of charge assisted pnictogen bond in various halophosphonium crystal structures. Moreover, the competition of charge assisted PnBs with charge assisted halogen bonds (HaBs) has been also studied both theoretically and by analysing the CSD. [ABSTRACT FROM AUTHOR]

This manuscript reports the synthesis and X-ray characterization of two octahydro-1H-4,6-epoxycyclopenta[c]pyridin-1-one derivatives that contain the four most abundant halogen atoms (Ha) in the structure with the aim of studying the formation of Ha···Ha halogen bonding interactions. The anisotropy of electron density at the heavier halogen atoms provokes the formation of multiple Ha···Ha contacts in the solid state. That is, the heavier Ha-atoms exhibit a region of positive electrostatic potential (σ-hole) along the C–Ha bond and a belt of negative electrostatic potential (σ-lumps) around the atoms. The halogen bonding assemblies in both compounds were analyzed using density functional theory (DFT) calculations, molecular electrostatic potential (MEP) surfaces, the quantum theory of "atom-in-molecules" (QTAIM), the noncovalent interaction plot (NCIplot), and the electron localization function (ELF). [ABSTRACT FROM AUTHOR]

• Synthesis of pyrazoloquinoline scaffold in excellent yield. • Unraveling the synergistic effects of C-H...O, C-H...N, Cl...O, π...π, Cl...π and CH...π interactions. • Evaluation of energetic features using Hirshfeld analysis and DFT calculations. • Characterization of π-stacking and halogen bonding interactions using QTAIM and NCIPlot methods. • Assessment of urease inhibitory potential using indophenol method. The present study investigates the influence of noncovalent interactions in the design and structural control of crystal packing of pyrazoloquinoline derivative. Compound 3 was prepared in a two-step process in excellent yield. The reaction of 2,7-dichloroquinoline-3-carbaldehyde (1) and hydrazine monohydrate gave access to intermediate 2 which was alkylated regioselectively at the N1 pyrazole nitrogen. The synergistic effects of noncovalent interactions such as H-bonding (C-H...O, C-H...N), halogen bonding (Cl...O) and π-contacts (π...π, Cl...π and CH...π) remained crucial in leading the structural topology of pyrazoloquinoline skeleton. The types of noncovalent interactions was energetically evaluated using Hirshfeld analysis and DFT calculations. The π-stacking and halogen bonding contacts have been studied using QTAIM and NCIPlot techniques. The pharmacological evaluation of compound 3 as anti-urease agent revealed considerably strong potency (IC 50 = 8.51 ± 0.10 µM) when compared with positive control, thiourea. In vitro inhibitory data were confirmed through molecular modeling investigation where several key binding interactions were revealed between pyrazoloquinoline and vital residues inside the binding pocket of urease enzyme. ADME investigation successfully predicted various pharmacokinetic properties satisfying the druggable criteria and presenting the title compound to act as a lead inhibitor of Jack bean urease for further investigations. [Display omitted] QTAIM and NCIPlot for the π-stacked dimer (a) and HB/XB dimer (b) in compound 3. The combination of π-interactions (π...π, Cl...π and CH...π) is evidenced by the NCIplot analysis. The existence of the XB and another one connecting one CH group to the negative belt of the Cl-atom is also confirmed. [ABSTRACT FROM AUTHOR]