Search

Laccase, a multi‐copper oxidase, is limited by its optimal temperature range and isolation costs. To overcome these challenges, we synthesized copper‐doped zeolitic imidazolate framework‐67 (Cu‐doped ZIF‐67) with 16 mol % Cu as an artificial laccase catalyst. The introduced Cu site acts as the phenol oxidation site, and Co‐based ZIF‐67 is the four‐electron oxygen reduction site. Laccase also employs this division of oxidation and reduction sites. Cu‐doped ZIF‐67 demonstrated significant catalytic activity, superior to natural laccase, especially at elevated temperatures, and maintained stability across multiple reaction cycles. These findings suggest that Cu‐doped ZIF‐67 is a robust, reusable alternative for industrial applications requiring high thermal stability and efficient catalysis. [ABSTRACT FROM AUTHOR]

Type‐1 iodothyronine deiodinase (ID‐1) catalyzes the reductive elimination of 5'‐I and 5‐I on the phenolic and tyrosyl rings of thyroxine (T4), respectively. Chemically verifying whether I atoms with different chemical properties undergo deiodination through a common mechanism is challenging. Herein, we report the modeling of ID‐1 using aliphatic diselenide (Se‐Se) and selenenylsulfide (Se‐S) compounds. Mechanistic investigations of deiodination using the ID‐1‐like reagents suggested that the 5'‐I and 5‐I deiodinations proceed via the same mechanism through an unstable intermediate containing a Se⋅⋅⋅I halogen bond between a selenolate anion, reductively produced from Se‐Se (or Se‐S) in the compound, and an I atom in T4. Moreover, imidazolium and thiol groups, which may act as general acid catalysts, promoted the heterolytic cleavage of the C‐I bond in the Se⋅⋅⋅I intermediate, which is the rate‐determining step, by donating a proton to the C atom. [ABSTRACT FROM AUTHOR]

Herein, we report a new tripodal tris‐benzimidazole ligand (Tbim) that structurally mimics the 3‐His coordination environment of certain nonheme mononuclear iron oxygenases. The coordination chemistry of Tbim was explored with iron(II) revealing a diverse set of coordination modes. The aerobic oxidation of biomimetic model substrate diethyl‐2‐phenylmalonate was studied using the Tbim−Fe and Fe(OTf)2. [ABSTRACT FROM AUTHOR]

The complex cation in the title compound, (carbonyl-1κC)(1η5-pentamethylcyclopentadienyl)(μ-2,3,9,10-tetramethyl-1,4,8,11-tetrathiaundeca-2,9-diene-1,11-diido-1κ2S,S′′′:2κ4S,S′,S′′,S′′′)ironnickel(Fe—Ni) hexafluorophosphate, [FeNi(C10H15)(C11H18S4)(CO)]PF6 or [Ni(L′)FeCp*(CO)]PF6, is composed of the nickel complex fragment [Ni(L′)] coordinated as a metalloligand (using S1 and S4) to the [FeCp*(CO)]+ fragment, where (L′)2− is [S—C(Me)=C(Me)—S—(CH2)3—S—C(Me)=C(Me)—S]2− and where Cp*− is cyclo-C5(Me)5− (pentamethylcyclopentadienyl). The ratio of hexafluorophosphate anion per complex cation is 1:1. The structure at 150 K has orthorhombic (Pbcn) symmetry. The atoms of the complex cation are located on general positions (multiplicity = 8), whereas there are two independent hexafluorophosphate anions, each located on a twofold axis (Wyckoff position 4c; multiplicity = 4). The structure of the new dimetallic cation [Ni(L′)FeCp*(CO)]+ can be described as containing a three-legged piano-stool environment for iron [Cp*Fe(CO)`S2'] and an approximately square-planar `S4' environment for Ni. The NiS2Fe diamond-shaped substructure is notably folded at the S—S hinge: the angle between the NiS2 plane and the FeS2 plane normals is 64.85 (6)°. Largely because of this fold, the nickel–iron distance is relatively short, at 2.9195 (8) Å. The structural data for the complex cation, which contains a new unsaturated `S4' ligand (two C=C double bonds), provide an interesting comparison with the known NiFe hydrogenase models containing a saturated `S4'-ligand analogue having the same number of carbon atoms in the ligand backbone, namely with the structures of [Ni(L)FeCp(CO)]+ (as the PF6− salt, CH2Cl2 solvate) and [Ni(L)FeCp*(CO)]+ (as the PF6− salt), where (L)2− is [S—CH2—CH2—S—(CH2)3—S—CH2—CH2—S]2− and Cp− is cyclopentadienyl. The saturated analogues [Ni(L)FeCp(CO)]+ and [Ni(L)FeCp*(CO)]+ have similar Ni—Fe distances: 3.1727 (6), 3.1529 (7) Å (two independent molecules in the unit cell) and 3.111 (5) Å, respectively, for the two complexes, whereas [Ni(L′)FeCp*(CO)]+ described here stands out with a much shorter Ni—Fe distance [2.9196 (8) Å]. Also, [Ni(L)FeCp(CO)]+ and [Ni(L)FeCp*(CO)]+ show interplanar fold angles that are similar between the two: 39.56 (5), 41.99 (5) (independent molecules in the unit cell) and 47.22 (9) °, respectively, whereas [Ni(L′)FeCp*(CO)]+ possesses a much more pronounced fold [64.85 (6)°]. Given that larger fold angles and shorter Ni—Fe distances are considered to be structurally closer to the enzyme, unsaturation in an `S4'-ligand of the type (S—C2—S—C3—S—C2—S)2− seems to increase structural resemblance to the enzyme for structural models of the type [Ni(`S4')FeCpR(CO)]+ (CpR = Cp or Cp*).

