Dominik Cinčić

A Stepwise Mechanism for the Mechanochemical Synthesis of Halogen-Bonded Cocrystal Architectures

A molecular-level mechanism is proposed for two cases of mechanochemical cocrystallization via halogen bonds. The proposed stepwise mechanism is based on the observation and structural characterization of intermediates that appear in early stages of the reaction. The mechanism arises from the competition of strong and weak intermolecular halogen bonds of the N...I and S...I type and involves the initial formation of finite molecular assemblies, held together via N...I bonds that subsequently polymerize into infinite chains by cross-linking through S...I bonds. This mechanism has been observed in the synthesis of linear as well as zigzag halogen-bonded chain architectures.

A cocrystallisation-based strategy to construct isostructural solids

Cocrystallisation provides a means for dissimilar functional groups to become structurally equivalent, i.e. adopt similar structural roles in the solid. We describe a strategy to systematically construct sets of isostructural solids by using this cocrystallisation-induced structural equivalence. The strategy utilises cocrystallisation to combine different types of structurally equivalent functionalities in the solid state and enlarge an already existing set of isostructural cocrystals from two to four members. Halogen-bonded cocrystals of acridine (acr) and phenazine (phen) with iodopentafluorobenzene (ipb) form a pair of isostructural solids related by cocrystallisation-induced structural equivalence of aromatic CH and N groups. Structural equivalence of halogen-bonded Br and I groups allowed the replacement of ipb in these cocrystals with its bromo analogue, bromopentafluorobenzene (bpb), without disturbing the cocrystal architecture. Consequently, combining structurally equivalent groups allowed the construction of a set of four solids based on the same supramolecular blueprint.

Experimental and database studies of three-centered halogen bonds with bifurcated acceptors present in molecular crystals, cocrystals and salts

We present a database and experimental study of three-centered halogen bonds involving bifurcated halogen bond acceptors. Our study encompasses three cocrystals with nitrogen, oxygen and sulfur atoms as acceptors and iodine atoms as donors, as well as an overview of three-centered halogen-bonded systems contained within the Cambridge Structural Database based on organic iodine as the donor atom and nitrogen, oxygen, fluorine, sulfur, chlorine, bromine or iodine atoms as acceptors. The results demonstrate that three-centered halogen bonding arrangements are a possible outcome of cocrystallisation experiments and that they exhibit well-defined geometries. The occurrence of such three-centered interactions is considerably rarer for halogen bonds than for hydrogen bonds and, at the current level of understanding, their formation cannot be readily predicted. The strong preference for binary two-center interactions makes a clear difference between halogen and hydrogen bonds. However, as potential guidelines towards developing halogen-bonded architectures based on bifurcated acceptors, the database search indicates particular preference for bifurcation of neutral sulfur or anionic chloride and bromide acceptors.

Synthesis, crystal structure determination and antiproliferative evaluation of novel benzazoyl benzamides

A series of benzazoyl-benzamides containing different substituents 7-17 were synthesized by condensation of 2-aminobenzazole derivatives 3a-6 with p-substituted benzoyl chlorides. All compounds were characterized by IR, 1H and 13C NMR, MS and elemental analysis. Crystal structure was determined for the compound 9. Some of the new synthesized compounds 7-17 were screened for antitumor activities. Based on presented in vitro screening results we may conclude that compounds 10, 15a, 15b and 16 showed accentuated cell growth inhibitory activity.

