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The reaction between the (R,S)-fixolide 4-methyl­thio­semicarbazone and PdII chloride yielded the title compound, [Pd(C20H30N3S)2]·C2H6O {common name: trans-bis­[(R,S)-fixolide 4-methyl­thio­semicarbazonato-κ²N²S]palladium(II) ethanol monosolvate}. The asymmetric unit of the title compound consists of one bis-thio­semicarbazonato PdII complex and one ethanol solvent mol­ecule. The thio­semicarbazononato ligands act as metal chelators with a trans configuration in a distorted square-planar geometry. A C—HS intra­molecular inter­action, with graph-set motif S(6), is observed and the coordination sphere resembles a hydrogen-bonded macrocyclic environment. Additionally, one C—HPd anagostic inter­action can be suggested. Each ligand is disordered over the aliphatic ring, which adopts a half-chair conformation, and two methyl groups [s.o.f. = 0.624 (2):0.376 (2)]. The disorder includes the chiral carbon atoms and, remarkably, one ligand has the (R)-isomer with the highest s.o.f. value atoms, while the other one shows the opposite, the atoms with the highest s.o.f. value are associated with the (S)-isomer. The N—N—C(=S)—N fragments of the ligands are approximately planar, with the maximum deviations from the mean plane through the selected atoms being 0.0567 (1) and −0.0307 (8) Å (r.m.s.d. = 0.0403 and 0.0269 Å) and the dihedral angle with the respective aromatic rings amount to 46.68 (5) and 50.66 (4)°. In the crystal, the complexes are linked via pairs of N—HS inter­actions, with graph-set motif R2²(8), into centrosymmetric dimers. The dimers are further connected by centrosymmetric pairs of ethanol mol­ecules, building mono-periodic hydrogen-bonded ribbons along [011]. The Hirshfeld surface analysis indicates that the major contributions for the crystal cohesion are [atoms with highest/lowest s.o.f.s considered separately]: HH (81.6/82.0%), HC/CH (6.5/6.4%), HN/NH (5.2/5.0%) and HS/SH (5.0/4.9%). [ABSTRACT FROM AUTHOR]

The equimolar and hydro-chloric acid-catalysed reaction between cis -jasmone and 4-methyl-thio-semicarbazide in ethano-lic solution yields the title compound, C 13 H 21 N 3 S (common name: cis -jasmone 4-methyl-thio-semicarbazone). Two mol-ecules with all atoms in general positions are present in the asymmetric unit. In one of them, the carbon chain is disordered [site occupancy ratio = 0.821 (3):0.179 (3)]. The thio-semicarbazone entities [N-N-C(=S)-N] are approximately planar, with the maximum deviation from the mean plane through the selected atoms being -0.0115 (16) Å (r.m.s.d. = 0.0078 Å) for the non-disordered mol-ecule and 0.0052 (14) Å (r.m.s.d. = 0.0031 Å) for the disordered one. The mol-ecules are not planar, since the jasmone groups have a chain with sp 3 -hybridized carbon atoms and, in addition, the thio-semicarbazone fragments are attached to the respective carbon five-membered rings and the dihedral angles between them for each mol-ecule amount to 8.9 (1) and 6.3 (1)°. In the crystal, the mol-ecules are connected through pairs of N-H⋯S and C-H⋯S inter-actions into crystallographically independent centrosymmetric dimers, in which rings of graph-set motifs R 2 2 (8) and R 2 1 (7) are observed. A Hirshfeld surface analysis indicates that the major contributions for the crystal cohesion are from H⋯H (70.6%), H⋯S/S⋯H (16.7%), H⋯C/C⋯H (7.5%) and H⋯N/N⋯H (4.9%) inter-actions [considering the two crystallographically independent mol-ecules and only the disordered atoms with the highest s.o.f. for the evaluation]., (© Oliveira et al. 2024.)

A second crystalline modification of the title compound, C 12 H 19 N 3 S [common name: cis -jasmone thio-semicarbazone] was crystallized from tetra-hydro-furane at room temperature. There is one crystallographic independent mol-ecule in the asymmetric unit, showing disorder in the cis -jasmone chain [site-occupancy ratio = 0.590 (14):0.410 (14)]. The thio-semicarbazone entity is approximately planar, with the maximum deviation from the mean plane through the N/N/C/S/N atoms being 0.0463 (14) Å [r.m.s.d. = 0.0324 Å], while for the five-membered ring of the jasmone fragment, the maximum deviation from the mean plane through the carbon atoms amounts to 0.0465 (15) Å [r.m.s.d. = 0.0338 Å]. The mol-ecule is not planar due to the dihedral angle between these two fragments, which is 8.93 (1)°, and due to the sp 3 -hybridized carbon atoms in the jasmone fragment chain. In the crystal, the mol-ecules are connected by N-H⋯S and C-H⋯S inter-actions, with graph-set motifs R 2 2 (8) and R 2 1 (7), building mono-periodic hydrogen-bonded ribbons along [010]. A Hirshfeld surface analysis indicates that the major contributions for the crystal cohesion are H⋯H (67.8%), H⋯S/S⋯H (15.0%), H⋯C/C⋯H (8.5%) and H⋯N/N⋯H (5.6%) [only non-disordered atoms and those with the highest s.o.f. were considered]. This work reports the second crystalline modification of the cis -jasmone thio-semicarbazone structure, the first one being published recently [Orsoni et al. (2020 ▸). Int. J. Mol. Sci. 21 , 8681-8697] with the crystals obtained in ethanol at 273 K., (© Oliveira et al. 2023.)

