Thermodynamic Parameters for the Association of Fluorinated Benzenesulfonamides with Bovine Carbonic Anhydrase II

This paper describes a calorimetric study of the association of a series of seven fluorinated benzenesulfonamide ligands (C₆H_nF_5?nSO₂NH₂) with bovine carbonic anhydrase II (BCA). Quantitative structure–activity relationships between the free energy, enthalpy, and entropy of binding and pK_a and log P of the ligands allowed the evaluation of the thermodynamic parameters in terms of the two independent effects of fluorination on the ligand: its electrostatic potential and its hydrophobicity. The parameters were partitioned to the three different structural interactions between the ligand and BCA: the Zn^II cofactor–sulfonamide bond (≈65 % of the free energy of binding), the hydrogen bonds between the ligand and BCA (≈10 %), and the contacts between the phenyl ring of the ligand and BCA (≈25 %). Calorimetry revealed that all of the ligands studied bind in a 1:1 stoichiometry with BCA; this result was confirmed by ¹⁹F NMR spectroscopy and X‐ray crystallography (for complexes with human carbonic anhydrase II).     

Catalysis and Electron Transfer in De Novo Designed Helical Scaffolds

The relationship between protein structure and function is one of the greatest puzzles within biochemistry. De novo metalloprotein design is a way to wipe the board clean and determine what is required to build in function from the ground up in an unrelated structure. This Review focuses on protein design efforts to create de novo metalloproteins within alpha‐helical scaffolds. Examples of successful designs include those with carbonic anhydrase or nitrite reductase activity by incorporating a ZnHis₃ or CuHis₃ site, or that recapitulate the spectroscopic properties of unique electron‐transfer sites in cupredoxins (CuHis₂Cys) or rubredoxins (FeCys₄). This work showcases the versatility of alpha helices as scaffolds for metalloprotein design and the progress that is possible through careful rational design. Our studies cover the invariance of carbonic anhydrase activity with different site positions and scaffolds, refinement of our cupredoxin models, and enhancement of nitrite reductase activity up to 1000‐fold.     

Cross-Talks Between Sulfane Sulfur and Thiol at a Zinc(II) Site

Transformations of sulfane sulfur compounds (e. g. organic polysulfides (R−S_n−R, n>2) and elemental sulfur (S₈)) play pivotal roles in the biochemical landscape of sulfur, and thus supports signaling activities of H₂S. Although a number of previous reports illustrate amine mediated reactions of S₈ and thiol (RSH) yielding R−S_n−R, this report illustrates that a tripodal [Zn^II] complex [( Bn₃Tren )Zn^II−OH₂](ClO₄)₂ ( 1 ) facilitates the reactions of sulfane sulfur and thiol (RSH), thereby offering an amine-free biologically relevant complementary route. UV-vis monitoring of the reactions and a set of control experiments underline the definitive role of [Zn^II] coordination motif in the reactions of sulfane sulfur (e. g. S₈ and R−S_n−R) with RSH. Detailed investigations (UV-vis, NMR, ESI-MS, intermediate trapping, and TEMPO radical interference experiments) disclose the key differences in the [Zn^II] versus previously known amine mediated routes. Moreover, the persulfide (RSS⁻) trapping experiments using 1-fluoro-2,4-dinitrobenzene (F-DNB) reveal the intermediacy of RSS⁻ species in the [Zn^II] mediated reactions of sulfane sulfur and thiol, thereby demonstrating [Zn^II] assisted persulfidation of thiol in the presence of sulfane sulfur species. Of broader impact, this study underscores the feasible influence of biologically relevant [Zn^II] coordination motifs (e. g. carbonic anhydrase) on the sulfane sulfur chemistry in biology.     

