7038-40-6Relevant academic research and scientific papers
Structures, Spectroscopic Properties, and Dioxygen Reactivity of 5- and 6-Coordinate Nonheme Iron(II) Complexes: A Combined Enzyme/Model Study of Thiol Dioxygenases
Gordon, Jesse B.,McGale, Jeremy P.,Prendergast, Joshua R.,Shirani-Sarmazeh, Zahra,Siegler, Maxime A.,Jameson, Guy N. L.,Goldberg, David P.
, p. 14807 - 14822 (2018/11/03)
The synthesis of four new FeII(N4S(thiolate)) complexes as models of the thiol dioxygenases are described. They are composed of derivatives of the neutral, tridentate ligand triazacyclononane (R3TACN; R = Me, iPr) and 2-aminobenzenethiolate (abtx X = H, CF3), a non-native substrate for thiol dioxygenases. The coordination number of these complexes depends on the identity of the TACN derivative, giving 6-coordinate (6-coord) complexes for FeII(Me3TACN)(abtx)(OTf) (1: X = H; 2: X = CF3) and 5-coordinate (5-coord) complexes for [FeII(iPr3TACN)(abtx)](OTf) (3: X = H; 4: X = CF3). Complexes 1-4 were examined by UV-vis, 1H/19F NMR, and M?ssbauer spectroscopies, and density functional theory (DFT) calculations were employed to support the data. M?ssbauer spectroscopy reveals that the 6-coord 1-2 and 5-coord 3- 4 exhibit distinct spectra, and these data are compared with that for cysteine-bound CDO, helping to clarify the coordination environment of the cys-bound FeII active site. Reaction of 1 or 2 with O2 at -95 °C leads to S-oxygenation of the abt ligand, and in the case of 2, a rare di(sulfinato)-bridged complex, [Fe2III(μ-O)((2-NH2)p-CF3C6H3SO2)2](OTf)2 (5), was obtained. Parallel enzymatic studies on the CDO variant C93G were carried out with the abt substrate and show that reaction with O2 leads to disulfide formation, as opposed to S-oxygenation. The combined model and enzyme studies show that the thiol dioxygenases can operate via a 6-coord FeII center, in contrast to the accepted mechanism for nonheme iron dioxygenases, and that proper substrate chelation to Fe appears to be critical for S-oxygenation.
Simultaneous nitrosylation and N-nitrosation of a Ni-thiolate model complex of Ni-containing SOD
Truong, Phan T.,Broering, Ellen P.,Dzul, Stephen P.,Chakraborty, Indranil,Stemmler, Timothy L.,Harrop, Todd C.
, p. 8567 - 8574 (2018/11/30)
Nitric oxide (NO) is used as a substrate analogue/spectroscopic probe of metal sites that bind and activate oxygen and its derivatives. To assess the interaction of superoxide with the Ni center in Ni-containing superoxide dismutase (NiSOD), we studied the reaction of NO+ and NO with the model complex, Et4N[Ni(nmp)(SPh-o-NH2-p-CF3)] (1; nmp2- = dianion of N-(2-mercaptoethyl)picolinamide; -SPh-o-NH2-p-CF3 = 2-amino-4-(trifluoromethyl)benzenethiolate) and its oxidized analogue 1ox, respectively. The ultimate products of these reactions are the disulfide of -SPh-o-NH2-p-CF3 and the S,S-bridged tetrameric complex [Ni4(nmp)4], a result of S-based redox activity. However, introduction of NO to 1 affords the green dimeric {NiNO}10 complex (Et4N)2[{Ni(κ2-SPh-o-NNO-p-CF3)(NO)}2] (2) via NO-induced loss of nmp2- as the disulfide and N-nitrosation of the aromatic thiolate. Complex 2 was characterized by X-ray crystallography and several spectroscopies. These measurements are in-line with other tetrahedral complexes in the {NiNO}10 classification. In contrast to the established stability of this metal-nitrosyl class, the Ni-NO bond of 2 is labile and release of NO from this unit was quantified by trapping the NO with a CoII-porphyrin (70-80% yield). In the process, the Ni ends up coordinated by two o-nitrosaminobenzenethiolato ligands to result in the structurally characterized trans-(Et4N)2[Ni(SPh-o-NNO-p-CF3)2] (3), likely by a disproportionation mechanism. The isolation and characterization of 2 and 3 suggest that: (i) the strongly donating thiolates dominate the electronic structure of Ni-nitrosyls that result in less covalent Ni-NO bonds, and (ii) superoxide undergoes disproportionation via an outer-sphere mechanism in NiSOD as complexes in the {NiNO}9/8 state have yet to be isolated.
