Direct Electron Transfer-Driven Nontoxic Oligomeric Deposition of Sulfonamide Antibiotics onto Carbon Materials for In Situ Water Remediation.

The rising in situ chemical oxidation (ISCO) technologies based on polymerization reactions have advanced the removal of emerging contaminants in the aquatic environment. However, despite their promise, uncertainties persist regarding their effectiveness in eliminating structurally complex contaminants, such as sulfonamide antibiotics (SAs). This study elucidated that oligomerization, rather than mineralization, predominantly governs the removal of SAs in the carbon materials/periodate system. The amine groups in SAs played a crucial role in forming organic radicals and subsequent coupling reactions due to their high f- index and low bond orders. Moreover, the study highlighted the robust adhesion of oligomers to the catalyst surface, facilitated by enhanced van der Waals forces and hydrophobic interactions. Importantly, plant and animal toxicity assessments confirmed the nontoxic nature of oligomers deposited on the carbon material surface, affirming the efficacy of carbon material-based ISCO in treating contaminated surface water and groundwater. Additionally, a novel classification approach, Δlog k, was proposed to differentiate SAs based on their kinetic control steps, providing deeper insights into the quantitative structure-activity relationship (QSAR) and facilitating the selection of optimal descriptors during the oligomerization processes. Overall, these insights significantly enhance our understanding of SAs removal via oligomerization and demonstrate the superiority of C-ISCO based on polymerization in water decontamination.

Withanolides isolated from Tubocapsicum anomalum and their antiproliferative activity.

Seven undescribed withanolides (1-7) and six artificial withanolides (8-13), along with 20 known compounds (14-33) were isolated from the aerial parts of Tubocapsicum anomalum. Their structures were confirmed by comprehensive spectroscopic analyses. The absolute configuration of compound 1 was defined by single-crystal X-ray crystallography. All isolates were evaluated for their antiproliferative effects against five human tumor cell lines (Hep3B, MDA-MB-231, SW480, HCT116 and A549), among which compound 24 (tubocapsanolide A) exhibited the highest activities against the MDA-MB-231 cells with an IC50 value of 1.89 ± 1.03 µM. Further studies showed that 24 exhibited significant damage to mitochondria in MDA-MB-231 cells, including excess reactive oxygen species, decreased mitochondrial membrane potential, and apoptosis initiation. In addition, compound 24 also inhibited cell migration. These findings show that tubocapsanolide A may be a promising molecule for triple-negative breast cancer treatment and merit further evaluation.

Triterpenoids from Anchusa italica and their protective effects on hypoxia/reoxygenation induced cardiomyocytes injury.

Six new triterpenoids (1-6) and 22 known analogues (7-28), were separated from the aerial parts of Anchusa italica Retz., a traditional Uygur medicine for treating cardiovascular and cerebrovascular diseases in the Xinjiang region, China. The possible effects of compounds 1-28 on hypoxia/reoxygenation (H/R) induced cardiomyocytes injury were assayed, and compounds 4, 6-17, 21-22 and 26-28 showed significant protective effects. Further, the representative new compound 6 significantly suppressed the levels of H/R-induced apoptosis and autophagy in neonatal rat cardiomyocytes, with the reversing of the downregulated expression of Bcl-2 and upregulated expression of Bax and Beclin-1 by compound 6 treatment in neonatal rat cardiomyocytes following H/R injury. In addition, compound 6 protected cardiomyocyte from H/R injury, and pretreatment with 6 could decrease CK and LDH levels. Compound 6 also alleviated H/R-induced phosphorylation of p38 MAPK in neonatal rat cardiomyocytes. Therefore, tripterpenoid 6 and its analogues may be the pharmacodyamic material of A. italica, and offer a promising therapeutic approach for treating cardiomyocyte injury induced by H/R.

Identification, characterization and expression profiles of PSEN2 in the Chinese tree shrew (Tupaia belangeri chinensis).

The gene PSEN2 encodes presenilin-2, a subunit of γ-secretase. Mutations in PSEN2 are not only related to Alzheimer's disease but are also involved in other diseases. The Chinese tree shrew (Tupaia belangeri chinensis) is a potential animal model for Alzheimer's disease, although little is known about its cDNA sequence, protein structure, and PSEN2 expression. To better understand PSEN2 in the tree shrew, we cloned this gene by rapid amplification of cDNA ends technology. Hence, we analyzed the sequence and molecular characteristics of PSEN2 mRNA, predicted its spatial structure, and analyzed its expression profiles. We found that tree shrew PSEN2 is 1539 base pairs in length and encodes 330 amino acids. It is homologous and genetically similar to humans (97.64% identity). The protein structure of tree shrew PSEN2 indicated similarities to human PSEN2, both being comprised of numerous transmembrane helices. However, tree shrew PSEN2 possesses seven α-helices, and thus lacks three compared with human PSEN2. Tree shrew PSEN2 mRNAs were ubiquitously detected in all tissues, with a tissue- and temporal-specific pattern. These results pave the way towards the function of tree shrew PSEN2, which will give insights into the mechanisms leading to neurodegenerative and other diseases in humans.

