New Drosophila promoter-associated architectural protein Mzfp1 interacts with CP190 and is required for housekeeping gene expression and insulator activity.

In Drosophila, a group of zinc finger architectural proteins recruits the CP190 protein to the chromatin, an interaction that is essential for the functional activity of promoters and insulators. In this study, we describe a new architectural C2H2 protein called Madf and Zinc-Finger Protein 1 (Mzfp1) that interacts with CP190. Mzfp1 has an unusual structure that includes six C2H2 domains organized in a C-terminal cluster and two tandem MADF domains. Mzfp1 predominantly binds to housekeeping gene promoters located in both euchromatin and heterochromatin genome regions. In vivo mutagenesis studies showed that Mzfp1 is an essential protein, and both MADF domains and the CP190 interaction region are required for its functional activity. The C2H2 cluster is sufficient for the specific binding of Mzfp1 to regulatory elements, while the second MADF domain is required for Mzfp1 recruitment to heterochromatin. Mzfp1 binds to the proximal part of the Fub boundary that separates regulatory domains of the Ubx and abd-A genes in the Bithorax complex. Mzfp1 participates in Fub functions in cooperation with the architectural proteins Pita and Su(Hw). Thus, Mzfp1 is a new architectural C2H2 protein involved in the organization of active promoters and insulators in Drosophila.

Mechanisms of Interaction between Enhancers and Promoters in Three Drosophila Model Systems.

In higher eukaryotes, the regulation of developmental gene expression is determined by enhancers, which are often located at a large distance from the promoters they regulate. Therefore, the architecture of chromosomes and the mechanisms that determine the functional interaction between enhancers and promoters are of decisive importance in the development of organisms. Mammals and the model animal Drosophila have homologous key architectural proteins and similar mechanisms in the organization of chromosome architecture. This review describes the current progress in understanding the mechanisms of the formation and regulation of long-range interactions between enhancers and promoters at three well-studied key regulatory loci in Drosophila.

Transcriptional Readthrough Interrupts Boundary Function in Drosophila.

In higher eukaryotes, distance enhancer-promoter interactions are organized by topologically associated domains, tethering elements, and chromatin insulators/boundaries. While insulators/boundaries play a central role in chromosome organization, the mechanisms regulating their functions are largely unknown. In the studies reported here, we have taken advantage of the well-characterized Drosophila bithorax complex (BX-C) to study one potential mechanism for controlling boundary function. The regulatory domains of BX-C are flanked by boundaries, which block crosstalk with their neighboring domains and also support long-distance interactions between the regulatory domains and their target gene. As many lncRNAs have been found in BX-C, we asked whether readthrough transcription (RT) can impact boundary function. For this purpose, we took advantage of two BX-C boundary replacement platforms, Fab-7attP50 and F2attP, in which the Fab-7 and Fub boundaries, respectively, are deleted and replaced with an attP site. We introduced boundary elements, promoters, and polyadenylation signals arranged in different combinations and then assayed for boundary function. Our results show that RT can interfere with boundary activity. Since lncRNAs represent a significant fraction of Pol II transcripts in multicellular eukaryotes, it is therefore possible that RT may be a widely used mechanism to alter boundary function and regulation of gene expression.

Reactivity of Transition Metal Gallylene Complexes Toward Substrates with Multiple Carbon-Element Bonds.

Reactivity of transition metal complexes containing the redox-active gallylene (dpp-bian)Ga ligand (dpp-bian = 1,2-bis[(2,6-diisopropylphenyl)imino]acenaphthene) toward isocyanide, isocyanate, isothiocyanate, and ketene substrates is described. The reaction of [(dpp-bian)GaCr(CO)5] (1) with tBuNC results in a dative complex [(dpp-bian)Ga(CNtBu)Cr(CO)5] (2), while compound [(dpp-bian)GaCr(CO)5]2[Na(THF)2]2 (3) reacts with tBuNC to give the coordination polymer [(dpp-bian)GaCr(CO)5][Na(CNtBu)(THF)]n (5). Treatment of [(dpp-bian)GaCr(CO)5]2[Na(THF)2]2 with an excess of PhNCO results in trimerization of the latter and formation of complex [(dpp-bian)GaCr(CO)5][Na(PhNCO)3(Et2O) (DME)] (4). [(dpp-bian)GaFeCp(CO)2] (7) treated with Ph2CCO or PhNCS results in cycloaddition products [(dpp-bian)(Ph2CCO)GaFeCp(CO)2] (8) and [(dpp-bian)(PhNCS)GaFeCp(CO)2] (9). The formation of 2 and 9 was found to be reversible, which offers a means for facile regulation of transition metal center reactivity and cooperative substrate activation. New compounds were characterized by EPR (2), NMR (4, 8, and 9), and IR spectroscopy (2, 4, 5, 8, and 9). The molecular structures of 2, 4, 5, 8, and 9 were established by single-crystal X-ray diffraction analysis. Electronic structures of the compounds have been examined by DFT calculations.

