Zdeňka Růžičková

Competition between Halogen, Hydrogen and Dihydrogen Bonding in Brominated Carboranes.

Halogen bonds are a subset of noncovalent interactions with rapidly expanding applications in materials and medicinal chemistry. While halogen bonding is well known in organic compounds, it is new in the field of boron cluster chemistry. We have synthesized and crystallized carboranes containing Br atoms in two different positions, namely, bound to C- and B-vertices. The Br atoms bound to the C-vertices have been found to form halogen bonds in the crystal structures. In contrast, Br atoms bound to B-vertices formed hydrogen bonds. Quantum chemical calculations have revealed that halogen bonding in carboranes can be much stronger than in organic architectures. These findings open new possibilities for applications of carboranes, both in materials and medicinal chemistry.

Effect of intercalation and chromophore arrangement on the linear and nonlinear optical properties of model aminopyridine push–pull molecules

Three push–pull aminopyridine derivatives having D–π–A, D–(π–A)2, and D–(π–A)3 arrangements were examined as model organic chromophores capable of intercalation into inorganic layered materials (alpha modification of zirconium hydrogen phosphate, zirconium 4-sulfophenylphosphonate, and gamma modification of titanium hydrogen phosphate). The fundamental properties of these dyes, their methylated analogues as well as their intercalates were studied by X-ray analysis, electrochemistry, UV/Vis absorption spectra, TGA, IR spectra, SHG, and were completed by DFT calculations. The synthesis of tripodal tris(pyridin-4-yl)amine is given for the first time. The HOMO–LUMO gap, the position of the longest-wavelength absorption maxima, and the dipole moment of aminopyridines can easily be tuned by attaching/removing pyridin-4-yl electron withdrawing units and their quaternization (pyridine vs. pyridinium acceptors). Their intercalation proved to be feasible affording novel inorganic–organic hybrid materials. The intercalation is accompanied by protonation of the guest, which enhances its ICT and strongly anchors the aminopyridines into the confined space of the layered host. Moreover, this process results in ordering of the organic chromophores and also brings improved thermal and chemical robustness. As a result, the measured SHG efficiencies of the intercalates are larger than those observed for the pure organic push–pull chromophores. Hence, the methodology of intercalation turned out to be very useful strategy for property tuning of NLO-active organic molecules.

Synthesis, structural characterization, docking, lipophilicity and cytotoxicity of 1-[(1R)-1-(6-fluoro-1,3-benzothiazol-2-yl)ethyl]-3-alkyl carbamates, novel acetylcholinesterase and butyrylcholinesterase pseudo-irreversible inhibitors

In the current study, sixteen novel derivatives of (R)-1-(6-fluorobenzo[d]thiazol-2-yl)ethanamine were synthesized as acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitors. Chemical structures together with purity of the synthesized compounds were substantiated by IR, (1)H, (13)C, (19)F NMR, high resolution mass spectrometry and elemental analysis. The optical activities were confirmed by optical rotation measurements. The synthesized compounds were evaluated for their AChE and BChE inhibitory activities. In addition, the cytotoxicity of the most active compounds was investigated against human cell lines employing XTT tetrazolium salt reduction assay and xCELLigence system allowing a label-free assessment of the cells proliferation. Our results demonstrated that the inhibitory mechanism was confirmed to be pseudo-irreversible, in line with previous studies on carbamates. Compounds indicated as 3b, 3d, 3l and 3n showed the best AChE inhibitory activity of all the evaluated compounds and were up to tenfold more potent than standard drug rivastigmine. The binding mode was determined using state-of-the-art covalent docking and scoring methodology. The obtained data clearly demonstrated that 3b, 3d, 3l and 3n benzothiazole carbamates possess high inhibitory activity against AChE and BChE and concurrently negligible cytotoxicity. In conclusion, our results indicate, that these derivatives could be promising in an effective therapeutic intervention for Alzheimers disease.