Protein disulfide isomerase (PDI) can assist immature proteins to correctly fold by controlling cysteinyl disulfide (SS)‐relating reactions (i. e. SS‐formation, SS‐cleavage, and SS‐isomerization). PDI controls protein quality by suppressing protein aggregation, as well as functions as an oxidative folding catalyst. Following the amino acid sequence of the active center in PDI, basic amino acid conjugates of 1,2‐diselenan‐4‐amine (1), which show oxidoreductase‐ and isomerase‐like activities for SS‐relating reactions, were designed as a novel PDI model compound. By conjugating the amino acids, the diselenide reduction potential of compound 1 was significantly increased, causing improvement of the catalytic activities for all SS‐relating reactions. Furthermore, these compounds, especially histidine‐conjugated one, remarkably suppressed protein aggregation even at low concertation (0.3 mM∼). Thus, it was demonstrated that the conjugation of basic amino acids into 1 simultaneously achieves the enhancement of the redox reactivity and the capability to suppress protein aggregation. [ABSTRACT FROM AUTHOR]

In a previous study, we reported that (S)-1,2-diselenane-4-amine (1) catalyzes oxidative protein folding through protein disulfide isomerase (PDI)-like catalytic mechanisms and that the direct conjugation of a basic amino acid (Xaa: His, Lys, or Arg) via an amide bond improves the catalytic activity of 1 by increasing its diselenide (Se–Se) reduction potential (E′°). In this study, to modulate the Se–Se redox properties and the association of the compounds with a protein substrate, new catalysts, in which a Gly spacer was inserted between 1 and Xaa, were synthesized. Exhaustive comparison of the PDI-like catalytic activities and E′° values among 1, 1-Xaa, and 1-Gly-Xaa showed that the insertion of a Gly spacer into 1-Xaa either did not change or slightly reduced the PDI-like activity and the E′° values. Importantly, however, only 1-Gly-Arg deviated from this generality and showed obviously increased E°′ value and PDI-like activity compared to the corresponding compound with no Gly spacer (1-Arg); on the contrary, its catalytic activity was the highest among the diselenide compounds employed in this study, while this abnormal enhancement of the catalytic activity of 1-Gly-Arg could not be fully explained by the thermodynamics of the Se–Se bond and its association ability with protein substrates.