Reversible Addition of Carbon Dioxide to Main Group Metal Complexes at Temperatures about 0 °C.

The reaction of dialane [LAl-AlL] (1; L=dianion of 1,2-bis[(2,6-diisopropylphenyl)imino]acenaphthene, dpp-bian) with carbon dioxide results in two different products depending on solvent. In toluene at temperatures of about 0 °C, the reaction gives cycloadduct [L(CO2 )Al-Al(O2 C)L] (2), whereas in diethyl ether, the reaction affords oxo-bridged carbamato derivative [L(CO2 )(Et2 O)Al(µ-O)AlL] (3). The DFT and QTAIM calculations provide reasonable explanations for the reversible formation of complex 2 in the course of two subsequent (2+4) cycloaddition reactions. Consecutive transition states with low activation barriers were revealed. Also, the DFT study demonstrated a crucial effect of diethyl ether coordination to aluminium on the reaction of dialane 1 with CO2 . The optimized structures of key intermediates were obtained for the reactions in the presence of Et2 O; calculated thermodynamic parameters unambiguously testify the irreversible formation of the product 3.

Reactions of Iso(thio)cyanates with Dialanes: Cycloaddition, Reductive Coupling, or Cleavage of the C═S or C═O Bond.

The dialanes [(dpp-Bian)Al-Al(dpp-Bian)] (1) and [(dpp-dad)Al(THF)-(THF)Al(dpp-dad)] (2) (dpp-Bian = 1,2-[(2,6-iPr2C6H3)NC]2C12H6, dpp-dad = [(2,6-iPr2C6H3)NC(CH3)]2) react with some isothiocyanates, isocyanates, and diphenylketene via [2 + 4] cycloaddition of the C═O or C═S bond across the C═C-N-Al fragment to afford complexes [L(X═C-Y)Al-Al(X═C-Y)L] with an intact Al-Al single bond (3, L = dpp-Bian, X = PhN, Y = O; 4, L = dpp-Bian, X = Ph2C, Y = O; 6, L = dpp-dad, X = BnN, Y = S; 7, L = dpp-dad, X = tBuN, Y = O; 8, L = dpp-dad, X = iPrN, Y = S; and 9, L = dpp-dad, X = CyN, Y = S). A mixed C═N and C═O mode cycloadduct, [(dpp-Bian)(TosN═C-O)Al-Al(TosN-C═O)(dpp-Bian)] 5, was obtained in the reaction of 1 with tosylisocyanate. Heating the solution of 3 resulted in a thermal transformation and a change of the cycloaddition mode from C═O to C═N to give the product [(dpp-Bian)(PhN-C═O)Al(O)Al(PhN-C═O)(dpp-Bian)] 10. The reduction of 7 and 8 with Na yielded the products [Na(THF)n]2[(dpp-dad-H)(X═C-Y)Al]2 (12, X = iPrN, Y = S, n = 2 and 13, X = tBuN, Y = O, n = 3) in which one of the methyl groups of the backbone of the initial dpp-dad ligand was dehydrogenated. When 2 was reacted with the bulky adamantyl isocyanate AdNCO, the C-C coupling of two substrates occurred to form 14 [(dpp-dad)Al(O═C-NAd)2Al(dpp-dad)] in which the coupled dianionic oxamide ligand bridged two Al atoms in a µ,η4-N,O/N,O mode. Moreover, in the presence of 2.0 equiv of Na metal, precursor 2 reacts with tBuNCS, p-TolylNCS, or Me3SiNCO, possibly through the reduced AlI intermediate, to yield the sulfur- or oxygen-bridged dimer [Na(solv)n]2[(dpp-dad)Al(µ-E)]2 (15, E = S, solv = THF, n = 3 and 16, E = O, solv = DME, n = 2) upon C═S or C═O bond cleavage. Dialane 1 reacts with dimethylsulfone to give a Lewis adduct [(dpp-Bian)(Me2SO2)Al]2 (17), which releases dimethylsulfone upon heating. The diamagnetic compounds 3-10 and 12-17 were characterized by NMR and IR spectroscopy. The molecular structures of 3-17 were established by single-crystal X-ray diffraction analysis. Electronic structures of the compounds and possible isomers have been examined by DFT calculations.