Stabilization of η3-indenyl compounds by sterically demanding N,N-chelating ligands in the molybdenum coordination sphere

A series of η3-indenyl molybdenum compounds [(η3-4,7-Me2C9H5)Mo(CO)2(N,NL)Cl] (N,NL = bpy, phen, pyma), isostructural with well-known η3-allyl compounds, was synthesized from the recently established halide synthon [{(η5-4,7-Me2C9H5)Mo(CO)2(μ-Cl)}2]. The low stability of the hexacoordinated η3-indenyl molybdenum species in solution has been overcome by a modification of the chelating ligand. Hence, the dissociation of the compounds bearing ligands with methyl groups beside nitrogen donor atoms (e.g. 6,6′-Me2-bpy, 2,9-Me2-phen; 2,9-Me2-4,7-Ph2-phen) is strongly disfavored due to the steric requirements of the substituents. The considerable discrimination of the pentacoordinated species enables the use of [(η5-4,7-Me2C9H5)Mo(CO)2(2,9-Me2-phen)][BF4] for the assembly of derivatives bearing other halides and pseudohalides in the coordination sphere of molybdenum. The current study further describes some other new indenyl complexes accessible from [{(η5-4,7-Me2C9H5)Mo(CO)2(μ-Cl)}2]. All structural types presented in this experimental study were supported by X-ray crystallographic data.

Pnictogen bonding in pyrazine•PnX 5 (Pn = P, As, Sb and X = F, Cl, Br) complexes

AbstractThis paper presents a study of pnictogen bonding in a series of pyrazine•PnX5 (Pn = P, As, Sb and X = F, Cl, Br) complexes. The whole series was studied computationally. Moreover, the pyrazine complexes with PCl5 and SbCl5 were prepared and characterized experimentally. It was found that the Pn-N distances are only slightly elongated when compared to the sum of covalent radii. The conformation of PnX5 changed considerably upon the complex formation, which resulted in a significant change of the dipole moment of the PnX5 fragment and a considerably more positive σ-hole on the pnictogen atom. Finally, interaction energies were decomposed in order to provide a deeper insight into the nature of the studied pnictogen-bonded complexes. Graphical abstractThe conformation of PnX5 changed considerably upon the complex formation, which resulted in a considerably more positive σ-hole on the pnictogen atom.

Unique Stereocontrol in Carborane Chemistry: Skeletal Alkylcarbonation (SAC) versus Exoskeletal Alkylmethylation (EAM) Reactions†

Reactions between the arachno-6,9-C2B8H14 (1) dicarbaborane and acyl chlorides, RCOCl (2), are subject to stereocontrol that completely changes the nature of the reaction products. While most chlorides produce the 8-R-nido-7,8,9-C3B8H11 (3) tricarbollides (by skeletal alkylcarbonation=SAC), bulky RCOCls (2; where R=1-adamantyl, 2 a; 1-mesityl, 2 b; 9-anthranyl, 2 c; 1-naphthyl, 2 d) in 1,2-dichloroethane (DCE) in the presence of triethylamine at 40-60 °C gave a series of entirely different 1-R-2-CH3-closo-1,6-C2B8H8 (4) dicarbaboranes upon acidification with conc. H2SO4 (by exosleletal alkylmehylation=EAM). Both types of reactions seem to proceed via a common [8-R-nido-7,8,9-C3B8H10](-) (3(-)) anion which in the EAM case is unstable because of steric crowd and undergoes rearrangement via the isomeric [R-nido-7,8,10-C3B8H10](-) tricarbollide structures which, on protonation, undergo reductive extraction of one CH vertex to generate the 2-CH3 substituent in structure 4.

Synthesis, structural characterization, antimicrobial and antifungal activity of substituted 6-fluorobenzo[d]thiazole amides

A series of novel 1-[(1R)-1-(6-fluoro-1,3-benzothiazol-2-yl)ethyl]-3-substituted phenyl amides was synthesized by the condensation reaction of (1R)-1-(6-fluoro-1,3-benzothiazol-2-yl)ethanamine with substituted benzoyl chlorides under mild conditions. Their structures were confirmed by 1H NMR, 13C NMR and 19F NMR spectra, elemental analyses and in three cases also by single-crystal X-ray diffraction techniques. The optical activities were confirmed by optical rotation measurements. All the synthesized compounds were screened for antibacterial and antifungal activity against a variety of bacterial and fungal strains. Some of the compounds reveal antibacterial and antifungal activity comparable or slightly better to that of chloramphenicol, cefoperazone and amphotericin B used as medicinal standards.

