Chloro Derivatives Research Articles

Molecular structures of 2-hydroxy-1,4-naphthoqinone derivatives and their zinc(II) complexes: Combining experiment and density functional theory

Molecular structures of 2-hydroxy-1,4-naphthoquinone (Lw), its chloro (ClLw; 2-chloro-3-hydroxy-1,4-naphthoquinone) and bromo (BrLw; 2-bromo-3-hydroxy-1,4-naphthoquinone) derivatives and their Zn(II) complexes are derived from the wB97x based density functional theory. The calculations predicted that the trans, trans conformer of the Zn(II) complex of 2-hydroxy-1,4-naphthoquinone (ZnLw) turns out to be of the lowest energy. A comparison of C(2) substituted chloro and bromo derivatives has been presented. Single X-ray crystal structure revealed that the BrLw belongs to monoclinic Cc space group with three independent molecules in its asymmetric unit cell with the crystal network extending through π–π stacking whilst the ZnBrLw complex possesses monoclinic P21/n space group and facilitate hydrogen bonding interactions. Electrochemical characterization describing the redox behavior of BrLw and Zn(II) complex in DMSO has been carried out through cyclic voltammetry experiments.

Detection and characterization of clostebol sulfate metabolites in Caucasian population.

Anabolic androgenic steroids (AAS) are synthetic testosterone derivatives which undergo extensive metabolism in man. Differences in the excretion of phase II metabolites are strongly associated with inter-individual and inter-ethnic variations. Sulfate metabolites have been described as long-term metabolites for some AAS. Clostebol is the 4-chloro derivative of testosterone and the aim of the present study was the evaluation of clostebol sulfate metabolites in Caucasian population by LC-MS/MS technology. Clostebol was orally administered to four healthy Caucasian male volunteers, and excretion study urines were collected up to 31 days. Several analytical strategies (neutral loss scan, precursor ion scan and selected reaction monitoring acquisitions modes) were applied to detect sulfate metabolites in post-administration samples. Sixteen sulfate metabolites were detected, five of them having detectability times above 10 days (S1a, S2a, S3b, S3g and S4b). Interestingly, metabolite S1a could be detected up to the last collected sample of all excretion studies and it was characterized by LC-MS/MS and GC-MS as 4ξ-chloro-5α-androst-3β-ol-17-one 3β-sulfate. Thus, monitoring of S1a improves the detection time of clostebol misuse with respect to the commonly monitored metabolites, excreted in the glucuronide fraction. Importantly, this new metabolite can be incorporated into recently developed LC-MS/MS screening methods base on the direct detection of phase II metabolites.

Synthetic Approaches to Aryl Halomethyl Sulfones

Aryl halomethyl sulfones are halogenated organosulfur compounds which continuously draw attention owing to their bioactivity as well as wide applications in organic synthesis. This review summarizes the methods for their preparation, describing the reported routes to fluoro, chloro, bromo and iodo derivatives. Their synthetic and biological applications are also highlighted. Keywords: Sulfones, sulfonyl group, organosulfur compounds, halogen, halomethyl group, halogenation, biocides.

New Isolated-Pentagon-Rule and Skeletally Transformed Isomers of C100 Fullerene Identified by Structure Elucidation of their Chloro Derivatives.

High-temperature chlorination of C100 fullerene followed by X-ray structure determination of the chloro derivatives enabled the identification of three isomers of C100 from the fullerene soot, specifically numbers 18, 425, and 417, which obey the isolated pentagon rule (IPR). Among them, isomers C1-C100 (425) and C2-C100 (18) afforded C1-C100 (425)Cl22 and C2-C100 (18)Cl28/30 compounds, respectively, which retain their IPR cage connectivities. In contrast, isomer C2v -C100 (417) gives Cs -C100 (417)Cl28 which undergoes a skeletal transformation by the loss of a C2 fragment, resulting in the formation of a nonclassical (NC) C1-C98 (NC)Cl26 with a heptagon in the carbon cage. Most probably, two nonclassical C1-C100 (NC)Cl18/22 chloro derivatives originate from the IPR isomer C1-C100 (382), although both C1-C100 (344) and even nonclassical C1-C100 (NC) can be also considered as the starting isomers.