Redox-Active Ligand-Assisted Two-Electron Oxidative Addition to Gallium(II).

The reaction of digallane (dpp-bian)Ga-Ga(dpp-bian) (2) (dpp-bian=1,2-bis[(2,6-diisopropylphenyl)imino]acenaphthene) with allyl chloride (AllCl) proceeded by a two-electron oxidative addition to afford paramagnetic complexes (dpp-bian)Ga(η1 -All)Cl (3) and (dpp-bian)(Cl)Ga-Ga(Cl)(dpp-bian) (4). Treatment of complex 4 with pyridine induced an intramolecular redox process, which resulted in the diamagnetic complex (dpp-bian)Ga(Py)Cl (5). In reaction with allyl bromide, complex 2 gave metal- and ligand-centered addition products (dpp-bian)Ga(η1 -All)Br (6) and (dpp-bian-All)(Br)Ga-Ga(Br)(dpp-bian-All) (7). The reaction of digallane 2 with Ph3 SnNCO afforded (dpp-bian)Ga(SnPh3 )2 (8) and (dpp-bian)(NCO)Ga-Ga(NCO)(dpp-bian) (9). Treatment of GaCl3 with (dpp-bian)Na in diethyl ether resulted in the formation of (dpp-bian)GaCl2 (10). Diorganylgallium derivatives (dpp-bian)GaR2 (R=Ph, 11; tBu, 14; Me, 15; Bn, 16) and (dpp-bian)Ga(η1 -All)R (R=nBu, 12; Cp, 13) were synthesized from complexes 3, 10, Bn2 GaCl, or tBu2 GaCl by salt metathesis. The salt elimination reaction between (dpp-bian)GaI2 (17) and tBuLi was accompanied by reduction of both the metal and the dpp-bian ligand, which resulted in digallane 2 as the final product. Similarly, the reaction of complex 10 with MentMgCl (Ment=menthyl) proceeded with reduction of the dpp-bian ligand to give the diamagnetic complex [(dpp-bian)GaCl2 ][Mg2 Cl3 (THF)6 ] (18). Compounds 11, 12, 13, 15, and 16 were thermally robust, whereas compound 14 decomposed when heated at reflux in toluene to give complex (dpp-bian-tBu)GatBu2 (19). Both complexes 7 and 19 contain R-substituted dpp-bian ligand: in the former compound the allyl group was attached to the imino-carbon atom, whereas in complex 19, the tBu group was situated on the naphthalene ring. Crystal structures of complexes 3, 8, 9, 10, 13, 14, 18, and 19 were determined by single-crystal X-ray analysis. The presence of dpp-bian radical anions in 3, 6, 8, and 10-16 was determined by ESR spectroscopy.

Gallium Hydrides with a Radical-Anionic Ligand.

The reaction of Cl2GaH with a sodium salt of the dpp-Bian radical-anion (dpp-Bian•-)Na (dpp-Bian = 1,2-bis[(2,6-diisopropylphenyl)imino]acenaphthene) affords paramagnetic gallane (dpp-Bian•-)Ga(Cl)H (1). Oxidation of (dpp-Bian2-)Ga-Ga(dpp-Bian2-) (2) with N2O results in the dimeric oxide (dpp-Bian•-)Ga(µ2-O)2Ga(dpp-Bian•-) (3). A treatment of the oxide 3 with phenylsilane affords paramagnetic gallium hydrides (dpp-Bian•-)GaH2 (4) and (dpp-Bian•-)Ga{OSi(Ph)H2}H (5) depending on the reagent's stoichiometry. The reaction of digallane 2 with benzaldehyde produces pinacolate (dpp-Bian•-)Ga(O2C2H2Ph2) (6). In the presence of PhSiH3, the reaction between digallane 2 and benzaldehyde (2: PhSiH3: PhC(H)O = 1:4:4) affords compound 4. The newly prepared complexes 1, 3-6 consist of a spin-labeled diimine ligand-dpp-Bian radical-anion. The presence of the ligand-localized unpaired electron allows the use of the ESR spectroscopy for characterization of the gallium hydrides reported. The molecular structures of compounds 1, 3-6 have been determined by the single-crystal X-ray analysis.