Downregulation of metallothionein 1F, a putative oncosuppressor, by loss of heterozygosity in colon cancer tissue.

PURPOSE: Downregulation of metallothionein (MT) genes has been reported in several tumors with discrepant results. This study is to investigate molecular mechanism of MT gene regulation in colon cancer which is characterized by tumor suppressor gene alterations. EXPERIMENTAL DESIGN: Integral analysis of microarray data with loss of heterozygosity (LOH) information was employed. Quantitative real-time PCR and immunohistochemistry were used to validate MT isoform expression in colon cancer tissues and cell lines. The effects of MT1F expression on RKO cell survival and tumorigenesis was analyzed. Bisulphite sequencing PCR (BSP) and methylation-specific PCR were employed to detect the methylation status of the MT1F gene in colon cancer tissues and cell lines. DNA sequencing was used to examine the LOH at the MT1F locus. RESULTS: MT1F, MT1G, MT1X, and MT2A gene expression was significantly downregulated in colon cancer tissue (p<0.05). Exogenous MT1F expression increased RKO cell apoptosis and inhibited RKO cell migration, invasion and adhesion as well as in vivo tumorigenicity. Downregulation of MT1F gene in majority of human colon tumor tissues is mainly through mechanism by loss of heterozygosity (p=0.001) while CpG island methylation of MT1F gene promoter region was only observed in poorly differentiated, MSI-positive RKO and LoVo colon cancer cell lines. CONCLUSIONS: MT1F is a putative tumor suppressor gene in colon carcinogenesis that is downregulated mainly by LOH in colon cancer tissue. Further studies are required to elucidate a possible role for MT1F downregulation in colon cancer initiation and/or progression.

Synthesis, crystal structure and biological evaluation of a main group seven-coordinated bismuth(III) complex with 2-acetylpyridine N4-phenylthiosemicarbazone.

Up to now, bismuth(III) complexes with thiosemicarbazones have been comparatively rare. Here, a main group seven-coordinated bismuth(III) complex [Bi(L)(NO3)2(CH3CH2OH)] (1) (HL = 2-acetylpyridine N(4)-phenylthiosemicarbazone) has been synthesized and characterized by elemental analysis, IR, (1)H NMR and single-crystal X-ray diffraction studies. The cytotoxicity data suggest that 1 exhibits higher in vitro antiproliferative activity in four human cancer cells tested. Its possible apoptotic mechanism has been evaluated in HepG2 cells. Compound 1 promotes a dose-dependent apoptosis in HepG2 cells and the apoptosis is associated with an increase in intracellular reactive oxygen species (ROS) production and reduction of mitochondrial membrane potential (MMP).

Plasmon-Mediated Photoelectrochemical Hot-Hole Oxidation Coupling Reactions of Adenine on Nanostructured Silver Electrodes.

Surface-enhanced Raman spectroscopy (SERS) has been widely applied in the identification and characterization of DNA structures with high efficiency. Especially, the SERS signals of the adenine group have exhibited high detection sensitivity in several biomolecular systems. However, there is still no unanimous conclusion regarding the interpretation of some special kinds of SERS signals of adenine and its derivatives on silver colloids and electrodes. This Letter presents a new photochemical azo coupling reaction for adenyl residues, in which the adenine is selectively oxidized to (E)-1,2-di(7H-purin-6-yl) diazene (azopurine) in the presence of silver ions, silver colloids, and electrodes of nanostructures under visible light irradiation. The product, azopurine, is first found to be responsible for the SERS signals. This photoelectrochemical oxidative coupling reaction of adenine and its derivatives is promoted by plasmon-mediated hot holes and is regulated by positive potentials and pH of solutions, which opens up new avenues for studying azo coupling in the photoelectrochemistry of adenine-containing biomolecules on electrode surfaces of plasmonic metal nanostructures.

Synthesis, crystal structures, in vitro biological evaluation of zinc(II) and bismuth(III) complexes of 2-acetylpyrazine N(4)-phenylthiosemicarbazone.