The reaction between a racemic mixture of ( R , S )-fixolide and 4-methyl-thio-semicarbazide in ethanol with a 1:1 stoichiometric ratio and catalysed with HCl, yielded the title compound, C 20 H 31 N 3 S [common name: ( R , S )-fixolide 4-methyl-thio-semicarbazone]. There is one crystallographically independent mol-ecule in the asymmetric unit, which is disordered over the aliphatic ring [site-occupancy ratio = 0.667 (13):0.333 (13)]. The disorder includes the chiral C atom, the neighbouring methyl-ene group and the methyl H atoms of the methyl group bonded to the chiral C atom. The maximum deviations from the mean plane through the disordered aliphatic ring amount to 0.328 (6) and -0.334 (6) Å [r.m.s.d. = 0.2061 Å], and -0.3677 (12) and 0.3380 (12) Å [r.m.s.d. = 0.2198 Å] for the two different sites. Both fragments show a half-chair conformation. Additionally, the N-N-C(=S)-N entity is approximately planar, with the maximum deviation from the mean plane through the selected atoms being 0.0135 (18) Å [r.m.s.d. = 0.0100 Å]. The mol-ecule is not planar due to the dihedral angle between the thio-semicarbazone entity and the aromatic ring, which amounts to 51.8 (1)°, and due to the sp 3 -hybridized carbon atoms of the fixolide fragment. In the crystal, the mol-ecules are connected by H⋯S inter-actions with graph-set motif C (4), forming a mono-periodic hydrogen-bonded ribbon along [100]. The Hirshfeld surface analysis suggests that the major contributions for the crystal cohesion are [( R , S )-isomers considered separately] H⋯H (75.7%), H⋯S/S⋯H (11.6%), H⋯C/C⋯H (8.3% and H⋯N/N⋯H (4.4% for both of them)., (© Melo et al. 2023.)

The hydro-chloric acid-catalyzed equimolar reaction between cis -jasmone and 4-phenyl-thio-semicarbazide yielded the title compound, C 18 H 23 N 3 S (common name: cis -jasmone 4-phenyl-thio-semicarbazone). Concerning the hydrogen bonding, an N-H⋯N intra-molecular inter-action is observed, forming a ring with graph-set motif S (5). In the crystal, the mol-ecules are connected into centrosymmetric dimers by pairs of N-H⋯S and C-H⋯S inter-actions, forming rings of graph-set motifs R 2 2 (8) and R 2 1 (7), with the sulfur atoms acting as double acceptors. The thio-semicarbazone entity is approximately planar, with the maximum deviation from the mean plane through the N/N/C/S/N atoms being 0.0376 (9) Å (the r.m.s.d. amounts to 0.0234 Å). The mol-ecule is substantially twisted as indicated by the dihedral angle between the thio-semicarbazone fragment and the phenyl ring, which amounts to 56.1 (5)°, and because of the jasmone fragment, which bears a chain with sp 3 -hybridized carbon atoms in the structure. The Hirshfeld surface analysis indicates that the major contributions for the crystal cohesion are: H⋯H (65.3%), H⋯C/C⋯H (16.2%), H⋯S/S⋯H (10.9%) and H⋯N/N⋯H (5.5%)., (© Oliveira et al. 2023.)

The reaction of (2 E )- N -phenyl-2-[(2 E )-3-phenyl-2-propen-1-yl-idene]hydra-zine-carbo-thio-amide (common name: cinnamaldehyde-4-phenyl-thio-semi-carbazone) deprotonated with NaOH in ethanol with an ethano-lic suspension of Pd II chloride in a 2:1 molar ratio yielded the title compound, [Pd(C 16 H 14 N 3 S) 2 ]. The anionic ligands act as metal chelators, κ 2 N 1 S -donors, forming five-membered rings with a trans -configuration. The Pd II ion is fourfold coordinated in a slightly distorted square-planar geometry. For each ligand, one H⋯S and one H⋯N intra-molecular inter-actions are observed, with S (5) and S (6) graph-set motifs. Concerning the H⋯S inter-actions, the coordination sphere resembles a hydrogen-bonded macrocyclic environment-type. In the crystal, the complexes are linked via pairs of H⋯S inter-actions, with graph-set motif R 2 2 (8), and building a mono-periodic hydrogen-bonded ribbon along [001]. The Hirshfeld surface analysis indicates that the major contributions for the crystal cohesion are: H⋯H (45.3%), H⋯C/C⋯H (28.0%), H⋯S/S⋯H (8.0%) and H⋯N/N⋯H (7.4%)., (© Melo et al. 2023.)

