The Ruthenium Nitrosyl Moiety in Clusters: Trinuclear Linear µ-Hydroxido Magnesium(II)-Diruthenium(II), µ3-Oxido Trinuclear Diiron(III)-Ruthenium(II), and Tetranuclear µ4-Oxido Trigallium(III)-Ruthenium(II) Complexes.

The ruthenium nitrosyl moiety, {RuNO}6, is important as a potential releasing agent of nitric oxide and is of inherent interest in coordination chemistry. Typically, {RuNO}6 is found in mononuclear complexes. Herein we describe the synthesis and characterization of several multimetal cluster complexes that contain this unit. Specifically, the heterotrinuclear µ3-oxido clusters [Fe2RuCl4(µ3-O)(µ-OMe)(µ-pz)2(NO)(Hpz)2] (6) and [Fe2RuCl3(µ3-O)(µ-OMe)(µ-pz)3(MeOH)(NO)(Hpz)][Fe2RuCl3(µ3-O)(µ-OMe)(µ-pz)3(DMF)(NO)(Hpz)] (7·MeOH·2H2O) and the heterotetranuclear µ4-oxido complex [Ga3RuCl3(µ4-O)(µ-OMe)3(µ-pz)4(NO)] (8) were prepared from trans-[Ru(OH)(NO)(Hpz)4]Cl2 (5), which itself was prepared via acidic hydrolysis of the linear heterotrinuclear complex {[Ru(µ-OH)(µ-pz)2(pz)(NO)(Hpz)]2Mg} (4). Complex 4 was synthesized from the mononuclear Ru complexes (H2pz)[trans-RuCl4(Hpz)2] (1), trans-[RuCl2(Hpz)4]Cl (2), and trans-[RuCl2(Hpz)4] (3). The new compounds 4-8 were all characterized by elemental analysis, ESI mass spectrometry, IR, UV-vis, and 1H NMR spectroscopy, and single-crystal X-ray diffraction, with complexes 6 and 7 being characterized also by temperature-dependent magnetic susceptibility measurements and Mössbauer spectroscopy. Magnetometry indicated a strong antiferromagnetic interaction between paramagnetic centers in 6 and 7. The ability of 4 and 6-8 to form linkage isomers and release NO upon irradiation in the solid state was investigated by IR spectroscopy. A theoretical investigation of the electronic structure of 6 by DFT and ab initio CASSCF/NEVPT2 calculations indicated a redox-noninnocent behavior of the NO ancillary ligand in 6, which was also manifested in TD-DFT calculations of its electronic absorption spectrum. The electronic structure of 6 was also studied by an X-ray charge density analysis.

Design of High-Performance Pyridine/Quinoline Hydrazone Photoswitches.

The design of P-type photoswitches with thermal stability of the metastable form of hundreds of years that would efficiently transform using excitation wavelengths above 350 nm remains a challenge in the field of photochromism. In this regard, we designed and synthesized an extended set of 13 pyridine/quinoline hydrazones and systematically investigated the structure-property relationships, defining their kinetic and photoswitching parameters. We show that the operational wavelengths of the pyridine hydrazone structural motif can be effectively shifted toward the visible region without simultaneous loss of their high thermal stability. Furthermore, we characterized the ground-state and excited-state potential energy surfaces with quantum-chemical calculations and ultrafast transient absorption spectroscopy, which allowed us to rationalize both the thermal and photochemical reaction mechanisms of the designed hydrazones. Whereas introducing an electron-withdrawing pyridyl moiety in benzoylpyridine hydrazones leads to thermal stabilities exceeding 200 years, extended π-conjugation in naphthoylquinoline hydrazones pushes the absorption maxima toward the visible spectral region. In either case, the compounds retain highly efficient photoswitching characteristics. Our findings open a route to the rational design of a new family of hydrazone-based P-type photoswitches with high application potential in photonics or photopharmacology.

Ni Oxidation State and Ligand Saturation Impact on the Capability of Octaazamacrocyclic Complexes to Bind and Reduce CO2.