New Isolated‐Pentagon‐Rule and Skeletally Transformed Isomers of C100 Fullerene Identified by Structure Elucidation of their Chloro Derivatives

AbstractHigh‐temperature chlorination of C100 fullerene followed by X‐ray structure determination of the chloro derivatives enabled the identification of three isomers of C100 from the fullerene soot, specifically numbers 18, 425, and 417, which obey the isolated pentagon rule (IPR). Among them, isomers C1‐C100(425) and C2‐C100(18) afforded C1‐C100(425)Cl22 and C2‐C100(18)Cl28/30 compounds, respectively, which retain their IPR cage connectivities. In contrast, isomer C2v‐C100(417) gives Cs‐C100(417)Cl28 which undergoes a skeletal transformation by the loss of a C2 fragment, resulting in the formation of a nonclassical (NC) C1‐C98(NC)Cl26 with a heptagon in the carbon cage. Most probably, two nonclassical C1‐C100(NC)Cl18/22 chloro derivatives originate from the IPR isomer C1‐C100(382), although both C1‐C100(344) and even nonclassical C1‐C100(NC) can be also considered as the starting isomers.

1,2,4‐Triazole‐based N‐heterocyclic carbene complexes of gold(I): synthesis, characterization and biological activity

Two gold(I) complexes of the (NHC)AuX type bearing a triazole‐based N‐heterocyclic carbene (NHC) ligand (1‐tert‐butyl‐4‐(4‐methylphenyl)‐3‐phenyl‐1H‐1,2,4‐triazol‐4‐ium‐5‐ylidene) and various halide ligands (X = Br, I) were synthesized and characterized in solution using NMR spectroscopy as well as in the solid state using X‐ray diffraction techniques. The cytotoxic properties of both compounds and the precursor, (NHC)AuCl, were screened against a panel of human tumour cell lines including liver cancer (HepG2), cervical cancer (HeLa S3) and leukaemia (CCRF‐CEM, HL‐60) and compared to cisplatin and auranofin. It was found that the activities of the chloro and bromo derivatives were generally superior to that of cisplatin and slightly less effective compared to auranofin, except for HepG2 cells where auranofin was not as effective. In addition, the ability to induce membrane phosphatidyl serine externalization as a hallmark of apoptosis in CCRF‐CEM leukaemic cells was investigated. Copyright © 2016 John Wiley & Sons, Ltd.

Aluminium, gallium and indium complexes supported by a chiral phenolato-prolinolato dianionic ligand

AbstractCongeneric complexes (

The Preparation and Spectroscopic Characterization of Chloroalkyl- and Chlorobenzyl-Aminobis(Methylenephosphonic Acids)

GRAPHICAL ABSTRACT

Palladium–benzodiazepine derivatives as promising metallodrugs for the development of antiepileptic therapies

We synthesized two organometallic diazepam–palladium(II) derivatives by C–H activation of diazepam (DZP) with palladium salts, i.e., PdCl2 and Pd(OAc)2 (OAc=acetate). Both compounds obtained are air stable and were isolated in good yields. The anticonvulsant potential of the complexes, labeled [(DZP)PdCl]2 and [(DZP)PdOAc]2, was evaluated through two animal models: pentylenetetrazole (PTZ)- and picrotoxin (PTX)-induced convulsions. The organometallic DZP–palladium(II) acetate complex, [(DZP)PdOAc]2, significantly increased (p<0.01 or p<0.001) latencies and protected the animals against convulsions induced by PTZ and PTX, while the analogous chloro derivative, [(DZP)PdCl]2, was effective (p<0.01) only in the PTZ model. These effects appear to be mediated through the GABAergic system. The possible mechanism of action of the DZP–palladium(II) complexes was also confirmed with the use of flumazenil (FLU), a GABAA-benzodiazepine receptor complex site antagonist. Herein, we present the first report of the anticonvulsant properties of organometallic DZP–palladium(II) complexes as well as evidence that these compounds may play an important role in the study of new drugs to treat patients with epilepsy.