AChE inhibition caused by exposure to organophosphate (OP) compounds is strongly related to behavioural disorders such as depression. Malathion is an OP that already has a relationship between its exposure and behavioural changes, although few data still have its effects in a longer exposure protocol. In addition, intoxication therapy is based on the use of atropine-oxime which still has its controversial efficacy depending on the type of compound. For this, (3Z)-5-Chloro-3-(hydroxyimino)indolin-2-one (Cℓ-HIN), a compound that has properties of isatin and oxime in its structure, have shown reactivating properties in the activity of AChE that have been added to antidepressant-like effects in rats exposed to malathion in acute protocol. In this sense, effects of Cℓ-HIN on the depressive-like behaviour and AChE activity were evaluated in a protocol of subchronic exposure to malathion in rats. Male wistar rats were co-treated with Cℓ-HIN [5 mg/kg, p.o.] and/or malathion [1 or 10 mg/kg, i.p] for 20 days. The exposure to both doses of malathion increased immobility time of rats on the forced swimming test (FST). Besides, malathion inhibited the AChE activity in the prefrontal cortex of rats, but any significant difference was observed in the hippocampus. Cℓ-HIN protected against increased immobility time in the FST of those rats exposed to a dose of 1 mg/kg of malathion. Similarly, Cℓ-HIN was able to reactivate AChE activity only in that group exposed to the lowest dose of malathion. Collectively, the results of this study suggest that Cℓ-HIN is an oxime capable of reactivating AChE inhibited and presents na antidepressant-like effect in cases of prolonged exposure to malathion., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Background: Organophosphorus pesticides exert their toxic effects mainly by the inhibition of acetylcholinesterase (AChE), which is related to emotional disorders, such as depression. Atropine-oximes therapy is commonly used; however, the efficacy of oximes in the reactivation of AChE has been inconsistent. The objective of this study was to investigate the possible neuroprotective effect of (3Z)-5-Chloro-3-(hydroxyimino)indolin-2-one (Cℓ-HIN), a compound that combines the isatin and oxime functional groups, in rats exposed to malathion. The effect of Cℓ-HIN on the AChE activity and the BDNF-Trkβ pathway in the prefrontal cortex of malathion-exposed rats were tested., Methods: Wistar male rats were co-treated with Cℓ-HIN [50 mg/kg (p.o.) (3 mL/kg)] and/or malathion [250 mg/kg (i.p.) (5 mL/kg)] and performed behavioral tests twelve hours after these exposures., Results: The Cℓ-HIN reversed the increased immobility time in the forced swimming test and the decreased grooming time in the splash test induced by malathion, but any significant difference was observed in locomotion analysis. These results demonstrate the antidepressant-like effect of Cℓ-HIN. The cortical AChE activity was reactivated by Cℓ-HIN in rats exposed to malathion. Malathion induced an increase in Trkβ and a decrease in BDNF levels in the prefrontal cortex of rats, which were avoided by Cℓ-HIN., Conclusion: These findings support the hypothesis that Cℓ-HIN is an AChE reactivator with antidepressant-like properties, which is related to the improvement of BDNF-Trkβ signaling after acute exposure to malathion in rats. Thus, the results allow suggesting the potential use of Cℓ-HIN as an oxime-based therapy against the neurotoxic effects of malathion., (Copyright © 2020 Elsevier Inc. All rights reserved.)

The equimolar reaction between a racemic mixture of ( R )- and ( S )-camphorquinone with thio-semicarbazide yielded the title compound, C 11 H 17 N 3 OS [common name: ( R )- and ( S )-camphor thio-semicarbazone], which maintains the chirality of the methyl-ated chiral carbon atoms and crystallizes in the centrosymmetric space group C 2/ c . There are two mol-ecules in general positions in the asymmetric unit, one of them being the (1 R )-camphor thio-semicarbazone isomer and the second the (1 S )- isomer. In the crystal, the mol-ecular units are linked by C-H⋯S, N-H⋯O and N-H⋯S inter-actions, building a tape-like structure parallel to the (01) plane, generating R 2 1 (7) and R 2 2 (8) graph-set motifs for the H⋯S inter-actions. The Hirshfeld surface analysis indicates that the major contributions for crystal cohesion are from H⋯H (55.00%), H⋯S (22.00%), H⋯N (8.90%) and H⋯O (8.40%) inter-actions., (© Pires et al. 2020.)