Two 15-membered octaazamacrocyclic nickel(II) complexes are investigated by theoretical methods to shed light on their affinity forwards binding and reducing CO2. In the first complex 1[NiIIL]0, the octaazamacrocyclic ligand is grossly unsaturated (π-conjugated), while in the second 1[NiIILH]2+ one, the macrocycle is saturated with hydrogens. One and two-electron reductions are described using Mulliken population analysis, quantum theory of atoms in molecules, localized orbitals, and domain averaged fermi holes, including the characterization of the Ni-CCO2 bond and the oxidation state of the central Ni atom. It was found that in the [NiLH] complex, the central atom is reduced to Ni0 and/or NiI and is thus able to bind CO2 via a single σ bond. In addition, the two-electron reduced 3[NiL]2- species also shows an affinity forwards CO2.

Evaluation of Antiproliferative Palladium(II) Complexes of Synthetic Bisdemethoxycurcumin towards In Vitro Cytotoxicity and Molecular Docking on DNA Sequence.

Metallodrugs form a large family of therapeutic agents against cancer, among which is cisplatin, a paradigmatic member. Therapeutic resistance and undesired side effects to Pt(II) related drugs, prompts research on different metal-ligand combinations with potentially enhanced biological activity. We present the synthesis and biological tests of novel palladium(II) complexes containing bisdemethoxycurcumin (BDMC) 1 and 2. Complexes were fully characterized and their structures were determined by X-ray diffraction. Their biological activity was assessed for several selected human tumor cell lines: Jurkat (human leukaemic T-cell lymphoma), HCT-116 (human colorectal carcinoma), HeLa (human cervix epitheloid carcinoma), MCF-7 (human breast adenocarcinoma), MDA-MB-231 (human mammary gland adenocarcinoma), A549 (human alveolar adenocarcinoma), Caco-2 (human colorectal carcinoma), and for non-cancerous 3T3 cells (murine fibroblasts). The cytotoxicity of 1 is comparable to that of cisplatin, and superior to that of 2 in all cell lines. It is a correlation between IC50 values of 1 and 2 in the eight studied cell types, promising a potential use as anti-proliferative drugs. Moreover, for Jurkat cell line, complexes 1 and 2, show an enhanced activity. DFT and docking calculations on the NF-κB protein, Human Serum Albumin (HSA), and DNA were performed for 1 and 2 to correlate with their biological activities.

Coordination bonding in dicopper and dichromium tetrakis(µ-acetato)-diaqua complexes: Nature, strength, length, and topology.

Geometry optimization, energetics, electronic structure, and topology of electron density of dicopper (I) and dichromium (II) tetrakis(µ-acetato)-diaqua complexes are studied focusing on the metal-metal interactions. The performance of broken symmetry (BS) single-determinant ab initio (Hartree-Fock, Møller-Plesset perturbation theory to the second and third orders, coupled clusters singles and doubles) and density functional theory (BLYP, B3LYP, B3LYP-D3, B2PLYP, MPW2PLYP) methods is compared to multideterminant ab initio (CASSCF, NEVPT2) methods as well as to the multipole model of charge density from a single-crystal X-ray diffraction experiment (Herich et al., Acta Cryst. 2018, B74, 681-692). In vacuo DFT geometry optimizations (improper axial water ligand orientation) are compared against the periodic ones. The singlet state is found to be energetically preferred. J coupling of (I) becomes underestimated for all ab initio methods used, when compared to experiment. It is concluded that the strength of the direct M─M interactions correlates closely with the J coupling magnitude at a given level of theory. The double potential well character of (II) and of the dehydrated form of (II) are considered with respect to the Cr─Cr distance. The physical effective bond order of the metal-metal interaction is small (below 0.1 e) in (I) and moderate (0.4 e) in (II). The CASSCF results overestimate the electron density of the metal-metal bond critical point by 20% and 50% in (I) and (II), respectively, when compared to the multipole model. © 2019 Wiley Periodicals, Inc.

Strong deshielding in aromatic isoxazolines.