Gas phase enthalpies of formation, isomerization, and disproportionation of mono- through tetra-substituted tetrahedranes: A G4(MP2)/G4 theoretical study

Gas phase standard state (298.15K, 1atm) enthalpies of formation (ΔfH°(g)), enthalpies of disproportionation to two corresponding acetylene molecules (ΔrxnH°(g),Td→acet), and enthalpies of isomerization from a tetrahedrane geometry to a 1,3-cyclobutadiene structure (ΔisomH°(g),Td→CBD) were calculated for the mono- through tetra-substituted hydro, fluoro, chloro, bromo, methyl, ethynyl, and cyano carbon tetrahedrane derivatives at the G4(MP2) and G4 levels of theory. All derivatives have endothermic ΔfH°(g) indicative of the cage strain in these systems. In all cases, ΔrxnH°(g),Td→acet and ΔisomH°(g),Td→CBD are predicted to be substantially exothermic. High quality linear regression fits within a homologous series were obtained between the number of substituents and the G4(MP2)/G4 estimated ΔfH°(g). Via calculations on lower homolog members, this strategy was employed to allow extrapolated G4 and/or G4(MP2) ΔfH°(g) (as well as some ΔrxnH°(g),Td→acet and ΔisomH°(g),Td→CBD) to be obtained for the higher homolog t-butyl, trifluoromethyl, and trimethylsilyl carbon tetrahedrane derivatives.

Synthesis, Characterization, Antimicrobial Screening and Free-Radical Scavenging Activity of Some Novel Substituted Pyrazoles.

The present work deals with the synthesis of acetoxysulfonamide pyrazole derivatives, substituted 4,5-dihydropyrazole-1-carbothioamide and 4,5-dihydropyrazole-1-isonicotinoyl derivatives starting from substituted vanillin chalcones. Acetoxysulfonamide pyrazole derivatives were prepared from the reaction of chalcones with p-sulfamylphenylhydrazine followed by treatment with acetic anhydride. At the same time 4,5-dihydropyrazole-1-carbothioamide and 4,5-dihydropyrazole-1-isonicotinoyl derivatives were prepared from the reaction of chalcones with either thiosemicarbazide or isonicotinic acid hydrazide, respectively. The synthesized compounds were structurally characterized on the basis of IR, 1H-NMR, 13C-NMR spectral data and microanalyses. All of the newly isolated compounds were tested for their antimicrobial activities. The antimicrobial screening using the agar well-diffusion method revealed that the chloro derivatives are the most active ones. Moreover, the antioxidant and anti-inflammatory activity of these chloro derivatives are also studied using the DPPH radical scavenging and NO radical scavenging methods, respectively.

Tunable Electrochemical and Catalytic Features of BIAN- and BIAO-Derived Ruthenium Complexes.

This article deals with a class of ruthenium-BIAN-derived complexes, [Ru(II)(tpm)(R-BIAN)Cl]ClO4 (tpm = tris(1-pyrazolyl)methane, R-BIAN = bis(arylimino)acenaphthene, R = 4-OMe ([1a]ClO4), 4-F ([1b]ClO4), 4-Cl ([1c]ClO4), 4-NO2 ([1d]ClO4)) and [Ru(II)(tpm)(OMe-BIAN)H2O](2+) ([3a](ClO4)2). The R-BIAN framework with R = H, however, leads to the selective formation of partially hydrolyzed BIAO ([N-(phenyl)imino]acenapthenone)-derived complex [Ru(II)(tpm)(BIAO)Cl]ClO4 ([2]ClO4). The redox-sensitive bond parameters involving -N═C-C═N- or -N═C-C═O of BIAN or BIAO in the crystals of representative [1a]ClO4, [3a](PF6)2, or [2]ClO4 establish its unreduced form. The chloro derivatives 1a(+)-1d(+) and 2(+) exhibit one oxidation and successive reduction processes in CH3CN within the potential limit of ±2.0 V versus SCE, and the redox potentials follow the order 1a(+) < 1b(+) < 1c(+) < 1d(+) ≈ 2(+). The electronic structural aspects of 1a(n)-1d(n) and 2(n) (n = +2, +1, 0, -1, -2, -3) have been assessed by UV-vis and EPR spectroelectrochemistry, DFT-calculated MO compositions, and Mulliken spin density distributions in paramagnetic intermediate states which reveal metal-based (Ru(II) → Ru(III)) oxidation and primarily BIAN- or BIAO-based successive reduction processes. The aqua complex 3a(2+) undergoes two proton-coupled redox processes at 0.56 and 0.85 V versus SCE in phosphate buffer (pH 7) corresponding to {Ru(II)-H2O}/{Ru(III)-OH} and {Ru(III)-OH}/{Ru(IV)═O}, respectively. The chloro (1a(+)-1d(+)) and aqua (3a(2+)) derivatives are found to be equally active in functioning as efficient precatalysts toward the epoxidation of a wide variety of alkenes in the presence of PhI(OAc)2 as oxidant in CH2Cl2 at 298 K, though the analogous 2(+) remains virtually inactive. The detailed experimental analysis with the representative precatalyst 1a(+) suggests the involvement of the active {Ru(IV)═O} species in the catalytic cycle, and the reaction proceeds through the radical mechanism, as also supported by the DFT calculations.