Metal(II) Ion Complexes with 5‐(Pyrazin‐2‐yl)‐2,4‐dihydro‐3H‐1,2,4‐triazole‐3‐thione; Synthesis,Structural Characterization,Acid‐base,and Complexing Properties in Solution

The study reports the synthesis of complexes Co(HL)Cl₂ ( 1 ), Ni(HL)Cl₂ ( 2 ), Cu(HL)Cl₂ ( 3 ), and Zn(HL)₃Cl₂ ( 4 ) with the title ligand, 5‐(pyrazin‐2‐yl)‐1,2,4‐triazole‐5‐thione (HL), and their characterization by elemental analyses, ESI‐MS (m/z), FT‐IR and UV/Vis spectroscopy, as well as EPR in the case of the Cu^II complex. The comparative analysis of IR spectra of the metal ion complexes with HL and HL alone indicated that the metal ions in 1 , 2 , and 3 are chelated by two nitrogen atoms, N(4) of pyrazine and N(5) of triazole in the thiol tautomeric form, whereas the Zn^II ion in 4 is coordinated by the non‐protonated N(2) nitrogen atom of triazole in the thione form. pH potentiometry and UV/Vis spectroscopy were used to examine Co^II, Ni^II, and Zn^II complexes in 10/90 (v/v) DMSO/water solution, whereas the Cu^II complex was examined in 40/60 (v/v) DMSO/water solution. Monodeprotonation of the thione triazole in solution enables the formation of the L:M = 1:1 species with Co^II, Ni^II and Zn^II, the 2:1 species with Co^II and Zn^II, and the 3:1 species with Zn^II. A distorted tetrahedral arrangement of the Cu^II complex was suggested on the basis of EPR and Vis/NIR spectra.     

Directly 2,12‐ and 2,8‐Linked ZnII Porphyrin Oligomers: Synthesis,Optical Properties,and Coherence Lengths

Directly 2,12‐ and 2,8‐linked Zn^II porphyrin oligomers were prepared from 2,12‐ and 2,8‐diborylated Zn^II porphyrin by a cross platinum‐induced coupling with a 2‐borylated Zn^II porphyrin end unit followed by a triphenylphosphine (PPh₃)‐mediated reductive elimination. Comparative studies on the steady‐state absorption and fluorescence spectra and the fluorescence lifetimes led to a conclusion that the exciton in the S₁ state is delocalized over approximately four and two Zn^II porphyrin units for 2,12‐ and 2,8‐linked Zn^II porphyrin arrays, respectively.     

Two Disparate 2‐fold Interpenetrating Frameworks Constructed from ZnII, 4,4′‐Dipyridyl Disulfide and Maleic/ Fumaric Acid

The reaction of Zn^II nitrate with maleic acid (H₂mal) / fumaric acid (H₂fum) and 4,4′‐dipyridyl disulfide (4‐pds) resulted under same conditions in two distinct interpenetrated compounds, namely [Zn(4‐dps)₂(H₂O)₂]·2Hmal ( 1 ) and [Zn(4‐dps)(fum)] ( 2 ). In 1 , Hmal anion adopts bridging mode based on hydrogen bonding, affording a 2‐fold parallel interpenetrated 3D→3D α‐Po net hydrogen‐bonded framework, in which 1D double‐stranded chains are formed, and then extended to a 3D supramolecular architecture combining second‐sphere hydrogen‐bonded interactions. For 2 , fum dianion takes on bis‐dentate bridging coordination fashion, furnishing a 2‐fold interpenetrated 2D→2D (4,4) layered coordination network, in which the tetrahedral Zn^II atoms are interlinked by 4‐dps and fum. Additionally, the compound 2 shows strong fluorescence in the solid state at room temperature.     

Zinc Transfer Kinetics of Metallothioneins and Their Fragments with Apo‐carbonic Anhydrase