Graphical abstract Oxido-alcoholato- and oxido-thiolato-molybdenum(VI) complexes are prepared by oxygen atom transfer reaction to the molybdenum(IV) complexes. The reactivity of the thiolate complex is higher than that of the alcoholate complex. Abstract Oxido-alcoholato- and oxido-thiolato-molybdenum(VI) complexes bearing two ene-1,2-dithiolate ligands (cyclohexene-1,2-dithiolate) are prepared as synthetic models of molybdenum(VI) reaction centers of dimethyl sulfoxide reductase family of molybdenum enzymes. These complexes are prepared by oxygen atom transfer from tertiary amine N -oxide (trimethylamine N -oxide and N,N -dimethylaniline N -oxide) to the five-coordinate alcoholato- and thiolato-molybdenum(IV) complexes, and are characterized by UV–vis, cold-spray-ionization mass, resonance Raman, and 1H NMR spectroscopies. The oxygen atom transfer reactions are studied kinetically at a low temperature (−40 °C) to demonstrate that the reactivity of the thiolato-molybdenum(IV) complex is higher than that of alcoholato-molybdenum(IV) complex by about 7 times, and that the oxygen atom transfer reactivity increases with increasing the electron withdrawing ability of the p -substituent of N , N -dimethylaniline N -oxide derivatives. Mechanistic details are discussed based on the reactivity studies. [ABSTRACT FROM AUTHOR]

Basically enzymes are biological catalysts that increase the speed of a chemical reaction without undergoing any permanent chemical change. With the application of Euler's forward scheme, a discrete-time enzyme model is presented. Further investigation related to its qualitative behaviour revealed that discrete-time model shows rich dynamics as compared to its continuous counterpart. It is investigated that discrete-time model has a unique trivial equilibrium point. The local asymptotic behaviour of equilibrium is discussed for discrete-time enzyme model. Furthermore, with the help of the bifurcation theory and centre manifold theorem, explicit parametric conditions for directions and existence of flip and Hopf bifurcations are investigated. Moreover, two existing chaos control methods, that is, Ott, Grebogi and Yorke feedback control and hybrid control strategy, are implemented. In particular, a novel chaos control technique, based on state feedback control is introduced for controlling chaos under the influence of flip and Hopf bifurcations in discrete-time enzyme model. Numerical simulations are provided to illustrate theoretical discussion and effectiveness of newly introduced chaos control method. [ABSTRACT FROM AUTHOR]

Catalyzed oxygen insertion into C-H bonds represents a continuous challenge in chemistry. Particularly, driving this process at ambient temperature and aqueous media represents a "holy grail" in catalysis. We report on the catalyzed cascade transformations of l-tyrosine or l-phenylalanine to dopachrome in the presence of l-ascorbic acid/H2O2 as oxidizing mixture and CuFe-Prussian Blue-like nanoparticles, Fe3O4 nanoparticles or Au nanoparticles as catalysts. The process involves the primary transformation of l-tyrosine to l-DOPA that is further oxidized to dopachrome. The transformation of l-phenylalanine to dopachrome in the presence of CuFe-Prussian Blue-like nanoparticles and l-ascorbic acid/H2O2 involves in the first step the formation of l-tyrosine and, subsequently, the operation of the catalytic oxidation cascade of l-tyrosine to l-DOPA and dopachrome. Electron spin resonance experiments demonstrate that ascorbate radicals and hydroxyl radicals play cooperative functions in driving the different oxygen-insertion processes. In addition, the aerobic elecrocatalyzed oxidation of l-tyrosine to dopachrome in the presence of naphthoquinone-modified Fe3O4 nanoparticles and l-ascorbic acid is demonstrated. In this system, magnetic-field attraction of the naphthoquinone-modified Fe3O4 nanoparticles onto the electrode allows the quinone-mediated electrocatalyzed reduction of O2 to H2O2 (bias potential -0.5 V vs SCE). The electrogenerated H2O2 is then utilized to promote the transformation of l-tyrosine to dopachrome in the presence of l-ascorbic acid and Fe3O4 catalyst. [ABSTRACT FROM AUTHOR]