CONDENSED HETEROCYCLIC COMPOUND HAVING CYCLOALKYLPYRIDYL GROUP OR SALT THEREOF, AGRICULTURAL AND HORTICULTURAL INSECTICIDE COMPRISING THE COMPOUND, AND METHOD FOR USING THE INSECTICIDE
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, (2018/09/24)
An object of the present invention is to provide and develop novel agricultural and horticultural insecticides in view of the still immense damage caused by insect pests etc. and the emergence of insect pests resistant to existing insecticides in crop production in the fields of agriculture, horticulture and the like. Provided are a condensed heterocyclic compound represented by the general formula (1): {wherein R1 represents an ethyl group, R2 represents a cycloalkyl group, R3 represents a haloalkyl group, A, A2 and A3 each represent a nitrogen atom or a CH group, A1 represents N-Me, m represents 0 or 2, and n represents 1} or a salt thereof; an agricultural and horticultural insecticide comprising the compound or a salt thereof as an active ingredient; and a method for using the insecticide.
Accessing Ni(III)-thiolate versus Ni(II)-thiyl bonding in a family of Ni-N2S2 synthetic models of NiSOD
Broering, Ellen P.,Dillon, Stephanie,Gale, Eric M.,Steiner, Ramsey A.,Telser, Joshua,Brunold, Thomas C.,Harrop, Todd C.
, p. 3815 - 3828 (2015/05/04)
Superoxide dismutase (SOD) catalyzes the disproportionation of superoxide (O2?-) into H2O2 and O2(g) by toggling through different oxidation states of a first-row transition metal ion at its active site. Ni-containing SODs (NiSODs) are a distinct class of this family of metalloenzymes due to the unusual coordination sphere that is comprised of mixed N/S-ligands from peptide-N and cysteine-S donor atoms. A central goal of our research is to understand the factors that govern reactive oxygen species (ROS) stability of the Ni-S(Cys) bond in NiSOD utilizing a synthetic model approach. In light of the reactivity of metal-coordinated thiolates to ROS, several hypotheses have been proffered and include the coordination of His1-Nδ to the Ni(II) and Ni(III) forms of NiSOD, as well as hydrogen bonding or full protonation of a coordinated S(Cys). In this work, we present NiSOD analogues of the general formula [Ni(N2S)(SR′)]-, providing a variable location (SR′ = aryl thiolate) in the N2S2 basal plane coordination sphere where we have introduced o-amino and/or electron-withdrawing groups to intercept an oxidized Ni species. The synthesis, structure, and properties of the NiSOD model complexes (Et4N)[Ni(nmp)(SPh-o-NH2)] (2), (Et4N)[Ni(nmp)(SPh-o-NH2-p-CF3)] (3), (Et4N)[Ni(nmp)(SPh-p-NH2)] (4), and (Et4N)[Ni(nmp)(SPh-p-CF3)] (5) (nmp2- = dianion of N-(2-mercaptoethyl)picolinamide) are reported. NiSOD model complexes with amino groups positioned ortho to the aryl-S in SR′ (2 and 3) afford oxidized species (2ox and 3ox) that are best described as a resonance hybrid between Ni(III)-SR and Ni(II)-?SR based on ultraviolet-visible (UV-vis), magnetic circular dichroism (MCD), and electron paramagnetic resonance (EPR) spectroscopies, as well as density functional theory (DFT) calculations. The results presented here, demonstrating the high percentage of S(3p) character in the highest occupied molecular orbital (HOMO) of the four-coordinate reduced form of NiSOD (NiSODred), suggest that the transition from NiSODred to the five-coordinate oxidized form of NiSOD (NiSODox) may go through a four-coordinate Ni-?S(Cys) (NiSODox-Hisoff) that is stabilized by coordination to Ni(II).