The zinc transfer reactions from Zn₇‐MT‐I, Zn₇‐MT‐II, Zn₄‐α fragment (MT‐I) and Zn₄,‐α fragment (MT‐II) to apo‐carbonic anhydrase have been studied. In each reaction, no more than one zinc ion per molecule is involved in metal transfer. Zn₇‐MT‐I and Zn₇‐MT‐II donate zinc to apo‐carbonic anhydrase and de novo constitute it at a comparable efficiency, while Zn₇‐MT‐II exhibits a little faster rate. Surprisingly, Zinc is released from Zn₄‐α fragment (MT‐II) with a much faster rate than from Zn₄‐α fragment (MT‐I), whose rate is close to that of Zn₇‐MT‐I. The reason for the difference is still unknown. Introducing complex compounds into this system may give rise to an effect on the reaction. The transfer from Zn₇‐MT‐II in the presence of reduced glutathione shows little difference compare to the control, suggesting that the reduced glutathione is not involved in zinc transfer process. However, glutathione disulfide does accelerate this zinc transfer reaction remarkably, indicating that the oxidative factors contribute to zinc release from metallothioneins.     

Kinetics and mechanism of the catalytic dehydration of HCO3− by zinc(II) complexes of tripod ligands

The kinetics of the catalyzed dehydration of HCO₃^? by zinc(II) containing tripod complexes has been studied at 25°C using the stopped‐flow technique. The direction of reaction curve was changed in aqueous solution when the pH of the solution was greater than 7.5. The pH‐profile of rates of the dehydration reactions indicates that only the aqua complex catalyzes the dehydration of HCO₃^? via a ligand substitution process. The second‐order rate constants for the dehydration of HCO₃^? catalyzed by complexes Zn₃L1, Zn₃L2, Zn₃L3, and Zn₃L4 are 0.96, 2.53, 12.05, and 6.99 mol^?1 dm³ s^?1 respectively. At the same time, the pK_a values 7.60, 7.16, 7.51, and 7.42 for the deprotonation of the Zn(II)‐bound water in the four catalysts were obtained, which are consistent with those that resulted from pH titrations, i.e. 7.47, 7.25, 7.52, and 7.38 respectively. The mechanism is proposed and the results are compared with other model complexes of carbonic anhydrase. © 2004 Wiley Periodicals, Inc. Int J Chem Kinet 36: 197–203, 2004     

Syntheses,Structures and Spectral Properties of Mononuclear CuII and Dimeric ZnII Complexes Based on an Asymmetric Salamo‐type N2O2 Ligand

The asymmetric Salamo‐type N₂O₂ ligand H₂L and its corresponding Cu^II and Zn^II complexes [CuL] and [{ZnL}₂]·2CH₃CN were synthesized and structurally characterized. Crystallographic data of the Cu^II complex revealed that the Cu^II ion is tetracoordinate with a slightly distorted square planar arrangement forming a 2D supramolecular plane structure by hydrogen bonding and π···π stacking interactions. In the Zn^II complex, the Zn^II ions are pentacoordinate in N₂O₂ tetradentate fashion and intermolecular contacts between Zn^II and oxygen atoms result in a head‐to‐tail dimer. The Zn^II ions were found to have slightly distorted square pyramidal and trigonal bipyramidal arrangements, respectively. Hydrogen bonding interactions stabilized the Zn^II complex to facilitate self‐assembly to a 1D linear chain. The Cu^II and Zn^II complexes show intense photoluminescence with maximum emissions at approx. 426 and 411 nm upon excitation at 360 and 350 nm, respectively.     

Unexpected Macrocyclic Multinuclear Zinc and Nickel Complexes that Function as Multitasking Catalysts for CO2 Fixations

Unique self‐assembled macrocyclic multinuclear Zn^II and Ni^II complexes with binaphthyl‐bipyridyl ligands (L) were synthesized. X‐ray analysis revealed that these complexes consisted of an outer ring (Zn₃L₃ or Ni₃L₃) and an inner core (Zn₂ or Ni). In the Zn^II complex, the inner Zn₂ part rotated rapidly inside the outer ring in solution on an NMR timescale. These complexes exhibited dual catalytic activities for CO₂ fixations: synthesis of cyclic carbonates from epoxides and CO₂ and temperature‐switched N‐formylation/N‐methylation of amines with CO₂ and hydrosilane.     