The reaction in methanol of Cu II acetate monohydrate with 5-fluoro-isatin 3-oxime deprotonated with KOH in a 1:2 molar ratio and recrystallization from pyridine yielded the title compound, [Cu(C 8 H 4 FN 2 O 2 ) 2 (C 5 H 5 N) 2 ]. In the centrosymmetric complex, the anionic form of the isatin oxime acts as a κ 2 N , O donor, building five-membered metallarings. The Cu II cation is sixfold coordinated in a slightly distorted octa-hedral environment by two trans , equatorial, anionic isatin derivatives and two trans pyridine ligands in axial positions. The complexes are linked by hydrogen bonding into a three-dimensional network, which is also stabilized by π-π stacking inter-actions [centroid-to-centroid distance = 3.7352 (9) Å] and C-H⋯π contacts. The Hirshfeld surface analysis indicates that the major contributions for the crystal packing are H⋯H (31.80%), H⋯C (24.30%), H⋯O (15.20%) and H⋯F (10.80%). This work is the second report in the literature of a crystal structure of a coordination compound with isatin 3-oxime ligands (coordination chemistry).

The reaction between 5-fluoro-isatin and hydroxyl-amine hydro-chloride in acidic ethanol yields the title compound, C 8 H 5 FN 2 O 2 , whose mol-ecular structure matches the asymmetric unit and is nearly planar with an r.m.s. deviation for the mean plane through all non-H atoms of 0.0363 Å. In the crystal, the mol-ecules are linked by N-H⋯N, N-H⋯O and O-H⋯O hydrogen-bonding inter-actions into a two-dimensional network along the (100) plane, forming rings with R 2 2 (8) and R 1 2 (5) graph-set motifs. The crystal packing also features weak π-π inter-actions along the [100] direction [centroid-to-centroid distance 3.9860 (5) Å]. Additionally, the Hirshfeld surface analysis indicates that the major contributions for the crystal structure are the O⋯H (28.50%) and H⋯F (16.40%) inter-actions. An in silico evaluation of the title compound with the vascular endothelial growth factor receptor-2 (VEGFR-2) was carried out. The title compound and the selected biological target VEGFR-2 show the N-H⋯O( GLU94 ), ( CYS96 )N-H⋯O(isatine) and ( PHE95 )N-H⋯O(isatine) inter-molecular inter-actions, which suggests a solid theoretical structure-activity relationship.

The equimolar reaction between 4-(di-methyl-amino)-benzaldehyde and 2-acetyl-thio-phene in basic ethano-lic solution yields the title compound, C 15 H 15 NOS, whose mol-ecular structure matches the asymmetric unit. The mol-ecule is not planar, the dihedral angle between the aromatic and the thio-phene rings being 11.4 (2)°. In the crystal, mol-ecules are linked by C-H⋯O and weak C-H⋯S inter-actions along [100], forming R 2 2 (8) rings, and by weak C-H⋯O inter-actions along [010], forming chains with a C (6) graph-set motif. In addition, mol-ecules are connected into centrosymmetric dimers by weak C-H⋯π inter-actions, as indicated by the Hirshfeld surface analysis. The most important contributions for the crystal structure are the H⋯H (46.50%) and H⋯C (23.40%) inter-actions. The crystal packing resembles a herringbone arrangement when viewed along [100]. A mol-ecular docking calculation of the title compound with the neuraminidase enzyme was carried out. The enzyme shows ( ASN263 )N-H⋯O, ( PRO245 )C-H⋯ Cg (thio-phene ring) and ( AGR287 )C-H⋯N inter-molecular inter-actions with the title compound. The crystal structure was refined as a two-component twin with a fractional contribution to the minor domain of 0.0181 (8).

The reaction between the racemic mixture of the camphor-4-phenyl-thio-semicarbazone derivative and cadmium acetate dihydrate yielded the title compound, [Cd(C17H20N3OS)2]. The Cd(II) ion is six-coordinated in a distorted octa-hedral environment by two deprotonated thio-semicarbazone ligands acting as an O,N,S-donor in a tridentate chelating mode, forming five-membered chelate rings. In the crystal, the mol-ecules are connected via pairs of N-H⋯S and C-H⋯S inter-actions, building centrosymmetric dimers. One of the ligands is disordered in the campher unit over two sets of sites with site-occupancy factors of 0.7 and 0.3. The structure contains additional solvent mol-ecules, which are disordered and for which no reasonable split model was found. Therefore, the data were corrected for disordered solvent using the SQUEEZE routine [Spek (2015 ▸). Acta Cryst. C71, 9-18] in PLATON. Since the disordered solvents were removed by data processing, and the number of solvent entities was a suggestion only, they were not considered in the chemical formula and subsequent chemical or crystal information.