Synthesis and biological activity of N-substituted-tetrahydro-γ-carbolines containing peptide residues.

The synthesis of novel peptide conjugates of N-substituted-tetrahydro-γ-carbolines has been performed using the sequence of the Ugi multicomponent reaction and Cu(I)-catalyzed click chemistry. The effect of obtained γ-carboline-peptide conjugates on the rat liver mitochondria was evaluated. It was found that all compounds in the concentration of 30 µM did onot induce depolarization of mitochondria but possessed some inhibitory effect on the mitochondria permeability transition. The original N-substituted-tetrahydro-γ-carbolines containing an terminal alkyne group demonstrated a high prooxidant activity, whereas their conjugates with peptide fragments slightly inhibited both autooxidation and the t-BHP-induced lipid peroxidation.

Transcriptional read through interrupts boundary function in Drosophila.

In higher eukaryotes enhancer-promoter interactions are known to be restricted by the chromatin insulators/boundaries that delimit topologically associated domains (TADs); however, there are instances in which enhancer-promoter interactions span one or more boundary elements/TADs. At present, the mechanisms that enable cross-TAD regulatory interaction are not known. In the studies reported here we have taken advantage of the well characterized Drosophila Bithorax complex (BX-C) to study one potential mechanism for controlling boundary function and TAD organization. The regulatory domains of BX-C are flanked by boundaries which function to block crosstalk with their neighboring domains and also to support long distance interactions between the regulatory domains and their target gene. As many lncRNAs have been found in BX-C, we asked whether transcriptional readthrough can impact boundary function. For this purpose, we took advantage of two BX-C boundary replacement platforms, Fab-7 attP50 and F2 attP , in which the Fab-7 and Fub boundaries, respectively, are deleted and replaced with an attP site. We introduced boundary elements, promoters and polyadenylation signals arranged in different combinations and then assayed for boundary function. Our results show that transcriptional readthrough can interfere with boundary activity. Since lncRNAs represent a significant fraction of Pol II transcripts in multicellular eukaryotes, it is possible that many of them may function in the regulation of TAD organization. Author Summary: Recent studies have shown that much genome in higher eukaryotes is transcribed into non-protein coding lncRNAs. It is though that lncRNAs may preform important regulatory functions, including the formation of protein complexes, organization of functional interactions between enhancers and promoters and the maintenance of open chromatin. Here we examined how transcription from promoters inserted into the Drosophila Bithorax complex can impact the boundaries that are responsible for establishing independent regulatory domains. Surprisingly, we found that even a relatively low level of transcriptional readthrough can impair boundary function. Transcription also affects the activity of enhancers located in BX-C regulatory domains. Taken together, our results raise the possibility that transcriptional readthrough may be a widely used mechanism to alter chromosome structure and regulate gene expression.

Synthesis and testing of trifluoromethyl-containing phosphonate-peptide conjugates as inhibitors of serine hydrolases.

A modification of novel fluorinated organophosphorous compounds containing terminal alkyne group by different azidopeptides via Cu(I)-catalyzed click chemistry has been described. The inhibitor activity of trifluoromethyl-containing methylphosphonates and their peptide-conjugates towards acetylcholinesterase, butyrylcholinesterase, and carboxylesterase has been investigated. It was shown that the incorporation of peptide fragments significantly modulates the esterase profile of starting methylphosphonates.

Molecular dynamics simulation of liquid methanol. II. Unified assignment of infrared, Raman, and sum frequency generation vibrational spectra in methyl C-H stretching region.

Vibrational spectra of methyl C-H stretching region are notoriously complicated, and thus a theoretical method of systematic assignment is strongly called for in condensed phase. Here we develop a unified analysis method of the vibrational spectra, such as infrared (IR), polarized and depolarized Raman, and ssp polarized sum frequency generation (SFG), by flexible and polarizable molecular dynamics simulation. The molecular model for methanol has been developed by charge response kernel model to allow for analyzing the methyl C-H stretching vibrations. The complicated spectral structure by the Fermi resonance has been unraveled by empirically shifting potential parameters, which provides clear information on the coupling mechanism. The analysis confirmed that for the IR, polarized Raman, and SFG spectra, two-band structure at about 2830 and 2950 cm(-1) results from the Fermi resonance splitting of the methyl C-H symmetric stretching and bending overtones. In the IR spectrum, the latter, higher-frequency band is overlapped with prominent asymmetric C-H stretching bands. In the depolarized Raman spectrum, the high frequency band at about 2980 cm(-1) is assigned to the asymmetric C-H stretching mode. In the SFG spectrum, the two bands of the splitted symmetric C-H stretching mode have negative amplitudes of imaginary nonlinear susceptibility χ(2), while the higher-frequency band is partly cancelled by positive imaginary components of asymmetric C-H stretching modes.