We previously reported that water-soluble cyclic selenides can mimic the antioxidative function of glutathione peroxidase (GPx) in water through a simple catalytic cycle, in which the selenide (>Se) is oxidized by H2O2 to the selenoxide (>Se=O) and the selenoxide is reduced by a thiol back to the selenide. In methanol, however, the GPx-like activity could not be explained by this simple scenario. To look into the reasons for the unusual behaviors in methanol, monoamino-substituted cyclic selenides with a variable ring size were synthesized, and the intermediates of the catalytic cycle were characterized by means of 77Se-NMR and LC-MS spectroscopies. In water, it was confirmed that the selenide and the selenoxide mainly contribute to the antioxidative function, though a slight contribution from the dihydroxy selenane (>Se(OH)2) was also suggested. In methanol, on the other hand, other active species, such as hydroxyselenonium (>Se+-OH) and hydroxy perhydroxy selenane (>Se(OH)(OOH)), could be generated to build another catalytic cycle. This over-oxidation would be more feasible for amino-substituted cyclic selenides, probably because the ammonium (NH3+) group would transfer a proton to the selenoxide moiety to produce a hydroxyselenonium species in the absence of an additional proton source. Thus, a shift of the major catalytic cycle in methanol would make the GPx-like antioxidative function of selenides perplexing. [ABSTRACT FROM AUTHOR]

Catecholase activity and its mechanistic investigation of a self-assemblying dimeric Cu(II) complex, Cu 2 L 2 , where L is N , N ′-(ethane-1,2-diyldi- o -phenylene)-bis(pyridine-2-carboxamidide), is presented. The complex was constructed by a spontaneous self-assembly of the organic ligand and Cu(II) ion. X-ray crystallography of Cu 2 L 2 (CH 3 OH) 2 ·2CH 3 OH, found that the coordination geometry of the Cu(II) site was a distorted square pyramid and two Cu(II) ions were apart by 6.992 Å. Though the metal centers are distant, Cu 2 L 2 showed high catecholase activity when 3,5-di- tert -butylcatechol (3,5-H 2 dtbc) was treated with Cu 2 L 2 in the presence of air at basic condition with k cat of 720 h −1 in Michaelis–Menten model. Information collected from the UV–vis kinetic, electron paramagnetic resonance (EPR), and high-resolution electrospray ionization mass spectrometry (ESI MS) measurements on the reaction mixtures could lead the suggestion of the mechanistic pathway of the catecholase activity of Cu 2 L 2 in which each Cu(II) site oxidized 3,5-H 2 dtbc to 3,5-di- tert -butyl-1,2-benzosemiquinonate anion radical (3,5-dtbq − ). Subsequently, 3,5-di- tert -butyl- o -quinone (3,5-dtbq) was formed via both disproportionation and air oxidation of 3,5-dtbq − . Cu 2 L 2 could be reduced to either one- or two-electron reduced state. The reduced complexes were reoxidized by dioxygen molecule accompanying with the generation of hydrogen peroxide. [ABSTRACT FROM AUTHOR]

The enzyme model (EM), inspired by biological enzyme catalysis, is a computational-functional description of information processing and distribution in modular cognitive systems. It has been argued that EM offers advantages in solving both the allocation problem and global computation and thus may play a role in upholding the massive modularity hypothesis (MMH). This paper, however, argues that EM solutions are untenable, as EM avoids the infinite regress of allocation problem only at a high cost and with several critical drawbacks. Moreover, to clarify global processes, EM needs to satisfy two necessary conditions: first to demonstrate that the EM allows cross module communication, and second to be sensitive to not only the syntax but also the semantics of representations. I argue that EM only satisfies the first condition and thus fails to hold. [ABSTRACT FROM AUTHOR]

Abstract: To mimick the natural enzymes [FeFe]-hydrogenases, some new porphyrin and metalloporphyrin moiety-containing model complexes, namely 5-[p-Fe2(CO)6(μ-SCH2)2CHO2CC6H4],10,15,20-triphenylporphyrin (2), 5-[p-Fe2(CO)6(μ-SCH2)2CHO2CC6H4],10,15,20-triphenylporphyrinozinc (3), 5-[p-Fe2(CO)6(μ-SCH2)2NC2H4SC6H4],10,15,20-triphenylporphyrin (7), and 5-[p-Fe2(CO)5(μ-SCH2)2NC2H4SC6H],10,15,20-triphenylporphyrin (8), have been successfully prepared by our designed synthetic routes involving the corresponding precursor compounds [(μ-SCH2)2CHO2CC6H4CHO-p]Fe2(CO)6 (1), p-Boc-NHC2H4SC6H4CHO (4), 5-(p-Boc-NHC2H4SC6H4),10,15,20-triphenylporphyrin (5), and 5-(p-NH2C2H4 SC6H4),10,15,20-triphenylporphyrin (6). All these new compounds 1–8 have been characterized by elemental analysis and various spectroscopic methods, and particularly for 1–3 and 7 by X-ray crystallography. In addition, the density functional theory computations on 8 were performed to assist its structural characterization. [Copyright &y& Elsevier]