Fluorescent and Electrochemical Sensing of Polyphosphate Nucleotides by Ferrocene Functionalised with Two ZnII(TACN)(pyrene) Complexes

The [Fc? bis{Zn^II(TACN)(Py)}] complex, comprising two Zn^II(TACN) ligands (Fc=ferrocene; Py=pyrene; TACN=1,4,7‐triazacyclononane) bearing fluorescent pyrene chromophores linked by an electrochemically active ferrocene molecule has been synthesised in high yield through a multistep procedure. In the absence of the polyphosphate guest molecules, very weak excimer emission was observed, indicating that the two pyrene‐bearing Zn^II(TACN) units are arranged in a trans‐like configuration with respect to the ferrocene bridging unit. Binding of a variety of polyphosphate anionic guests (PPi and nucleotides di‐ and triphosphate) promotes the interaction between pyrene units and results in an enhancement in excimer emission. Investigations of phosphate binding by ³¹P NMR spectroscopy, fluorescence and electrochemical techniques confirmed a 1:1 stoichiometry for the binding of PPi and nucleotide polyphosphate anions to the bis(Zn^II(TACN)) moiety of [Fc? bis{Zn^II(TACN)(Py)}] and indicated that binding induces a trans to cis configuration rearrangement of the bis(Zn^II(TACN)) complexes that is responsible for the enhancement of the pyrene excimer emission. Pyrophosphate was concluded to have the strongest affinity to [Fc? bis{Zn^II(TACN)(Py)}] among the anions tested based on a six‐fold fluorescence enhancement and 0.1 V negative shift in the potential of the ferrocene/ferrocenium couple. The binding constant for a variety of polyphosphate anions was determined from the change in the intensity of pyrene excimer emission with polyphosphate concentration, measured at 475 nm in CH₃CN/Tris‐HCl (1:9) buffer solution (10.0 mM , pH 7.4). These measurements confirmed that pyrophosphate binds more strongly (K_b=(4.45±0.41)×10⁶ M ^?1) than the other nucleotide di‐ and triphosphates (K_b=1–50×10⁵ M ^?1) tested.     

A three‐dimensional coordination polymer of 3‐(3,5‐dicarboxybenzyloxy)benzoic acid with zinc

The synthesis is reported of the tricarboxylic acid 3‐(3,5‐dicarboxybenzyloxy)benzoic acid (H₃L) and the product of its reaction under solvothermal conditions with Zn^II cations, namely poly[[μ₆‐3‐(3,5‐dicarboxylatobenzyloxy)benzoato](dimethylformamide)‐μ₃‐hydroxido‐dizinc(II)], [Zn₂(C₁₆H₉O₇)(OH)(C₃H₇NO)]_n, the formation of which is associated with complete deprotonation of H₃L. Its crystal structure consists of a single‐framework coordination polymer of the organic L³⁻ ligand with Zn^II cations in a 1:2 ratio, with additional hydroxide and dimethylformamide (DMF) ligands coordinated to the Zn^II centres. The Zn^II cations are characterized by coordination numbers of 5 and 6, being bridged to each other by hydroxide ligands. In the polymeric framework, the carboxylate‐ and hydroxy‐bridged Zn^II cations are arranged in coordination‐tessellated columns, which propagate along the a axis of the crystal structure, and each L³⁻ ligand links to seven different Zn^II centres via Zn—O bonds of two different columns. The coordination framework, composed of [Zn₂(L)(OH)(DMF)]_n units, forms an open architecture, the channel voids within it being filled by the zinc‐coordinating DMF ligands. This report provides the first structural evidence for the formation of coordination polymers with H₃L via multiple metal–ligand bonds through its carboxylate groups.<!?tpb=21.5pt>     

Selective Coordination of Gallium(III), Zinc(II), and Copper(II) by an Asymmetric Dinucleating Ligand: A Model for Metallophosphatases