In the title compound, [Cu2(C11H13N3O3S)2(C2H6OS)2], the Cu(II) cation is N,N',O-chelated by a deprotonated hy-droxy-imino-tosyl-hydrazone ligand and coordinated by a dimethyl sulfoxide mol-ecule. One O atom from the adjacent hy-droxy-imino-tosyl-hydrazone ligand bridges the Cu(II) cation, forming the centrosymmetric dimeric complex. The cation is in an overall distorted N2O3 square-pyramidal coordination environment. The methyl-benzene ring is twisted with respect to the hydrazine fragment, with a dihedral angle of 89.54 (9)° between the planes. An intra-molecular C-H⋯O hydrogen bond occurs. In the crystal, mol-ecules are linked by weak C-H⋯O and C-H⋯S inter-actions. Weak π-π stacking is also observed between parallel benzene rings of adjacent mol-ecules, the centroid-centroid distance being 3.9592 (17) Å.

In the title compound, C14H13ClN4S, obtained from a reaction of 2-benzoyl-4-chloro-aniline with thio-semicarbazide in ethanol, the dihedral angle between the aromatic rings is 81.31 (13)°. In the crystal, the mol-ecules are linked by three N-H⋯S hydrogen bonds, forming centrosymmetric rings with set-graph motif R 2 (2)(8) and R 2 (2)(18), and resulting in the formation of a two-dimensional network lying parallel to (010).

In the title compound, C15H11BrN4OS, the least-squares plane through the 5-bromo-isatin fragment forms a dihedral angle of 13.63 (14)° with the phenyl ring. The mol-ecular conformation features intra-molecular N-H⋯N and N-H⋯O hydrogen bonds. In the crystal, mol-ecules are connected via pairs of N-H⋯O inter-actions into centrosymmetric dimers. Additionally, π-π stacking inter-actions link mol-ecules into chains parallel to the a axis with short C⋯C distances being observed between the phenyl and thio-carbonyl [3.236 (8) Å] groups and between the thio-carbonyl and carbonyl [3.351 (4) Å] groups of stacked mol-ecules.

The title mol-ecule, C9H7BrN4OS, is essentially planar [r.m.s. deviation = 0.066 (2) Å], the maximum deviation from the mean plane through the non-H atoms being 0.190 (3) Å for the terminal amine N atom. In the crystal, mol-ecules are linked through N-H⋯O and N-H⋯S inter-actions, generating infinite chains along the b-axis direction. In turn, the chains are stacked along the a axis via π-π inter-actions [centroid-centroid distance = 3.470 (2) Å] and further connected by N-H⋯Br inter-actions into a three-dimensional network. An intra-molecular N-H⋯O hydrogen bond is also observed.

In the title compound, C10H11N3O2S, the 1,3-benzodioxole and hydrazinecarbothio-amide fragments are nearly planar [(mean deviations from planarity for non-H atoms of 0.0325 (12) Å and 0.0707 (10) Å, respectively] and subtend a dihedral angle of 29.06 (5)°. In the crystal, mol-ecules are linked by pairs of almost linear N-H⋯S hydrogen bonds, forming inversion dimers. These dimers are additionally connected by weaker and strongly bent N-H⋯S inter-actions into chains along [101]. There is one additional weak N-H⋯O contact which, if considered as an inter-action, leads to the formation of a three-dimensional network.

Methamidophos is one of the most toxic organophosphorus (OP) compounds. It acts via phosphorylation of a serine residue in the active site of acetylcholinesterase (AChE) and butyrylcholinesterase (BChE), leading to enzyme inactivation. Different oximes have been developed to reverse this inhibition. Thus, our work aimed to test the protective or reactivation capability of pralidoxime and obidoxime, as well as two new oximes synthesised in our laboratory, on human and rat cholinesterases inhibited by methamidophos. In addition, we performed molecular docking studies in non-aged methamidophos-inhibited AChE to understand the mechanisms involved. Our results suggested that pralidoxime protected and reactivated methamidophos-inhibited rat brain AChE. Regarding human erythrocyte AChE, all oximes tested protected and reactivated the enzyme, with the best reactivation index observed at the concentration of 50 μM. Concerning BChE, butane-2,3-dionethiosemicarbazone oxime (oxime 1) was able to protect and reactivate the methamidophos-inhibited BChE by 45% at 50 μM, whereas 2(3-(phenylhydrazono)butan-2-one oxime (oxime 2) reactivated 28% of BChE activity at 100 μM. The two classical oximes failed to reactivate BChE. The molecular docking study demonstrated that pralidoxime appears to be better positioned in the active site to attack the O-P moiety of the inhibited enzyme, being near the oxyanion hole, whereas our new oximes were stably positioned in the active site in a manner similar to that of obidoxime. In conclusion, our work demonstrated that the newly synthesised oximes were able to reactivate not only human erythrocyte AChE but also human plasma BChE, which could represent an advantage in the treatment of OP compounds poisoning., (© 2012 The Authors Basic & Clinical Pharmacology & Toxicology © 2012 Nordic Pharmacological Society.)