English

A series of benzimidazole derivatives (5a-c) were synthesized by coupling 5-substituted 2-chloromethyl benzimidazole (3a-c) with 2-mercapto-N-methyl imidazole. The synthesized compounds were characterized by infra-red (IR), nuclear magnetic resonance (NMR) and elemental analyses. Further, the synthesized compounds were tested on plantlet production from protocorm like bodies (PLBs) sections of Oncidium. PLBs sections were cultured on half strength modified Murashige and Skoogs (MS) medium alone and also modified MS medium supplemented with the synthesized chloro, methyl and nitro derivatives individually at 2 or 5 µM concentrations. Among these three compounds, PLBs sections cultured on medium supplemented with nitro compound (5c) at 5 µM concentration produced maximum number (95) of plantlets. Key words: Benzimidazole derivatives, protocorm like bodies, plant growth regulators, 2-mercapto-N-methyl imidazole.

ChemInform Abstract: Copper‐Catalyzed Intramolecular O‐Arylation: A Simple and Efficient Method for Benzoxazole Synthesis.

AbstractA wide range of 2‐substituted benzoxazoles is synthesized from N‐(2‐halophenyl)benzamides including less reactive chloro derivatives via Cu‐catalyzed intramolecular coupling reactions using 2‐methoxybenzoate as the ligand.

Antitumour and antimicrobial activities of chloro derivatives of Synthetic Curcumin and their metal chelates.

Curcumin and its analogues have been extensively studied as effective medicine for the treatment of cancer and related diseases. Recently several curcuminoid analogues were synthesized and their chemotherapeutic potential has been revealed. In the present study, the synthesis and characterization of three new chlorine containing curcuminoid analogues and their metal chelates Cu(II) and Al(III) are discussed here. The curcuminoid analogues namely 1,7-di(4-chloro phenyl)-1,6-heptadiene-3,5-dione(HL1), 1,7- di(2-chloro phenyl)-1,6-heptadiene-3,5-dione(HL2), and 1,7-bis(3,4 dichloro phenyl)-1,6-heptadiene-3,5-dione(HL3) and their Cu(II) and Al(III) chelates were synthesized and were characterized using UV, IR, 1H NMR and mass spectral data. In vitro cytotoxic studis were done with ligand and metal complexes (Cu & Al) against DLA and EAC cells using Tryptan blue exclusion method and antibacterial study of the compounds were done using agar well diffusion method. The in vivo antitumour activity of the ligand and complexes were determined by using DLA cells in mice and compared with standard anticancer drug cyclophosphamide. The life span of the treated animals were increased upto 60-70%. The present investigation reveals that the Cu(II) complexes show enhanced cytotoxic activity where as the Al(III) complexes have greater activity towards in vivo antitumour studies and antibacterial studies.

Ligand cooperation in the formal hydrogenation of N2O using a PC(sp2)P iridium pincer complex.

A new PC(carbene)P pincer ligand with 2,3-benzo[b]thiophene linkers connecting the flanking dialkyl phosphine donors to the central carbene can be attached to Ir(I). The chloro derivative reacts with N2O with loss of N2 to form an iridaepoxide species by addition of an oxygen atom to the Ir═C linkage. This compound reacts with H2 to afford the oxidative addition product, in which the hydride ligands are trans to the Ir-O bond. Heating this dihydride results in slow release of H2O; kinetic and spectroscopic studies show that conversion of the dihydride to its isomer, in which the hydrides are cis to the Ir-O bond, is required for H2O elimination to take place. Together, these reactions constitute the stoichiometric conversion of N2O and H2 to N2 and H2O; further mechanistic studies suggest ways to make the system catalytic.