Complexation studies of the dinucleating ligand H₃L (H₃L=2‐{[bis(pyridin‐2‐ylmethyl)amino]methyl}‐6‐{[bis(6‐pivaloylamidopyridin‐2‐ylmethyl)amino]methyl}‐4‐methylphenol), with metal‐binding sites A and B, which both provide four donors to a metal ion; a tertiary amine; two pyridines (substituted with amide hydrogen‐bond donors in site B), and a bridging phenolate, with Zn^II, Cu^II, and Ga^III are reported. The titration of H₃L with the three metal ions in solution was monitored by NMR spectroscopy or EPR and UV/Vis/near‐IR spectroscopy, as well as by ESI‐MS to analyze the selectivity of the two metal‐ion sites A and B of this model ligand for metallophosphatases; the spectroscopic assignments are supported by X‐ray crystallography results. The first Zn^II ion coordinates to site A with unsubstituted pyridine donors and, upon addition of a second equivalent of Zn^II, this coordinates to the sterically less accessible site B. From a similar titration with Ga^III, it emerges that only a mononuclear complex is obtained, with the Ga^III center coordinated to site A. When one equivalent of Ga^III is reacted with the mononuclear Zn^II complex, Zn^II is forced by Ga^III to exchange the site; this results in a dinuclear complex with Ga^III in site A and Zn^II in site B. With Cu^II, two isomers are observed: one with and the other without a bridging phenolate; these differ significantly in their spectroscopic and magnetic properties.     

Supramolecular hydrogen‐bonding patterns in the organic–inorganic hybrid compound bis(4‐amino‐5‐chloro‐2,6‐dimethylpyrimidinium) tetrathiocyanatozinc(II)–4‐amino‐5‐chloro‐2,6‐dimethylpyrimidine–water (1/2/2)

Zinc thiocyanate complexes have been found to be biologically active compounds. Zinc is also an essential element for the normal function of most organisms and is the main constituent in a number of metalloenzyme proteins. Pyrimidine and aminopyrimidine derivatives are biologically very important as they are components of nucleic acids. Thiocyanate ions can bridge metal ions by employing both their N and S atoms for coordination. They can play an important role in assembling different coordination structures and yield an interesting variety of one‐, two‐ and three‐dimensional polymeric metal–thiocyanate supramolecular frameworks. The structure of a new zinc thiocyanate–aminopyrimidine organic–inorganic compound, (C₆H₉ClN₃)₂[Zn(NCS)₄]·2C₆H₈ClN₃·2H₂O, is reported. The asymmetric unit consist of half a tetrathiocyanatozinc(II) dianion, an uncoordinated 4‐amino‐5‐chloro‐2,6‐dimethylpyrimidinium cation, a 4‐amino‐5‐chloro‐2,6‐dimethylpyrimidine molecule and a water molecule. The Zn^II atom adopts a distorted tetrahedral coordination geometry and is coordinated by four N atoms from the thiocyanate anions. The Zn^II atom is located on a special position (twofold axis of symmetry). The pyrimidinium cation and the pyrimidine molecule are not coordinated to the Zn^II atom, but are hydrogen bonded to the uncoordinated water molecules and the metal‐coordinated thiocyanate ligands. The pyrimidine molecules and pyrimidinium cations also form base‐pair‐like structures with an R₂²(8) ring motif via N—H…N hydrogen bonds. The crystal structure is further stabilized by intermolecular N—H…O, O—H…S, N—H…S and O—H…N hydrogen bonds, by intramolecular N—H…Cl and C—H…Cl hydrogen bonds, and also by π–π stacking interactions.     

Photoluminescence properties of a cationic trinuclear zinc(II) complex with the tetradentate Schiff base ligand 6‐methyl‐2‐({[(pyridin‐2‐yl)methyl]imino}methyl)phenolate

Metal complexes with Schiff base ligands have been suggested as potential phosphors in electroluminescent devices. In the title complex, tetrakis[6‐methyl‐2‐({[(pyridin‐2‐yl)methyl]imino}methyl)phenolato‐1:2κ⁸N,N′,O:O;3:2κ⁸N,N′,O:O]trizinc(II) hexafluoridophosphate methanol monosolvate, [Zn₃(C₁₄H₁₃N₂O)₄](PF₆)₂·CH₃OH, the Zn^II cations adopt both six‐ and four‐coordinate geometries involving the N and O atoms of tetradentate 6‐methyl‐2‐({[(pyridin‐2‐yl)methyl]imino}methyl)phenolate ligands. Two terminal Zn^II cations adopt distorted octahedral geometries and the central Zn^II cation adopts a distorted tetrahedral geometry. The O atoms of the phenolate ligands bridge three Zn^II cations, forming a dicationic trinuclear metal cluster. The title complex exhibits a strong emission at 469 nm with a quantum yield of 15.5%.     