Organophosphates (OPs), which are widely used as pesticides, are acetylcholinesterase (AChE) and butyrylcholinesterase (BChE) inhibitors. The inactivation of AChE results in the accumulation of acetylcholine at cholinergic receptor sites, causing a cholinergic crisis that can lead to death. The classical treatment for OP poisoning is administration of oximes, but these compounds are ineffective in some cases. Here we determined whether the new compound isatin-3-N(4)-benzilthiosemicarbazone (IBTC), which in our previous study proved to be an antioxidant and antiatherogenic molecule, could protect and reactivate AChE and BChE. Toxicity of IBTC after subcutaneous injection in mice was measured using assays for oxidized diclorofluoresceine (DCF), thiobarbituric acid reactive substances (TBARS), non-protein thiol (NPSH) levels, and catalase (CAT), sodium potassium (Na(+)/K(+)) ATPase, delta-aminolevulinic acid dehydratase (ALA-D), and glutathione peroxidases (GPx) enzyme activities. The cytotoxicity was evaluated and the enzymatic activity of cholinesterase was measured in human blood samples. Molecular docking was used to predict the mechanism of IBTC interactions with the AChE active site. We found that IBTC did not increase the amount of DCF-RS or TBARS, did not reduce NPSH levels, and did not increase CAT, (Na(+)/K(+)) ATPase, ALA-D, or GPx activities. IBTC protected and reactivated both AChE and BChE activities. Molecular docking predicted that IBTC is positioned at the peripheral anionic site and in the acyl binding pocket of AChE and can interact with methamidophos, releasing the enzyme's active site. Our results suggest that IBTC, besides being an antioxidant and a promising antiatherogenic agent, is a non-toxic molecule for methamidophos poisoning treatment., (Copyright © 2012 Elsevier Ltd. All rights reserved.)

The reaction of 5-bromo-salicyl-aldehyde thio-semicarbazone with nickel acetate tetra-hydrate and pyridine yielded the title compound, [Ni(C(8)H(6)BrN(3)OS)(C(5)H(5)N)]. The Ni(II) atom is four-coordinated in a square-planar environment by one deprotonated dianionic thio-semicarbazone ligand, acting in a tridentate chelating mode through N, O and S atoms forming two metalla-rings, and by one pyridine mol-ecule. The complex mol-ecules are linked into dimers by pairs of centrosym-metrical N-H⋯N inter-actions. In addition, mol-ecules are connected through inter-molecular Br⋯Br inter-actions [3.545 (1) Å], forming chains along the b-axis direction.

The reaction of cadmium acetate dihydrate with 2-acetyl-pyridine (4-phenyl-thio-semicarbazone) yielded the title compound, [Cd(C(14)H(13)N(4)S)(2)]. The Cd(II) atom is six-coordin-ated in a distorted octa-hedral environment by two deproton-ated thio-semicarbazone ligands acting in a tridentate chelating mode through two N and one S atoms, forming metalla-rings. In the crystal, mol-ecules are connected through inversion centers via pairs of N-H⋯S inter-actions, building a one-dimensional hydrogen-bonded polymer along [0-1-1].

The title mol-ecule, C(5)H(5)N(5)O(3)S, is approximately planar, with a maximum deviation from the mean plane through the non-H atoms of 0.182 (3) Å for the amine N atom. In the crystal, mol-ecules are connected via N-H⋯O and N-H⋯S inter-actions, building a three-dimensional hydrogen-bonded network. Additionally, a weak intra-molecular N-H⋯O hydrogen bond is observed.

In the title compound, C(11)H(15)N(3)O(3)S, the C-S-N(H)-N linkage is nonplanar, the torsion angle being 75.70 (12)°. The compound has two almost planar fragments linked to the S atom: the hydrazone-derivative fragment [(HONC(4)H(6))N-N(H)-] and the tolyl fragment (C(7)H(7)-) have maximum deviations from the mean plane through the non-H atoms of 0.0260 (10) and 0.0148 (14) Å, respectively. The two planar fragments make an inter-planar angle of 79.47 (5)°. In the crystal, mol-ecules are connected through inversion centers via pairs of N-H⋯O and O-H⋯N hydrogen bonds.

Our group of studies investigated the action of butane-2,3-dione thiosemicarbazone oxime against the testicular damage caused by cadmium chloride (CdCl(2)) in mice. Mice received a single injection of CdCl(2 )(5 mg/kg, intraperitoneally) and, after thirty minutes, the oxime (10 mg/kg, subcutaneously) was administered. Twenty four hours after the last administration, the animals were killed by cervical dislocation and the testes and serum were removed for analysis. The parameters determined were δ-aminolevulinate dehydratase (δ-ALA-D), myeloperoxidase (MPO), glutathione-S-transferase (GST) and glutathione peroxidase (GPx) activities. The levels of thiobarbituric acid-reactive substances (TBARS), nonprotein thiols (NPSH), ascorbic acid, cadmium and testosterone were also determined. In addition, histological analysis and cytokines quantification (IL-1, IL-6, IL-10, TNF-α and IFN-γ) were performed. Our results demonstrated that the oxime was effective in restoring the inhibition in δ-ALA-D activity induced by CdCl(2). The activation of MPO and increase in IL-1, IL-6, TNF-α and IFN-γ levels induced by CdCl(2) were also reduced by oxime. IL-10, which was reduced by cadmium, was restored by oxime administration. In addition, the oxime was effective in restoring the increase in TBARS levels and the reduction on NPSH levels induced by CdCl(2). Our results demonstrated that oxime was effective in containing the histological alterations induced by CdCl(2). In addition, oxime was able to increase the testosterone levels, reduced by cadmium exposure. In conclusion, the oxime tested was effective in reducing the testicular damage induced by CdCl(2) in mice. The beneficial effects of this oxime are related to its antioxidant and anti-inflammatory action.