Two metal complexes formulated as [Zn(L)(2)](2)·H(2)O (1) and [Bi(L)(NO(3))(2)(CH(3)OH)] (2), where HL=2-acetylpyrazine N(4)-phenylthiosemicarbazone, have been synthesized and characterized by elemental analysis, IR, MS, NMR and single-crystal X-ray diffraction studies. Biological studies, carried out in vitro against selected bacteria and the K562 leukemia cell lines, respectively, have shown that the free ligand and its two complexes may be endowed with important biological properties, especially HL with MIC=3.90 µg/mL against Pseudomonas aeruginosa, the zinc(II) complex 1 with IC(50)=1.0 µM against K562 leukemia cell lines, respectively. The compounds HL and 1 may exert their cytotoxicity activity via induced loss of mitochondria membrane potential (MMP).

A nine-coordinated bismuth(III) complex derived from pentadentate 2,6-diacetylpyridine bis((4)N-methylthiosemicarbazone): crystal structure and both in vitro and in vivo biological evaluation.

Up to now, bismuth(III) complexes with thiosemicarbazones have been comparatively rare. Few in vivo biological studies have been carried out in comparison to the plentiful in vitro data. Here, an interesting nine-coordinated bismuth(III) complex, [Bi(H2L)(NO3)2]NO3 [1; H2L = 2,6-diacetylpyridine bis((4)N-methylthiosemicarbazone)], has been synthesized and structurally characterized. The analytical data reveal the formation of 1:1 (metal/ligand) stoichiometry. In vitro biological studies have indicated that the bismuth complex 1 has shown much higher antibacterial and anticancer activities than its parent ligand, especially with MIC = 10.66 µM against Bacillus cereus and Salmonella typhimurium and IC50 = 26.8 µM against K562 leukemia cells, respectively. More importantly, it also evidently inhibits H22 xenograft tumor growth on tumor-bearing mice (10 mg/kg; inhibitory rate = 61.6%). These results indicate that coordination to bismuth(III) might be an interesting strategy in the discovery of new anticancer drug candidates.

Poly[(µ4-biphenyl-3,3',4,4'-tetracarboxylato)bis[µ2-1,4-bis(imidazol-1-ylmethyl)benzene]dicobalt(II)].

The asymmetric unit of the title two-dimensional coordination polymer, [Co(2)(C(16)H(6)O(8))(C(14)H(14)N(4))(2)](n), contains one Co(2+) ion, half of a biphenyl-3,3',4,4'-tetracarboxylate (bptc) anion lying about an inversion centre and one 1,4-bis(imidazol-1-ylmethyl)benzene (bix) ligand. The Co(II) atom is coordinated by three carboxylate O atoms from two different bptc ligands and two N atoms from two bix ligands constructing a distorted square pyramid. Each Co(2+) ion is interlinked by two bptc anions, while each bptc anion coordinates to four Co atoms as a hexadentate ligand so that four Co(II) atoms and four bptc anions afford a larger 38-membered ring. These inorganic rings are further extended into a two-dimensional undulated network in the (101) plane. Two Co(II) atoms in adjacent 38-membered rings are joined together by pairs of bix ligands forming a 26-membered [Co(2)(bix)(2)] ring that is penetrated by a bptc anion; these components share a common inversion centre.

A three-dimensional framework in 2,2'-biimidazolium bis(2,2'-biimidazole-κ(2)N,N')bis(biphenyl-2,4'-dicarboxylato-κO)manganese(II) hexahydrate.

In the title salt, (C(6)H(8)N(4))[Mn(C(14)H(8)O(4))(2)(C(6)H(6)N(4))(2)]·6H(2)O, the Mn(II) atom lies on an inversion centre and is coordinated by four N atoms from two 2,2'-biimidazole (biim) ligands and two O atoms from two biphenyl-2,4'-dicarboxylate (bpdc) anions to give a slightly distorted octahedral coordination, while the cation lies about another inversion centre. Adjacent [Mn(bpdc)(2)(biim)(2)](2-) anions are linked via two pairs of N-H...O hydrogen bonds, leading to an infinite chain along the [100] direction. The protonated [H(2)biim](2+) moiety acts as a charge-compensating cation and space-filling structural subunit. It bridges two [Mn(bpdc)(2)(biim)(2)](2-) anions through two pairs of N-H...O hydrogen bonds, constructing two R(2)(2)(9) rings, leading to a zigzag chain in the [2-1-1] direction, which gives rise to a ruffled set of [H(2)biim](2+)[Mn(bpdc)(2)(biim)(2)](2-) moieties in the [01-1] plane. The water molecules give rise to a chain structure in which O-H...O hydrogen bonds generate a chain of alternating four- and six-membered water-oxygen R(4)(2)(8) and R(6)(6)(12) rings, each lying about independent inversion centres giving rise to a chain along the [100] direction. Within the water chain, the (H(2)O)(6) water rings are hydrogen bonded to two O atoms from two [Mn(bpdc)(2)(biim)(2)](2-) anions, giving rise to a three-dimensional framework.