Very strong proton deshielding was found in di/tri-aromatic isoxazoline regioisomers prepared from acridin-4-yl dipolarophiles and stable benzonitrile oxides (BNO). Three alkenes, (acridin-4-yl)-CH=CH-R (R = COOCH3, Ph, and CONH2), reacted with three BNO dipoles (2,4,6-trimethoxy, 2,4,6-trimethyl, 2,6-dichloro) to give pairs of target isoxazolines with acridine bound to C-4 or C-5 carbon of the isoxazoline (denoted as 4-Acr or 5-Acr). Regioselectivity was dependent on both the dipolarophile and dipole character. The ester and amide dipolarophile displayed variable regioselectivity in cycloadditions whereas the styrene one afforded prevailing 4-Acr regioisomers. 2,4,6-Trimethoxy-BNO was most prone to form 5-Acr isoxazolines while mesitonitrile oxide gave major 4-Acr isoxazolines. Basic hydrolysis of the amide cycloadduct led to an unexpected isoxazolone product. The structure of the target compounds was studied by NMR, MS, and X-ray crystallography.

Antimicrobial Activity and Urease Inhibition of Schiff Bases Derived from Isoniazid and Fluorinated Benzaldehydes and of Their Copper(II) Complexes.

In order to evaluate the influence of substitution on biological properties of Schiff bases and their metal complexes, a series of differently substituted fluorine-containing Schiff bases starting from the drug isoniazid (isonicotinylhydrazide) were prepared and their structures were established by single-crystal X-ray diffraction. Also, four copper(II) complexes of these Schiff bases were synthesized. The prepared compounds were evaluated for their antimicrobial activity and urease inhibition. Two of the Schiff bases exerted activity against C. albicans. All copper(II) complexes showed excellent inhibitory properties against jack bean urease, considerably better than that of the standard inhibitor acetohydroxamic acid.

Synthesis, crystal structure, spectroscopic properties and potential biological activities of salicylate‒neocuproine ternary copper(II) complexes.

Mixed ligand copper(II) complexes containing derivatives of salicylic acid and heterocyclic ligands with nitrogen donor atoms have been the subject of various studies and reviews. In this paper, synthesis and characterization of the ternary copper(II) complexes of neocuproine (2,9-dimethyl-1,10-phenanthroline, Neo) and salicylate ligands (Sal) are reported. In addition, the crystal structures of ([Cu(H2O)(5-Cl-Sal)(Neo)] (1), [Cu(µ-Sal)(Neo)]2 (2), Cu2(µ-5-Cl-Sal)(5-Cl-HSal)2(Neo)2]·EtOH (3)) were determined. In order to compare structural and biological properties of the prepared complexes, spectroscopic and biological studies were performed. Results of X-ray diffraction show that prepared complexes form three types of crystal structures in a given system: monomeric, dimeric and dinuclear complex. The preliminary study on the DNA cleavage activity has shown that the complexes under study behave as the chemical nucleases in the presence of added hydrogen peroxide with slight differences in the activity (1 > 2 > 3). The complexes 1 and 2 exhibited nuclease activity itself indicating the interaction of complexes with the DNA. It has been proposed that the enhanced destructive effect of the complexes 1 and 2 on the DNA is a result of two possible mechanisms of action: (i) the conversion of closed circular DNA (form I) to the nicked DNA (form II) caused by the copper complex itself and (ii) damage of DNA by Reactive Oxygen Species (ROS)-products of the interaction of copper with hydrogen peroxide by means of Fenton reaction (hydroxyl radicals). Thus the biological activity of the prepared Cu(II) complexes containing derivatives of salicylic acid and phenanthroline molecules is substantiated by two independent mechanisms. While derivatives of salicylic acids in the coordination sphere of copper complexes are responsible for radical-scavenging activity (predominantly towards superoxide radical anion), the presence of chelating ligand 2,9-dimethyl-1,10-phenanthroline significantly enhances capability of Cu(II) complexes binding to DNA via intercalation.

Synthesis, physicochemical properties and antimicrobial activity of mono-/dinitroxyl amides.