C,N-Chelated organotin(iv) azides: synthesis, structure and use within click chemistry

A set of tri- and diorganotin(IV) azides bearing 2-(N,N-dimethylaminomethyl)phenyl as a C,N-chelating ligand (LCN) has been prepared and structurally characterized. Triorganotin(IV) azides of the type LCNR2SnN3 (R = n-Bu (1) and Ph (2)) and (LCN)2(n-Bu)SnN3 are monomeric both in solution and in the solid state. The central tin atom in these species is five-coordinated with distorted trigonal bipyramidal geometry. Diorganotin(IV) azides of the type LCNRSn(N3)2 (R = n-Bu and Ph) are monomeric with trigonal bipyramidal geometry around the tin atom as well. Finally, (LCN)2Sn(N3)2 contains a six-coordinated tin atom with heavily distorted octahedral geometry due to the presence of two LCN units. The potential use of selected organotin(IV) azides 1 and 2 as useful building blocks within click chemistry was investigated. The reactions of 1 and 2 with various nitriles resulted in the formation of corresponding triorganotin(IV) tetrazolides (i.e. κ-N1: LCN(n-Bu)2Sn(5-MeCN4), LCNPh2Sn(5-MeCN4), LCN(n-Bu)2Sn(5-Me2NCH2CN4), LCNPh2Sn(5-Me2NCH2CN4); and κ-N2: LCN(n-Bu)2Sn(5-t-BuCN4), LCNPh2Sn(5-t-BuCN4), LCN(n-Bu)2Sn(5-PhCN4), LCNPh2Sn(5-PhCN4)). Similarly, the reaction of 1 and 2 with cyclooctyne provided corresponding C,N-chelated di-n-butyl/diphenyltin(IV) κ-N1 4,5,6,7,8,9-hexahydrocycloocta[d][1,2,3]triazol-1-ides. All azido complexes and products of the [3+2] cycloaddition reactions were characterized by the combination of elemental analysis, mass spectrometry, IR spectroscopy, multinuclear NMR spectroscopy and, in the case of crystalline materials, XRD analysis. In addition, DFT calculations were carried out within the click chemistry reactions in order to corroborate the preferred formation of the respective tetrazolide regioisomer.

Different structural types of copper(II) furan- and thiophencarboxylates: X-ray structural, EPR, spectral and magnetic analyses

Synthesis and characterization of eight new complexes of various structural types are reported. With 5-nitro-2-furancarboxylic acid (5-NO2-2-fucH), two monomeric complexes, [Cu(5-NO2-2-fuc)2(H2O)2] (II) and [Cu(5-NO2-2-fuc)2(H2O)4] (III), as well as a dimeric complex with ethylnicotinate (Etnic), [Cu(5-NO2-2-fuc)2(Etnic)2]2 (V), were prepared. With other acids: 2,5-dimethyl-3-furancarboxylic acid (2,5-Me2-3-fucH), 2-thiophencarboxylic acid (2-tpcH), 3-methyl-2-thiophencarboxylic acid (3-Me-2-tpcH) or 5-methyl-2-thiophencarboxylic acid (5-Me-2-tpcH), only dimeric complexes [Cu(2,5-Me2-3-fuc)2(H2O)]2 (I), [Cu(2,5-Me2-3-fuc)2(Etnic)]2 (IV), [Cu(2-tpc)2(Etnic)]2 (VI), [Cu(3-Me-2-tpc)2(Etnic)]2 (VII) and Cu(5-Me-2-tpc)2(Etnic)]2 (VIII) have been synthesised. Characterizations of the complexes were based on elemental analysis and infrared, electronic, EPR and magnetic measurements. Moreover, complexes III, V, VII and VIII were also studied by X-ray structural analysis. Two structural types of dimeric complexes were observed differing in the number of carboxylate bridges. Most of the dinuclear complexes exhibit the common “paddle-wheel” structural motif while the molecular structure of V contains two pentacoordinated copper(II) ions bridged by two carboxylate groups of two 5-nitro-2-furancarboxylate ligands resulting in the intramolecular copper-copper distance of 4.4960(8) Å. Magnetic properties (monomeric EPR signal and isotropic exhchange constant (J of approximately 0 cm−1) of V confirmed a very weak magnetic interaction between copper centres.

An intramolecular C–N cross-coupling of β-enaminones: a simple and efficient way to precursors of some alkaloids of Galipea officinalis

Summary 2-Aroylmethylidene-1,2,3,4-tetrahydroquinolines with the appropriate substituents can be suitable precursors for the synthesis of alkaloids from Galipea officinalis (cuspareine, galipeine, galipinine, angustureine). However, only two, rather low-yielding procedures for their synthesis are described in the literature. We have developed a simple and efficient protocol for an intramolecular, palladium or copper-catalysed amination of both chloro- and bromo-substituted 3-amino-1,5-diphenylpent-2-en-1-ones leading to the above-mentioned tetrahydroquinoline moiety. The methodology is superior to the methods published to date.