A Ni(II)-mixed-chalcogenolate carbonyl complex, [PPN][Ni(CO)(SePh)2(S- p-C6H4-Cl)] ( 1) was obtained from the treatment of [CpNi(μ-S- p-C6H4-Cl)]2 and fac-[PPN][Fe(CO)3(SePh)3]. Using 1 as a precursor, two four-coordinated square planar Ni(II)-chalcogenolate/chalcogenol complexes, [PPN][Ni-(SePh)(N(CH2CH2S)2(CH2CH2SH))] ( 2) and [Ni(PEt3)(N(CH2CH2S)2(CH2CH2SH))] ( 4) containing the thiol in the secondary coordination sphere have been synthesized and identified by single-crystal X-ray diffraction. Analyses of structural data and vibrational energy (νSH = 2431 cm−1 for 4) reveal that the pendant thiol in complexes 2 and 4, respectively do not form intramolecular interaction with the nickel and thiolato sulfur. Compared to previously reported analogues coordinated by [P( o-C6H4S)2( o-C6H4SH)]2−ligand (Chen, C.-H.; Lee, G.-H.; Liaw, W.-F. Inorg. Chem. 2006, 45, 2307), the lack of intramolecular interaction in complexes 2 and 4 may be attributed to the rotatable C-S and C-C bonds of [N(CH2CH2S)2(CH2CH2SH)]2− ligand, precluding the pendant thiol from pointing a direction to the nickel and thiolato sulfur. [ABSTRACT FROM AUTHOR]

Peptide dendrimers composed of alternating sequences of natural amino acids and branching diamino acids are investigated as synthetic enzyme models. The dendrimers can be prepared by solid-phase peptide synthesis and are obtained pure in yields of 5–35%. Peptide dendrimers with surface histidine residues catalyze ester hydrolysis reaction with enzyme-like kinetics, including substrate binding (KM), catalytic turnover (kcat), and rate acceleration kcat/kuncat = 1000–20'000. Mechanistic investigation by substrate variation, pH-profile, and isothermaltitration calorimetry show that the catalytic effect is caused by positive interaction between the histidine side-chains and creation of a hydrophobic microenvironment for substrate binding.

An efficient and selective four-electron plus four-proton (4e-/4H+) reduction of O2 to water by decamethylferrocene and trifluoroacetic acid can be catalyzed by a synthetic analog of the heme a3/CuB site in cytochrome c oxidase (6LFeCu) or its Cu-free version (6LFe) in acetone. A detailed mechanistic-kinetic study on the homogeneous catalytic system reveals spectroscopically detectable intermediates and that the rate-determining step changes from the O2-binding process at 25?°C room temperature (RT) to the O-O bond cleavage of a newly observed FeIII-OOH species at lower temperature (-60 °C). At RT, the rate of O2-binding to 6LFeCu is significantly faster than that for 6LFe, whereas the rates of the O-O bond cleavage of the FeIII-OOH species observed (-60 °C) with either the 6LFeCu or 6LFe catalyst are nearly the same. Thus, the role of the Cu ion is to assist the heme and lead to faster O2-binding at RT. However, the proximate Cu ion has no effect on the O-O bond cleavage of the FeIII-OOH species at low temperature. [ABSTRACT FROM AUTHOR]