Two comparative sets of mono-/dinitroxyl amides were designed and prepared. The novel TEMPO and/or PROXYL derivatives were fully characterised and their spin, redox and antimicrobial properties were determined. Cyclic voltammetry revealed (quasi)reversible redox behavior for most of the studied radicals. Moreover, the electron-withdrawing substituents increased the oxidation potential of nitroxides in comparison to electron-donating groups. While EPR spectra of monoradicals featured the typical three-line signal, the spectra of biradicals showed more complex splitting patterns. The in vitro biological assay revealed that unlike pyrrolidinyl derivatives, the piperidinyl nitroxides significantly inhibited the growth of Staphylococcus sp.

Conformational, spectroscopic, and molecular dynamics DFT study of precursors for new potential antibacterial fluoroquinolone drugs.

Biological activity, functionality, and synthesis of (fluoro)quinolones is closely related to their precursors (for instance 3-fluoroanilinoethylene derivatives) (i.e., their functional groups, conformational behavior, and/or electronic structure). Herein, the theoretical study of 3-fluoroanilinoethylene derivatives is presented. Impact of substituents (acetyl, methyl ester, and ethyl ester) on the conformational analysis and the spectral behavior is investigated. The B3LYP/6-311++G** computational protocol is utilized. It is found that the intramolecular hydrogen bond N-H···O is responsible for the energetic preference of anti (a) conformer (anti position of 3-fluoroanilino group with respect to the C═C double bond). The Boltzmann ratios of the conformers are related to the differences of the particular dipole moments and/or their dependence on the solvent polarity. The studied acetyl, ethyl ester, and methyl ester substituted fluoroquinolone precursors prefer in the solvent either EZa, ZZa, or both conformers equally, respectively. In order to understand the degree of freedom of rotation of the trans ethyl ester group, B3LYP/6-311G** molecular dynamic simulations were carried out. Vibrational frequencies, electron transitions, as well as NMR spectra are analyzed with respect to conformational analysis, including the effect of the substituent. X-ray structures of the precursors are presented and compared with the results of the conformational analysis.

Palladium-catalysed cyclisation of alkenols: Synthesis of oxaheterocycles as core intermediates of natural compounds.

The study of Pd-catalysed cyclisation reactions of alkenols using different catalytic systems is reported. These transformations affect the stereoselective construction of mono- and/or bicyclic oxaheterocyclic derivatives depending on a starting alkenol. The substrate scope and proposed mechanism of Pd-catalysed cyclisation reactions are also discussed. Moreover, the diastereoselective Pd-catalysed cyclisation of appropriate alkenols to tetrahydrofurans and subsequent cyclisation provided properly substituted 2,5-dioxabicyclo[2.2.1]heptane and 2,6-dioxabicyclo[3.2.1]octane, respectively. Such bicyclic ring subunits are found in many natural products including ocellenynes and aurovertines.

Preparation and spectroscopic, magnetic, and electrochemical studies of mono-/biradical TEMPO derivatives.

A comparison set of mono-/biradical TEMPO derivatives was prepared, novel compounds were fully characterized, and their physicochemical properties were determined. Cyclic voltammetry revealed reversible redox behavior for all studied nitroxides. Moreover, the electron-withdrawing substituents increased the oxidation potential of the respective nitroxides in comparison to electron-donating groups. While EPR spectra of monoradicals in dichloromethane at 295 K reveal the expected three-line signal, spectra of biradicals show more complex features. DFT and MP2 calculations indicate that the EPR splitting pattern of dinitroxide 7 could be explained by its interactions with solvent molecules. In the solid state, mononitroxides 4 and 5 behave as a Heisenberg antiferromagnetic chain, whereas dinitroxides 6-8 are almost isolated paramagnetic diradicals coupled in an antiferromagnetic manner.

(11aS)-1,5,11,11a-Tetra-hydro-1-benzo-thieno[3,2-f]indolizin-3(2H)-one.

The absolute configuration of the title compound, C14H13NOS, was assigned from the synthesis and confirmed by the structure determination. There are two independent mol-ecules in the asymmetric unit. The central six-membered ring of the indolizine moiety adopts an envelope conformation, with the greatest deviations from the mean planes being 0.569 (3) and 0.561 (3) Šfor the indolizine bridgehead C atoms of the two mol-ecules. The benzothieno ring attached to the indolizine ring system is planar to within 0.015 (3) Šin both mol-ecules. In the crystal, weak C-H⋯O and C-H⋯π inter-actions lead to the formation of a three-dimensional framework structure.