Molecular dynamics simulation of liquid methanol. I. Molecular modeling including C-H vibration and Fermi resonance.

A flexible and polarizable methanol model has been developed on the basis of charge response kernel (CRK) theory. The present CRK methanol model well reproduces bulk liquid and interfacial properties, including density, enthalpy of vaporization, diffusion coefficient, surface tension, and radial distribution functions. The modeling of intramolecular potential incorporates the anharmonic coupling effects pertinent to the Fermi resonance of stretching and bending overtones, with its effective quantum correction. Therefore, the present methanol model can describe the vibrational spectroscopic features of infrared, Raman, and sum frequency generation spectra of C-H or C-D stretching region of methanol or deuterated methanol on the same footing. This model allows for further detailed analysis of C-H vibrations of alkyl moieties by molecular dynamics simulation.

Influence of the quick-to-court gene deletion on courtship behaviour of Drosophila melanogaster.

Using an original method, we have received Drosophila melanogaster with a deficiency including a complete sequence of quick-to-court gene. In this report, we describe the behavioural features of this new deletion mutant. There were no serious deviations from the normal mating behaviour in flies with the deletion, but the behaviour of deletion mutants still had some features. Of all the elements, only the frequency of licking significantly increased in mutants. The duration of mating elements did not change in flies with deletion, and the latent period decreased only for following the female and licking. We have found that mutant males produce more courtship song than control males when courting Oregon R females as estimated by the pulse song index. In our experiment, mutant females provoked much less pulse song production by Oregon R males than control females do. Moreover, Oregon R males initiate courtship song towards mutant females later than towards control females. In other words, the study of pulse song production showed that the deficiency in females leads to a decrease in the intensity of courtship of wild-type males, whereas the deficiency in males leads to more intensive care for wild-type females.

Low-coordinate Sm(II) and Yb(II) complexes derived from sterically-hindered 1,2-bis(imino)acenaphthene (ArBIG-bian).

Reduction of ArBIG-bian (1, 1,2-bis[(2,6-dibenzhydryl-4-methylphenyl)imino]acenaphthene) with an excess of samarium in tetrahydrofuran (thf) and crystallization of the crude product from a thf/toluene mixture affords [(ArBIG-bian)Sm]·C7H8 (2a), which is free of the coordinating solvent. The use of 1,2-dimethoxyethane (dme) as the reaction medium resulted in the same product, [(ArBIG-bian)Sm]·C4H10O2 (2b), which differs from 2a only in the crystal lattice solvent. Reduction of 1 with an excess of ytterbium in dme gives compound [(ArBIG-bian)Yb(dme)]·2.5C7H8 (3), containing a coordinated dme molecule. All three products consist of dianionic ArBIG-bian ligands whose bulky 2,6-(Ph2CH)2-4-Me-C6H2 groups shield effectively the metal atoms. The newly prepared compounds 2a, 2b and 3 were characterized by 1H NMR and IR spectroscopy. The molecular structures of complexes 2a, 2b and 3 have been established by single crystal X-ray analysis. The intramolecular interactions were analysed on the basis of DFT calculations. The temperature dependence of the magnetic susceptibility of 2b and 3 in the region of 2-300 K was studied. The magnetic moments of complex 2b correspond to divalent samarium.

The insulator functions of the Drosophila polydactyl C2H2 zinc finger protein CTCF: Necessity versus sufficiency.

In mammals, a C2H2 zinc finger (C2H2) protein, CTCF, acts as the master regulator of chromosomal architecture and of the expression of Hox gene clusters. Like mammalian CTCF, the Drosophila homolog, dCTCF, localizes to boundaries in the bithorax complex (BX-C). Here, we have determined the minimal requirements for the assembly of a functional boundary by dCTCF and two other C2H2 zinc finger proteins, Pita and Su(Hw). Although binding sites for these proteins are essential for the insulator activity of BX-C boundaries, these binding sites alone are insufficient to create a functional boundary. dCTCF cannot effectively bind to a single recognition sequence in chromatin or generate a functional insulator without the help of additional proteins. In addition, for boundary elements in BX-C at least four binding sites for dCTCF or the presence of additional DNA binding factors is required to generate a functional insulator.