Natural Products and Derivatives Targeting at Cancer Energy Metabolism: A Potential Treatment Strategy.

In the 1920s, Dr Otto Warburg first suggested the significant difference in energy metabolism between malignant cancer cells and adjacent normal cells. Tumor cells mainly adopt the glycolysis as energy source to maintain tumor cell growth and biosynthesis under aerobic conditions. Investigation on energy metabolism pathway in cancer cells has aroused the interest of cancer researchers all around the world. In recent years, plentiful studies suggest that targeting the peculiar cancer energy metabolic pathways, including glycolysis, mitochondrial respiration, amino acid metabolism, and fatty acid oxidation may be an effective strategy to starve cancer cells by blocking essential nutrients. Natural products (NPs) are considered as the "treasure trove of small molecules drugs" and have played an extremely remarkable role in the discovery and development of anticancer drugs. And numerous NPs have been reported to act on cancer energy metabolism targets. Herein, a comprehensive overview about cancer energy metabolism targets and their natural-occurring inhibitors is prepared.

Cytotoxicity and structure-activity relationships of four alpha-N-heterocyclic thiosemicarbazone derivatives crystal structure of 2-acetylpyrazine thiosemicarbazone.

A series of thiosemicarbazone ligands, HL(1) (2-acetylpyrazine thiosemicarbazone), HL(2) (2-acetylpyrazine N(4)-methylthiosemicarbazone), HL(3) (2-benzoylpyridine thiosemicarbazone) and HL(4) (2-benzoylpyridine N(4)-methylthiosemicarbazone), have been synthesized. The crystal structure of HL(1) has been determined by single-crystal X-ray diffraction. Hydrogen bonds link the different components to stabilize the crystal structure. The antitumor activity of the four ligands were tested against K562 leucocythemia and BEL7402 liver cancer cell lines. All the thiosemicarbazones showed significant antitumor activity. Different substituents on the ligands show different levels of antitumor activity. By comparison with the other thiosemicarbazone species studied, HL(4) with substitution at N(4) position in thiosemicarbazone along with 2-benzoylpyridine is the most active thiosemicarbazone ligand with IC(50)=0.002microm in the K562 leucocythemia cell line and 0.138microm in the BEL7402 liver cancer cell line, respectively.

Tin thiocarbonohydrazone complexes: synthesis, crystal structures and biological evaluation.

In this article, three organotin complexes formulated as [(Me)2Sn(H2L1)] (1), [(Ph)2Sn(H2L1)]·MeOH (2) and [(Me)2Sn(HL2)(OAc)]4(Me)2O (3) (H4L1 = bis(2-hydroxybenzaldehyde) thiocarbohydrazone and H2L2 = bis(2-acetylpyrazine) thiocarbonohydrazone) have been synthesized and structurally characterized. Growth inhibition assays indicated that both the proligands and the three complexes are capable of showing anticancer activity against the human hepatocellular carcinoma HepG2 cells with H2L2 and complex 3 showing much higher cytotoxic potential. Subsequent toxicity studies on normal QSG7701cells showed that complex 3 has the highest tumor cell selectivity, and its IC50 value on QSG7701 cells is 8.48 fold higher than that in HepG2 cells. In acute toxicity experiments, complex 3 produces a dose-dependent effect in NIH mice with a LD50 value of 17.2 mg kg-1.

Less toxic zinc(ii), diorganotin(iv), gallium(iii) and cadmium(ii) complexes derived from 2-benzoylpyridine N,N-dimethylthiosemicarbazone: synthesis, crystal structures, cytotoxicity and investigations of mechanisms of action.

Four metal complexes based on 2-benzoylpyridine N,N-dimethylthiosemicarbazone (Bp44mT) were designed. Free ligand and zinc(ii), diorganotin(iv), gallium(iii) and cadmium(ii) complexes all demonstrated pronounced activity, which was indicated using the growth inhibition test in vitro. Interestingly, most of the compounds were found to be selective against hepatocellular carcinoma (HepG2) cells but had little effect on normal hepatocyte (QSG7701) cells. In particular, Zn(Bp44mT)2 (1) exhibited toxicity on QSG7701 cells which approximately 12-fold lower than that on HepG2 cells. The studies of mechanisms of action indicated that 1 induced reactive oxygen species (ROS) generation in a dose-dependent manner via the mitochondria transduction pathway. Protein analyses showed that 1 significantly promoted p21 and p53 gene expression, causing caspase-3 activation.