N-(2-Chloro-4-nitro-phen-yl)maleamic acid monohydrate.

The title compound, C(10)H(7)ClN(2)O(5)·H(2)O, crystallizes with a half-mol-ecule each of N-(2-chloro-4-nitro-phen-yl)maleamic acid (located on a mirror plane) and water (located on a twofold rotation axis) in the asymmetric unit. The main mol-ecule is planar by symmetry and its conformation is stabilized by an intra-molecular O-H⋯O hydrogen bond. In the crystal, N-H⋯O and O-H⋯O hydrogen bonds link the mol-ecules into a three-dimensional network.

2-Chloro-N-(3-methyl-phen-yl)benzamide.

In the structure of the title compound, C(14)H(12)ClNO, the ortho-Cl atom in the benzoyl ring is positioned syn to the C=O bond, while the meta-methyl group in the aniline ring is positioned anti to the N-H bond. The amide group forms dihedral angles of 60.1 (1) and 22.0 (1)°, respectively, with the benzoyl and aniline rings, while the angle between these rings is 38.7 (1)°. The crystal structure is stabilized by N-H⋯O hydrogen bonds, which give rise to infinite chains running along the c axis.

4-Chloro-N-(3,5-dimethyl-phen-yl)benzamide.

In the mol-ecular structure of the title compound, C(15)H(14)ClNO, the amide group forms dihedral angles of 15.8 (2) and 27.2 (2)°, respectively, with the benzoyl and aniline rings, while the angle between the benzoyl and aniline rings is 11.5 (1)°. The crystal structure is stabilized by N-H⋯O hydrogen bonds, which give rise to infinite chains running along the c axis.

4-Chloro-N-(2,3-dimethyl-phen-yl)benzamide.

In the title compound, C(15)H(14)ClNO, the ortho- and meta-methyl substituents in the aniline ring are anti to the N-H bond. The dihedral angle between the benzoyl and aniline benzene rings is 95.0 (1)°. N-H⋯O hydrogen bonds and C-H⋯π inter-actions link the mol-ecules in the crystal structure.

3-Chloro-N-(2-chloro-phen-yl)benzamide.

In the title compound, C(13)H(9)Cl(2)NO, the meta-Cl atom in the benzoyl ring is positioned anti to the C=O bond, while the ortho-Cl atom in the aniline ring is positioned syn to the N-H bond. The two aromatic rings are almost coplanar, making a dihedral angle of 4.73 (5)°. The crystal structure is stabilized by N-H⋯O hydrogen bonds, which link the mol-ecules into chains along the b axis.

Poly[diamminedi-µ3-dicyanamido-copper(II)].

The asymmetric unit of the title polymeric mononuclear Cu(II) complex, [Cu(C2N3)2(NH3)2] n , contains one half-mol-ecule, the complex being completed through inversion symmetry, with the Cu(II) atom situated on the centre of symmetry. The coordination polyhedron around Cu(II) is a Jahn-Teller-distorted [CuN6] octa-hedron. The terminal N atoms of two dicyanamide ligands and two ammine ligands form an approximate square plane, with N-Cu-N bite angles of 89.72 (5) and 90.28 (5)°. The coordination polyhedron is completed in the axial positions by the central amide-type N atoms of two additional dicyanamide ligands, with an elongated Cu-N distance of 2.548 (1) Å. In turn, each of the four dicyanamide ligands, acting as bidentate, link the Cu(II) ions into a two-dimensional polymeric structure parallel to (100). The ammine H atoms are involved in inter-molecular hydrogen bonding with the free terminal N atoms of neighbouring dicyanamide ligands, yielding a three-dimensional network.

2-Chloro-N-(2,6-dimethyl-phen-yl)benzamide.

In the title compound, C(15)H(14)ClNO, the dihedral angle between the benzoyl and the aniline rings is 3.30 (18)°. In the crystal, N-H⋯O hydrogen bonds link the mol-ecules into chains running along the a axis.