Synthesis of organophosphates with fluorine-containing leaving groups as serine esterase inhibitors with potential for Alzheimer disease therapeutics.

Acetylcholinesterase and butyrylcholinesterase inhibitors are potential cognition enhancers in Alzheimer disease. O,O-Dialkylphosphate inhibitors with 1-substituted 2,2,2-trifluoroethoxy leaving groups were synthesized by phosphonate-phosphate rearrangement. Substituents in the 1-position of the leaving group along with the O-alkyl groups modulated potency and selectivity against acetylcholinesterase, butyrylcholinesterase, and carboxylesterase.

Pharmacological Sequestration of Mitochondrial Calcium Uptake Protects Neurons Against Glutamate Excitotoxicity.

Neuronal excitotoxicity which is induced by exposure to excessive extracellular glutamate is shown to be involved in neuronal cell death in acute brain injury and a number of neurological diseases. High concentration of glutamate induces calcium deregulation which results in mitochondrial calcium overload and mitochondrial depolarization that triggers the mechanism of cell death. Inhibition of mitochondrial calcium uptake could be potentially neuroprotective but complete inhibition of mitochondrial calcium uniporter could result in the loss of some physiological processes linked to Ca2+ in mitochondria. Here, we found that a novel compound, TG-2112x, can inhibit only the lower concentrations mitochondrial calcium uptake (induced by 100 nM-5 µM) but not the uptake induced by higher concentrations of calcium (10 µM and higher). This effect was not associated with changes in mitochondrial membrane potential and cellular respiration. However, a pre-treatment of neurons with TG-2112x protected the neurons against calcium overload upon application of toxic concentrations of glutamate. Thus, sequestration of mitochondrial calcium uptake protected the neurons against glutamate-induced mitochondrial depolarization and cell death. In our hands, TG-2112x was also protective against ionomycin-induced cell death. Hence, low rate mitochondrial calcium uptake plays an underestimated role in mitochondrial function, and its inhibition could protect neurons against calcium overload and cell death in glutamate excitotoxicity.

Conjugates of methylene blue with γ-carboline derivatives as new multifunctional agents for the treatment of neurodegenerative diseases.

We studied the inhibitory activity of methylene blue (MB) γ-carbolines (gC) conjugates (MB-gCs) against human erythrocyte acetylcholinesterase (AChE), equine serum butyrylcholinesterase (BChE), and a structurally related enzyme, porcine liver carboxylesterase (CaE). In addition, we determined the ability of MB-gCs to bind to the peripheral anionic site (PAS) of Electrophorus electricus AChE (EeAChE) and competitively displace propidium iodide from this site. Moreover, we examined the ability of MB-gCs to scavenge free radicals as well as their influence on mitochondrial potential and iron-induced lipid peroxidation. We found that MB-gCs effectively inhibited AChE and BChE with IC50 values in the range 1.73-10.5 µM and exhibited low potencies against CaE (9.8-26% inhibition at 20 µM). Kinetic studies showed that MB-gCs were mixed-type reversible inhibitors of both cholinesterases. Molecular docking results showed that the MB-gCs could bind both to the catalytic active site and to the PAS of human AChE and BChE. Accordingly, MB-gCs effectively displaced propidium from the peripheral anionic site of EeAChE. In addition, MB-gCs were extremely active in both radical scavenging tests. Quantum mechanical DFT calculations suggested that free radical scavenging was likely mediated by the sulfur atom in the MB fragment. Furthermore, the MB-gCs, in like manner to MB, can restore mitochondrial membrane potential after depolarization with rotenone. Moreover, MB-gCs possess strong antioxidant properties, preventing iron-induced lipid peroxidation in mitochondria. Overall, the results indicate that MB-gCs are promising candidates for further optimization as multitarget therapeutic agents for neurodegenerative diseases.

Diethyl [2,2,2-trifluoro-1-phenyl-sulfonyl-amino-1-(trifluoro-meth-yl)eth-yl]phospho-nate.

The title compound, C(13)H(16)F(6)NO(5)PS, is of inter-est with respect to inhibition of serine hydro-lases. Its structure contains a 1.8797 (13) ŠP-C bond and two inter-molecular N-H⋯O=P hydrogen bonds, resulting in centrosymmetric dimers. An intra-molecular N-H⋯O=P hydrogen bond is also present.