Abstract: As the new H-cluster models, six diiron propanedithiolate (PDT) complexes with mono- and diphosphine ligands have been prepared and structurally characterized. The monophosphine model complex (μ-PDT)Fe2(CO)5[Ph2PNH(t-Bu)] (1) was prepared by reaction of parent complex (μ-PDT)Fe2(CO)6 (A) with 1 equiv of Ph2PNH(t-Bu) in refluxing xylene, whereas A reacted with 1 equiv of Me3NO·2H2O in MeCN at room temperature followed by 1 equiv of Ph2PH to give the corresponding monophosphine model complex (μ-PDT)Fe2(CO)5(Ph2PH) (2). Further treatment of 2 with 1 equiv of n-BuLi in THF at −78°C followed by 1 equiv of CpFe(CO)2I from −78°C to room temperature afforded monophosphine model complex (μ-PDT)Fe2(CO)5[Ph2PFe(CO)2Cp] (3), whereas the diphosphine model complexes (μ-PDT)Fe2(CO)4(Ph2PC2H4PPh2) (4), (μ-PDT)Fe2(CO)4[(Ph2P)2N(n-Pr)] (5) and (μ-PDT)Fe2(CO)4[(Ph2P)2N(n-Bu)] (6) were obtained by reactions of A with ca.1 equiv of the corresponding diphosphines in refluxing xylene. All the new model complexes were characterized by elemental analysis, spectroscopy and particularly for 1 and 3–6 by X-ray crystallography. On the basis of electrochemical and spectroelectrochemical studies, model 5 was found to be a catalyst for HOAc proton reduction to H2, and for this electrocatalytic reaction an ECCE mechanism was proposed. [Copyright &y& Elsevier]

Enzymes have fascinated scientists since their discovery and, over some decades, one aim in organic chemistry has been the creation of molecules that mimic the active sites of enzymes and promote catalysis. Nevertheless, even today, there are relatively few examples of enzyme models that successfully perform Michaelis–Menten catalysis under enzymatic conditions (i.e., aqueous medium, neutral pH, ambient temperature) and for those that do, very high rate accelerations are seldomly seen. This review will provide a brief summary of the recent developments in artificial enzymes, so called “Chemzymes”, based on cyclodextrins and other molecules. Only the chemzymes that have shown enzyme-like activity that has been quantified by different methods will be mentioned. This review will summarize the work done in the field of artificial glycosidases, oxidases, epoxidases, and esterases, as well as chemzymes that catalyze conjugate additions, cycloadditions, and self-replicating processes. The focus will be mainly on cyclodextrin-based chemzymes since they have shown to be good candidate structures to base an enzyme model skeleton on. In addition hereto, other molecules that encompass binding properties will also be presented. [ABSTRACT FROM AUTHOR]

Abstract: First examples of tungsten complexes, (Et4N)2[WO(L0)2]((Et4N)2 [1a]) and (Et4N)2[WO2(L0)2]((Et4N)2 [1b]), containing pyranodithiolene were synthesized as new models of reaction center of tungsten enzymes. The complexes were characterized by IR, UV–Vis, Raman spectroscopies, and cyclic voltammogram (CV). The crystal structures were determined by X-ray crystallography. The pyrane ring affected the Wretchings in 1a and 1b, the redox potential of 1a, and LMCT bands of 1b. [Copyright &y& Elsevier]

Two cyclodextrin derivatives (1 and 2) were prepared in an attempt to create glycosidase mimics with a general acid catalyst and a nucleophilic carboxylate group. The catalysts 1 and 2 were found to catalyse the hydrolysis of 4-nitrophenyl β-D-glucopyranoside at pH 8.0, but rapidly underwent decomposition with loss of hydrogen cyanide to convert the cyanohydrin to the corresponding aldehyde. The initial rate of the catalysis shows that the cyanohydrin group in these molecules functions as a good catalyst, but that the carboxylate has no positive effect. The decomposition product aldehydes display little or no catalysis. A mechanism for the decomposition is suggested. [ABSTRACT FROM AUTHOR]

An exhaustive analysis of local and global bifurcations in an enzyme-catalyzed reaction model is carried out. The model, given by a planar five-parameter system of autonomous ordinary differential equations, presents a great richness of bifurcations. This enzyme-catalyzed model has been considered previously by several authors, but they only detected a minimal part of the dynamical and bifurcation behavior exhibited by the system. First, we study local bifurcations of equilibria up to codimension-three (saddle-node, cusps, nondegenerate and degenerate Hopf bifurcations, and nondegenerate and degenerate Bogdanov–Takens bifurcations) by using analytical and numerical techniques. The numerical continuation of curves of global bifurcations allows to improve the results provided by the study of local bifurcations of equilibria and to detect new homoclinic connections of codimension-three. Our analysis shows that such a system exhibits up to sixteen different kinds of homoclinic orbits and thirty different configurations of equilibria and periodic orbits. The coexistence of up to five periodic orbits is also pointed out. Several bifurcation sets are sketched in order to show the dynamical behavior the system exhibits. The different codimension-one and -two bifurcations are organized around five codimension-three degeneracies. [ABSTRACT FROM AUTHOR]