Schiff base derived from 2-hydroxy-1-naphthaldehyde and liquid-assisted mechanochemical synthesis of its isostructural Cu(II) and Co(II) complexes

The Schiff base ligand derived from 2-hydroxy-1-naphthaldehyde, namely 1-[(2-biphenylamino)methylen]naphthalen-2(1H)-one (1) and its corresponding Cu(II) and Co(II) complexes (2 and 3, respectively) were synthesized and characterised by means of IR spectroscopy, thermal analysis and also by powder and single crystal X-ray diffraction. The mononuclear complexes have been obtained by a conventional solution-based method as well as by a mechanochemical method, i.e. by liquid-assisted grinding. The molecule of 1 is not planar and the keto-amino tautomer was detected from the molecular geometry consideration. The discrete molecules are π-stacked in the [100] direction and connected by weak intermolecular interactions. Compounds 2 and 3 are isostructural. The form of the copper atom coordination polyhedron is irregular square planar while the form of the cobalt atom coordination polyhedron is irregular tetrahedral. Both complexes form 1D chains in the [010] direction by weak C–H⋯O and C–H⋯C interactions.

Synthesis of an extended halogen-bonded metal–organic structure in a one-pot mechanochemical reaction that combines covalent bonding, coordination chemistry and supramolecular synthesis

We describe a four-component one-pot mechanochemical reaction which combines the formation of covalent bonds, coordination bonds and halogen bonds to obtain an extended structure based on halogen-bonded metal–organic units.

Halogen and Hydrogen Bonding between (N‐Halogeno)succinimides and Pyridine Derivatives in Solution, the Solid State and in Silico

A study of strong halogen bonding within three series of halogen-bonded complexes, derived from seven para-substituted pyridine derivatives and three N-halosuccinimides (iodo, bromo and chloro), has been undertaken with the aid of single-crystal diffraction, solution complexation and computational methods. The halogen bond was compared with the hydrogen bond in an equivalent series based on succinimide. The halogen-bond energies are in the range -60 to -20 kJ mol-1 and change regularly with pyridine basicity and the Lewis acidity of the halogen. The halogen-bond energies correlate linearly with the product of charges on the contact atoms, which indicates a predominantly electrostatic interaction. The binding enthalpies in solution are around 19 kJ mol-1 less negative due to solvation effects. The optimised geometries of the complexes in the gas phase are comparable to those of the solid-state structures, and the effects of the supramolecular surroundings in the latter are discussed. The bond energies for the hydrogen-bonded series are intermediate between the halogen-bond energies of iodine and bromine, although there are specific differences in the geometries of the halogen- and hydrogen-bonded complexes.

Uncommon halogen bond motifs in cocrystals of aromatic amines and 1,4-diiodotetrafluorobenzene

A number of novel halogen-bonded aromatic amine cocrystals with 1,4-diiodotetrafluorobenzene have been synthesized via both mechanochemical and solution syntheses, offering valuable insight into potential halogen bond acceptor species.

Polymorphism control in the mechanochemical and solution-based synthesis of a thermochromic Schiff base

Three crystal forms of a thermochromic Schiff base, namely 1-{3-[(2-hydroxy-3-methoxy-benzylidene)-amino]-phenyl}-ethanone, derived from o-vanillin and 3-aminoacetophenone, were obtained by conventional solution-based methods. Two out of the three polymorphs were synthesized by mechanochemical syntheses, under solvent-free conditions. Herein, we report a study of the dependence of the composition of solvent, the crystallization temperature and impurities on the outcome of the synthesis of Schiff base polymorphs. We report the important role of seed crystals in directing the supramolecular organization of the product of a covalent solvent-free reaction towards the intended polymorphic outcome as well. All obtained polymorphs were investigated by means of thermal analysis, single crystal X-ray diffraction, ex situ and in situ powder X-ray diffraction and IR spectroscopy. The polymorphs display interesting and remarkably different molecular packing arrangements governed by C–H⋯O interactions leading to two-dimensional networks in forms I and III, and a three-dimensional networks in form II.

Halogen bonding of N-bromosuccinimide by grinding

Two halogen bonded cocrystals of N-bromosuccinimide and 4,4′-bipyridine, with stoichiometric ratios 1:1 and 2:1, have been synthesized and characterized. We present the first mechanochemical cocrystallization of N-bromosuccinimide.