Synthesis and properties of arsenic(III)-reactive coumarin-appended benzothiazolines: A new approach for inorganic arsenic detection
Ezeh, Vivian C.,Harrop, Todd C.
, p. 2323 - 2334 (2013/04/10)
The EPA has established a maximum contaminant level (MCL) of 10 ppb for arsenic (As) in drinking water requiring sensitive and selective detection methodologies. To tackle this challenge, we have been active in constructing small molecules that react specifically with As3+ to furnish a new fluorescent species (termed a chemodosimeter). We report in this contribution, the synthesis and spectroscopy of two small-molecule fluorescent probes that we term ArsenoFluors (or AFs) as As-specific chemodosimeters. The AFs (AF1 and AF2) incorporate a coumarin fluorescent reporter coupled with an As-reactive benzothiazoline functional group. AFs react with As3+ to yield the highly fluorescent coumarin-6 dye (C6) resulting in a 20-25-fold fluorescence enhancement at λem ～ 500 nm with detection limits of 0.14-0.23 ppb in tetrahydrofuran (THF) at 298 K. The AFs also react with common environmental As3+ sources such as sodium arsenite in a THF/CHES (N-cyclohexyl-2-aminoethanesulfonic acid) (1:1, pH 9, 298 K) mixture resulting in a modest fluorescence turn-ON (1.5- to 3-fold) due to the quenched nature of coumarin-6 derivatives in high polarity solvents. Bulk analysis of the reaction of the AFs with As3+ revealed that the C6 derivatives and the Schiff-base disulfide of the AFs (SB1 and SB2) are the ultimate end-products of this chemistry with the formation of C6 being the principle photoproduct responsible for the As3+-specific turn-ON. It appears that a likely species that is traversed in the reaction path is an As-hydride-ligand complex that is a putative intermediate in the proposed reaction path.
Synthesis and biological properties of benzothiazole, benzoxazole, and chromen-4-one analogues of the potent antitumor agent 2-(3,4-dimethoxyphenyl)-5- fluorobenzothiazole (PMX 610, NSC 721648)
Aiello, Stefania,Wells, Geoffrey,Stone, Erica L.,Kadri, Hachemi,Bazzi, Rana,Bell, David R.,Stevens, Malcolm F. G.,Matthews, Charles S.,Bradshaw, Tracey D.,Westwell, Andrew D.
experimental part, p. 5135 - 5139 (2009/08/09)
New fluorinated 2-aryl-benzothiazoles, -benzoxazoles, and -chromen-4-ones have been synthesized and their activity against MCF-7 and MDA 468 breast cancer cell lines compared with the potent antitumor benzothiazole 5. Analogues such as 9a,b and 12a,d yielded submicromolar GI50 values in both cell lines; however, none of the new compounds approached 5 in terms of antitumor potency. For 5, binding to the aryl hydrocarbon receptor appeared to be necessary but not sufficient for growth inhibition.
Identification of a novel series of tetrahydrodibenzazocines as inhibitors of 17β-hydroxysteroid dehydrogenase type 3
Fink, Brian E.,Gavai, Ashvinikumar V.,Tokarski, John S.,Goyal, Bindu,Misra, Raj,Xiao, Hai-Yun,Kimball, S. David,Han, Wen-Ching,Norris, Derek,Spires, Thomas E.,You, Dan,Gottardis, Marco M.,Lorenzi, Matthew V.,Vite, Gregory D.
, p. 1532 - 1536 (2007/10/03)
A novel series of 17β-hydroxysteroid dehydrogenase type 3 (17β-HSD3) inhibitors has been identified. These inhibitors, based on a dibenzazocine core, exhibited picomolar to low nanomolar inhibition of 17β-HSD3 in cell-free enzymatic as well as in cell-based transcriptional reporter assays.