In the title molecule, C(9)H(7)N(5)O(3)S, there is an intramolecular N-H⋯O. The molecule is essentially planar, with the maximum deviation from the mean plane of the 18 non-H atoms being 0.135 (2) Å for the amine N atom. In the crystal, the molecules are connected via intermolecular N-H⋯O and N-H⋯S hydrogen bonds, forming two-dimensional networks lying parallel to (10[Formula: see text]). They are separated by an interplanar distance of 3.3214 (9) Å, leading to π-π interactions which stabilize the crystal structure.

Aims: Several lines of evidence support the hypotheses that the oxidation of low density lipoprotein (LDL) may play a crucial role in the initiation and progression of atherosclerosis. Oxidative stress is one of the causes of the overproduction of reactive species that increase the formation of oxidized LDL. Thiosemicarbazones are compounds used in anticancer, antiviral and antifungal therapy; however, its redox activity has been controversial. Thus, we tested, in vitro, a possible antioxidant activity of a thiosemicarbazone derivate, the isatin-3-N(4)-benzilthiosemicarbazone (IBTC)., Main Methods: We measured the conjugated diene formation in serum and LDL as well as the loss of tryptophan fluorescence in LDL induced by two oxidant agents, 2,2-azobis(2-amidinopropane dihydrochloride) (AAPH) and Cu(2+). Thiobarbituric acid reactive substances (TBARS) formation in LDL and in different rat tissues was also assessed. The toxicity of IBTC was measured using aortic slices viability assay., Key Findings: Our results show that IBTC significantly reduced the AAPH and Cu(2+)-induced formation of conjugated dienes, increased in a dose-dependent manner the lag phase and the t(1/2) of tryptophan fluorescence, and reduced the TBARS formation in LDL, plasma and rat tissues, showing no toxicity to aortic slices., Significance: These results indicate that IBTC is a good antioxidant and a promising antiatherogenic agent for further studies in vivo., (Copyright © 2011 Elsevier Inc. All rights reserved.)

In the crystal structure of the title compound, C(9)H(7)BrN(4)OS·C(2)H(3)N, the mol-ecules are connected via N-H⋯O and N-H⋯S inter-actions into zigzag chains perpendicular to [001]. The mol-ecules in these chains are additionally linked to acetonitrile solvent mol-ecules through N-H⋯N hydrogen bonding. The mol-ecules are arranged in layers and are stacked in the direction of the c axis indicative of π-π inter-actions, with distance = 3.381 (7) Å for the C⋯C interaction parallel to [001]. An intra-molecular N-H⋯O hydrogen bond is also observed in the main mol-ecule.

Unlabelled: Quantitative imaging biomarkers could speed the development of new treatments for unmet medical needs and improve routine clinical care. However, it is not clear how the various regulatory and nonregulatory (eg, reimbursement) processes (often referred to as pathways) relate, nor is it clear which data need to be collected to support these different pathways most efficiently, given the time- and cost-intensive nature of doing so. The purpose of this article is to describe current thinking regarding these pathways emerging from diverse stakeholders interested and active in the definition, validation, and qualification of quantitative imaging biomarkers and to propose processes to facilitate the development and use of quantitative imaging biomarkers. A flexible framework is described that may be adapted for each imaging application, providing mechanisms that can be used to develop, assess, and evaluate relevant biomarkers. From this framework, processes can be mapped that would be applicable to both imaging product development and to quantitative imaging biomarker development aimed at increasing the effectiveness and availability of quantitative imaging., Supplemental Material: http://radiology.rsna.org/lookup/suppl/doi:10.1148/radiol.10100800/-/DC1., (RSNA, 2011)

The reaction of hydroxyl-amine hydro-chloride with isatin in ethanol, catalysed with HCl and neutralized with Na(2)CO(3), yielded the one-dimensional coordination polymer, catena-poly[[[aqua-sodium]-di-μ-aqua-[aqua-sodium]-bis-(μ-2-oxoindoline-2,3-dione 3-oximato)] tetra-kis-(oxoindoline-2,3-dione 3-oxime)], {[Na(C(8)H(5)N(2)O(2))(H(2)O)(2)]·2C(8)H(6)N(2)O(2)}(n). The Na(I) atom has a six-coordinate distorted-octa-hedral environment. Isatine-3-oximate O atoms and water mol-ecules bridge adjacent Na atoms, forming a one-dimensional polymeric structure parallel to [100]. Each isatine-3-oxime dimerizes through N-H⋯O interactions and in addition each oxime is linked to a coordination polymer. Thus, coordination polymers are linked by O-H⋯O and O-H⋯N interactions from isatine-3-oxime dimers, building a two-dimensional network parallel to [110].