Tris(2-guanidinium-ethyl)amine (1) was prepared as a supramolecular receptor of hydrogen orthovanadate to mimic the active site of vanadium haloperoxidase (V-HPO). Both 1H and 51V NMR titration indicated 1:1 complex (5) formation between (1) with with a binding constant of 1.1×103 M−1. Similar as V-HPO, a UV band at 307 nm was observed upon binding of to (1). According to DFT calculations UV transitions >300 nm observed for both the enzyme and its mimic are due to V–N interactions. [Copyright &y& Elsevier]

Several bis-β-cyclodextrin porphyrins have been prepared as supramolecular receptors of carotenoids. The binding constants of carotenoids to receptors were determined by quenching the fluorescence of the porphyrins on hydrophobic binding of carotenoids within the cavities of cyclodextrins. Ka=8.3×106 M−1 was calculated for binding of β,β-carotene to bis-β-cyclodextrin Zn porphyrin. The corresponding Ru complex catalyzes the central cleavage of carotenoids in the presence of tert-butyl hydroperoxide in a biphasic system. [ABSTRACT FROM AUTHOR]

Intrinsic chemical properties of the zinc(II) ion in zinc enzymes have been investigated by the model of 1 :1 Zn2+-macrocyclic polyamine complexes, including Zn2+-1,5,9-triazacyclododecane ([12]aneN3) and 1,4,7,10-tetraazacyclododecane (cyclen). The physiologically most suitable p Ka values for the Zn2+-bound H2O in enzymes were illustrated by the first model Zn2+-[12]aneN3 complex, which mimics the essential kinetic and thermodynamic roles of Zn2+ in carbonic anhydrase. The activation of proximate serine residues (in alkaline phosphatase) and activation of alcohols for hydride transfer to NAD+ (in alcohol dehydrogenase) were also mimicked by Zn2+-[12]aneN3 complexes. The functions of two zincs in dinuclear metallophosphatases were explained by a new dinuclear Zn2+-cryptate. For an aldolase type II model, a Zn2+-cyclen derivative showed facile enolate formation from a proximate carbonyl pendant under physiological conditions. The strong anion affinities, which Zn2+ intrinsically possesses, were exploited into novel selective nucleobase thymine (or uracil) recognition of Zn2+-cyclen complexes by the strong Zn2+-imido anion bond formation. The Zn2+-aromatic-pendant cyclen complexes selectively bind to T (or U) in single- and double-stranded DNA (or RNA). Thus, Zn2+ complexes act like molecular zippers to break A-T pairs in DNA, which was proven by various physicochemical measurements and DNA footprinting assays. These Zn2+ complexes showed some relevant biochemical and biological properties such as inhibition of transcriptional factor, TATA binding protein, or strong antimicrobial activities to Gram-positive bacterial strains. [ABSTRACT FROM AUTHOR]

Simple Summary: A polypeptide chain, which is a biological polymer composed of amino acids, can have a physiological function as a "protein" by forming a unique three-dimensional structure through protein folding. Structural failure of proteins in cells frequently induces various diseases, such as neurodegenerative diseases and diabetes. Therefore, cells are equipped with various enzymes, such as protein disulfide isomerase (PDI), to promote correct folding and avoid misfolding. In both cells and test tubes, protein folding is a key process in determining the overall efficiency of protein synthesis. Therefore, it is crucial to develop an artificial folding catalyst, which behaves like PDI, for both drug discovery and protein engineering. Herein, we report the structural optimization of a cyclic diselenide molecule to improve its intrinsic PDI-like catalytic activity. In a previous study, we reported that (S)-1,2-diselenane-4-amine (1) catalyzes oxidative protein folding through protein disulfide isomerase (PDI)-like catalytic mechanisms and that the direct conjugation of a basic amino acid (Xaa: His, Lys, or Arg) via an amide bond improves the catalytic activity of 1 by increasing its diselenide (Se–Se) reduction potential (E′°). In this study, to modulate the Se–Se redox properties and the association of the compounds with a protein substrate, new catalysts, in which a Gly spacer was inserted between 1 and Xaa, were synthesized. Exhaustive comparison of the PDI-like catalytic activities and E′° values among 1, 1-Xaa, and 1-Gly-Xaa showed that the insertion of a Gly spacer into 1-Xaa either did not change or slightly reduced the PDI-like activity and the E′° values. Importantly, however, only 1-Gly-Arg deviated from this generality and showed obviously increased E°′ value and PDI-like activity compared to the corresponding compound with no Gly spacer (1-Arg); on the contrary, its catalytic activity was the highest among the diselenide compounds employed in this study, while this abnormal enhancement of the catalytic activity of 1-Gly-Arg could not be fully explained by the thermodynamics of the Se–Se bond and its association ability with protein substrates. [ABSTRACT FROM AUTHOR]