Subcomponent Self‐Assembly of a 4 nm M4L6 Tetrahedron with ZnII Vertices and Perylene Bisimide Dye Edges

Formation of a tetrahedron with >4 nm perylene bisimide (PBI) dye edges and Zn^II vertices in a one‐pot 22 component self‐assembly reaction is reported. The luminescent polyhedron equilibrates to a Zn₂L₃ helicate and disassembles upon dilution. Insights into the subcomponent self‐assembly of extended PBI ligands help to refine design rules for constructing large photofunctional metallosupramolecular hosts.     

An Electron‐Deficient Porphyrin Tape

Hexakis(pentafluorophenyl)‐substituted meso–meso‐linked Zn^II–diporphyrin ( 9 ), which was prepared by the acid‐catalyzed cross‐condensation of 1,1,2,2‐tetrapyrroethane ( 5 ) with dipyrromethane dicarbinol ( 6 ), was converted into meso–meso,β‐β,β‐β triply linked Zn^II–diporphyrin 3 by oxidation with 2,3‐dichloro‐5,6‐dicyanobenzoquinone (DDQ) and Sc(OTf)₃. Beside the red‐shifted absorption spectrum and split first oxidation potential that are common to the triply‐linked Zn^II–diporphyrins, diporphyrin 3 exhibited considerably improved chemical stability owing to a lowered HOMO and good solubility in common organic solvents. The two‐photon absorption (TPA) cross‐section and S₁‐state lifetime of compound 3 were 1700 GM and 3.3 ps, respectively.     

Selective Catalytic Reduction of Nitric Oxide by Ammonia over Ag and Zn‐Exchanged Cuban Natural Zeolites

The catalytic selective reduction of NO over metal‐exchanged (Zn^II, Ag^I) natural zeolites (mordenite and clinoptilolite) from Cuba using NH₃ as a reducing agent in the presence of excess oxygen was studied. Both transition metals slightly improve the catalytic performance for the NO reduction. Zn^II‐exchanged zeolites exhibit a moderate catalytic activity, with conversions of NO of ≈58 % and high selectivity to N₂ at high temperatures.     

Carbonic Anhydrase‐Mimetic Bolaamphiphile Self‐Assembly for CO2 Hydration and Sequestration

A biomimetic catalyst was prepared through the self‐assembly of a bolaamphiphilic molecule with histidine moieties for the sequestration of carbon dioxide. The histidyl bolaamphiphilic molecule bis(N‐α‐amidohistidine)‐1,7‐heptane dicarboxylate has been synthesized and self‐assembled to produce analogues of the active sites of carbonic anhydrase (CA) after association with Zn²⁺ ions. Spectroscopic analysis demonstrated the coordination of the Zn²⁺ ions with histidine imidazole moieties, which is the core conformation of CA active sites. The Zn‐associated self‐assembly worked as a CA‐mimetic catalyst that shows catalytic activity for CO₂ hydration. Evaluation of the kinetics of using para‐nitrophenylacetate revealed that the kinetic parameters of the CA‐mimetic catalyst were maximized at the optimal Zn concentration and that excess Zn ions resulted in deteriorated catalytic activity. The performance of the CA‐mimetic catalyst was enhanced by changing the pH value and temperature of the reaction, which implies that the hydrolysis of the substrate is the rate‐determining step. The catalyst‐assisted sequestration of CO₂ was demonstrated by CaCO₃ precipitation upon the addition of Ca²⁺ ions. This study offers an easy way to prepare enzyme analogues for CO₂ sequestration through the self‐assembly of bolaamphiphile molecules with designer biochemical moieties.