Oximes are compounds generally used to reverse the acetylcholinesterase (AChE) inhibition caused by organophosphates (OPs). The aim of this study was to examine the capacity of the butane-2,3-dionethiosemicarbazone oxime to scavenge different forms of reactive species (RS) in vitro, as well as counteract their formation. The potential antioxidant and toxic activity of the oxime was assayed both in vitro and ex vivo. The obtained results indicate a significant hydrogen peroxide (H2O2), nitric oxide (NO) and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity at 0.275, 0.5 and 5microM of oxime, respectively (p< or =0.05). The oxime exhibited a powerful inhibitory effect on dihydroxybenzoate formation (25microM) (p< or =0.05) and also decreased deoxyribose degradation induced by Fe2+ and via Fenton reaction (0.44 and 0.66mM, respectively) (p< or =0.05). The oxime showed a significant inhibitory effect on sigma-phenantroline reaction with Fe2+ (0.4mM) suggesting a possible interaction between the oxime and iron. A significant decrease in the basal and pro-oxidant-induced lipid peroxidation in brain, liver, and kidney of mice was observed both in vitro and ex vivo (p< or =0.05). In addition, in our ex vivo experiments the oxime did not depict any significant changes in thiol levels of liver, kidney and brain as well as did not modify the delta-aminolevulinate dehydratase (delta-ALA-D) activity in these tissues. Taken together our results indicate an in vitro and ex vivo antioxidant activity of the oxime possibly due to its scavenging activity toward different RS and a significant iron interaction.

Aims: Several lines of evidence support the hypothesis that the oxidation of low density lipoprotein (LDL) may play a crucial role in the initiation and progression of atherosclerosis. Various studies have shown a positive effect of antioxidant compounds on oxidative modification of LDL and atherogenesis. In view of this, we have investigated the possible antioxidant activity of two new oximes against Cu2+- induced LDL and serum oxidation. Oximes are used in organophosphate (OP) poisoning acting by restoring the cholinesterase function. However, their antioxidant capacities are not well understood and poorly studied., Main Methods: We measured, in a Cu2+-induced oxidation, the conjugated dienes formation in serum and LDL and the loss of tryptophan fluorescence as well as the TBARS formation in the LDL., Key Findings: Our results showed that both oximes act as antioxidant and they are able to prevent LDL oxidation in a concentration-dependent manner. When human LDL or serum was oxidized by Cu2+, our oximes showed a significant increase in the lag phase of conjugated dienes and a significant decrease in the thiobarbituric acid reactive substances production. Moreover, oximes protected tryptophan residues of ApoB-100 in the early stage of LDL oxidation and during the subsequent propagation phase., Significance: These results indicated for the first time that oximes have a potential antioxidant activity and they could act in the prevention of LDL and serum oxidation. Thus, we speculated that our oximes could act as antiatherogenic compounds besides their well described role as antidote for organophosphate poisoning.

Over the past 2 years, ongoing efforts have been made to reevaluate and restructure the way physics education is provided to radiology residents. Program directors and faculty from North American radiology residency programs were surveyed about how physics is being taught and what resources are currently being used for their residents. Substantial needs were identified for additional educational resources in physics, better integration of physics into clinical training, and a standardized physics curriculum closely linked to the initial certification examination of the American Board of Radiology., ((c) RSNA, 2008.)

Oximes are a class of compounds normally used to reverse the acetylcholinesterase (AChE) inhibition caused by organophosphates (OPs). Conversely, researches focusing on the possible antioxidant properties of these compounds are lacking in the literature. The aim of this study was to investigate the potential antioxidant and toxic properties of 3-(phenylhydrazono) butan-2-one oxime in mice. In vitro, hydrogen peroxide-induced lipid peroxidation was decreased by low concentrations of the oxime (0.1-1.0 microM); (P < 0.05). Similarly, lipoperoxidation induced by malonate and iron (Fe2+) was significantly decreased by the oxime (0.4-1.0 microM) (P < 0.05). Oxime pre-treatment did not modify the basal peroxidation level nor prevented the induced lipid peroxidation determined ex-vivo. The present results suggest that 3-(phenylhydrazono) butan-2-one oxime could be a good antioxidant compound. The absence of toxicity signs after in vivo administration of 3-(phenylhydrazono) butan-2-one oxime to mice may indicate that it could be a safe drug for further studies.