Chalcone derivatives as potential antifungal agents: Synthesis, and antifungal activity.

Much research has been carried out with the aim to discover the therapeutic values of chalcone derivatives. Chalcones possess wide range of pharmacological activity such as antibacterial, antimalarial, antiprotozoal, antitubercular, anticancer, and antifungal agents etc. The presence of reactive α,β-unsaturated keto group in chalcones is found to be responsible for their biological activity. The rapid developments of resistance to antifungal agents, led to design, and synthesize the new antifungal agents. The derivatives of chalcones were prepared using Claisen–Schmidt condensation scheme with appropriate tetralone and aldehyde derivatives. Ten derivatives were synthesized and were biologically screened for antifungal activity. The newly synthesized derivatives of chalcone showed antifungal activity against fungal species, Microsporum gypseum. The results so obtained were superior or comparable to ketoconazole. It was observed that none of the compounds tested showed positive results for fungi Candida albicans nor against fungi Aspergillus niger. Chalcone derivatives showed inhibitory effect against M. gypseum species of fungus. It was found that among the chalcone derivatives so synthesized, two of them, that is, 4-chloro derivative, and unsubstituted derivative of chalcone showed antifungal activity superior to ketoconazole. Thus, these can be the potential new molecule as antifungal agent.

Halogen and Hydrogen Bonding Benzothiophene Diol Derivatives: A Study Using ab initio Calculations and X-Ray Crystal Structure Measurements.

The aim of this study is to describe and compare the supramolecular interactions, in the solid state, of chloro-, bromo-, and iodobenzothiophene diols. The compounds were obtained through organo-catalyzed reactions starting from 3-substituted halobenzothiophene carbaldehydes. Energies of the noncovalent interactions were obtained by density functional theory calculations. Bond distances and angles were found to be in accordance with those determined by X-ray structure analysis. anti-Bromobenzothiophene derivatives showed strong halogen⋅⋅⋅π interactions between bromine and the heterocyclic phenyl ring, corresponding to an energy of 7.5 kcal mol−1. syn-Bromo and syn-iodo derivatives appeared to be isostructural, showing X⋅⋅⋅O (carbonyl) interactions, π stacking, and formation of extended hydrogen bonding networks. In contrast, the chloro derivatives displayed no halogen bonding interactions.

Crystal structure of 1,6-di-thia-cyclo-deca-cis-3,cis-8-diene (DTCDD).

The title compound, C8H12S2 (trivial name DTCDD), was obtained as a side product of the reaction between cis-1,4-di­chloro­but-2-ene and sodium sulfide. The asymmetric unit consists of one-quarter of the mol­ecule (S site symmetry 2) and the complete mol­ecule has 2/m (C 2h) point symmetry with the C=C bond in an E conformation. The geometry of the title compound is compared to those of a chloro derivative and a mercury complex.

Molecular dynamics simulation of halogen bonding mimics experimental data for cathepsin L inhibition.

A MD simulation protocol was developed to model halogen bonding in protein-ligand complexes by inclusion of a charged extra point to represent the anisotropic distribution of charge on the halogen atom. This protocol was then used to simulate the interactions of cathepsin L with a series of halogenated and non-halogenated inhibitors. Our results show that chloro, bromo and iodo derivatives have progressively narrower distributions of calculated geometries, which reflects the order of affinity I > Br > Cl, in agreement with the IC50 values. Graphs for the Cl, Br and I analogs show stable interactions between the halogen atom and the Gly61 carbonyl oxygen of the enzyme. The halogen-oxygen distance is close to or less than the sum of the van der Waals radii; the C-X···O angle is about 170°; and the X···O=C angle approaches 120°, as expected for halogen bond formation. In the case of the iodo-substituted analogs, these effects are enhanced by introduction of a fluorine atom on the inhibitors' halogen-bonding phenyl ring, indicating that the electron withdrawing group enlarges the σ-hole, resulting in improved halogen bonding properties.