Bis(2,2'-bipyridyl-κN,N')(carbonato-κO,O')cobalt(III) bromide trihydrate.

The title complex, [Co(CO(3))(C(10)H(8)N(2))(2)]Br·3H(2)O, is isostructural with the chloride analogue. The six-coordinated octahedral [Co(2,2'-bipy)(2)CO(3)](+) cation (2,2'-bipy is 2,2'-bipyrid-yl), bromide ion and water mol-ecules are linked together via O-H⋯Br and O-H⋯O hydrogen bonds, generating a one-dimensional chain.

N'-Ferrocenyl-2-hydroxy-benzohydrazide.

The title complex, [Fe(C(5)H(5))(C(13)H(11)N(2)O(3))], was prepared via self-assembly using ferrocenyl hydrazide and ethyl salicylate. The compound is potentially a tridentate ferrocene-based ligand. The conformation of the mol-ecule allows the formation of an intra-molecular N-H⋯O hydrogen bond involving the hydroxyl group. The CONHNHCO unit and the rings bonded to it are nearly coplanar. The crystal structure is stabilized by inter-molecular O-H⋯O(carbon-yl) and N-H⋯O(carbon-yl) hydrogen bonds.

2-Acetyl-pyrazine 4-methyl-thio-semi-carbazone.

The title compound, C(8)H(11)N(5)S, has been prepared by the reaction of 2-acetyl-pyrazine with 4-methyl-3-thio-semi-carbazide. It exists in the thione form and adopts the E configuration. The mol-ecules are connected by the inter-molecular N-H⋯N and N-H⋯S inter-actions.

Cu(ii), Ga(iii) and In(iii) complexes of 2-acetylpyridine N(4)-phenylthiosemicarbazone: synthesis, spectral characterization and biological activities.

In this paper, synthesis and characterization of metal complexes [Cu2(L)3]ClO4 (1), [Ga(L)2]NO3·2H2O (2) and [In(L)2]NO3·H2O (3) (HL = 2-acetylpyridine N(4)-phenylthiosemicarbazone) was carried out, including elemental analysis, spectral analysis (IR, UV-vis, NMR), and X-ray crystallography. Complex 1 contains one S-bridged binuclear [Cu2(L)3]+ unit, where two Cu atoms display diverse coordination geometries: one being square planar geometry and the other octahedral geometry. Both 2 and 3 are mononuclear complexes, and the metal centers in 2 and 3 are chelated by two NNS tridentate ligands possessing a distorted octahedral geometry. Biological studies show that all the complexes possess a wide spectrum of modest to effective antibacterial activities and remarkable cytotoxicities against HepG2 cells, and 1, in particular, with an IC50 value of 0.19 ± 0.06 µM, is 113-fold and 28-fold more cytotoxic than HL and the antitumor drug mitoxantrone, respectively. In addition, 3 exhibits excellent photoluminescence properties. Upon the addition of 1 equiv of In3+ ions, a remarkable fluorescence intensity of HL and fluorescent color change (from transparent to light-green) could be observed with 365 nm light, indicating that this ligand may be used as a promising colorimetric and fluorescent probe for In3+ detection.

Theoretical study of the spectroscopic and nonlinear optical properties of trans- and cis-4-hydroxyazobenzene.

We investigate the molecular structure, vibrational and electronic absorption spectra, and electronic hyperpolarizabilities of trans and cis isomers of 4-hydroxyazobenzene (HOAB) via density functional theory. Results show that the azo dye exhibits a high third-order nonlinear optical response and good optical transparency. Both the basis set and the functional are important influences on the results obtained when calculating the absorption spectrum and NLO response. We also study the effect of the solvent on the electronic absorption spectrum to assess the ability of the functional to reproduce the experimental spectrum in combination with a suitable solvent model. Our calculations show that the SMD model of Truhlar et al. handles the electrostatic and the non-electrostatic effects of hydrogen-bonding solvents on the absorption spectrum better than the traditional polarizable continuum model does. In addition, our results indicate that the dye trans-HOAB exhibits a high second hyperpolarizability and excellent optical transparency. Also, although the second hyperpolarizability of cis-HOAB is much lower than that of trans-HOAB, it is non-negligible when calculating the optical nonlinearity of HOAB under an optical pump. We also examine the effect of frequency dispersion on second harmonic generation. This study provides the basis for further research on the spectroscopic and nonlinear optical properties of novel azo dyes and other π-conjugated compounds.