This study developed dipeptide-conjugated 1,2-diselenan-4-amine (1), i. e., 1-Xaa-His, as a new class of S-denitrosylase mimic. The synthesized compounds, especially 1-Pro-His, remarkably promoted S-denitrosylation of nitrosothiols (RSNO) via a catalytic cycle involving the reversible redox reaction between the diselenide and its corresponding diselenol ([SeH,SeH]) form with coexisting reductant thiols (R'SH), during which the [SeH,SeH] form as a key reactive species reduces RSNO to the corresponding thiol (RSH). Structural analyses of 1-Pro-His suggested that the peptide backbone of [SeH,SeH] is rigidly bent to form a γ-turn, possibly including an NH⋅⋅⋅Se hydrogen bond between the imidazole ring of His and selenol group, thus stabilizing the [SeH,SeH] form thermodynamically, and dramatically enhancing the catalytic activity. Furthermore, the synthetic compounds were found to prohibit S-nitrosylation-induced protein misfolding in the presence of RSNO, eventually implying their potential as a drug seed for misfolding diseases caused by the dysregulation of the S-denitrosylation system., (© 2021 Wiley-VCH GmbH.)

Proximity of reactant sites is one of the major factors that contributes to specificity and high reaction rates observed in enzyme catalysis. Enzymes achieve this proximity between the reactant sites by having high affinity for the substrate. Structural studies on enzyme-substrate complexes provide sufficient evidence in this context and indicate that weak bonding interaction are involved in formation of such complexes. We have exploited the hydrophobic interaction between cholesterol and benzophenone to carry out photoinduced remote functionalisation of cholesterol at specific sites. Thus, using polar solvents intramolecular hydrophobic interaction between cholesterol and benzophenone permitted exclusive functionalisation of ring D in cholesterol. The current study indicates that weak interactions between the reactants can be used to bring them in proximity and photochemical reactions can provide the method for functionalising even inert sites like C-H bonds. [ABSTRACT FROM AUTHOR]

Amphiphilic derivatives of (±)- trans -1,2-diselenane-4,5-diol (DSTox) decorated with long alkyl chains or aromatic substituents via ester linkages were applied as glutathione peroxidase (GPx)-like catalysts. The reduction of H 2 O 2 with the diselenide catalysts was accelerated through a GPx-like catalytic cycle, in which the diselenide (Se–Se) bond was reduced to the diselenolate form ([Se-,Se-) by coexisting dithiothreitol, and the generated highly active [Se-,Se- subsequently reduced H 2 O 2 to H 2 O retrieving the original Se–Se form. In the lipid peroxidation of lecithin/cholesterol liposomes induced by 2,2′-azobis(2-amidinopropane) dihydrochloride (AAPH), on the other hand, the Se–Se form directly reduced lipid peroxide (LOOH) to the corresponding alcohol (LOH), inhibiting the radical chain reaction, to exert the antioxidative effect. Thus, the two GPx-like catalytic cycles can be switched depending on the peroxide substrates. Furthermore, hydrophilic compounds with no or short alkyl groups (C3) showed high antioxidative activities for the catalytic reduction of H 2 O 2 , while lipophilic compounds with long alkyl chains (C6-C14) or aromatic substituents were more effective antioxidants against lipid peroxidation. In addition, these compounds showed low cytotoxicity in cultured HeLa cells and exhibited sufficient anti-lipid peroxidative activities, suggesting their potentials as selenium-based antioxidative drugs. [ABSTRACT FROM AUTHOR]