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Fluorescently labeled models of the prion protein that allow prion-prion (PrP-PrP) interactions and metal binding ([Cu.sup.2+] and [Zn.sup.2+]) to be investigated on the molecular level were developed. The results show that PrP-PrP interactions are promoted by addition of [Cu.sup.2+] and [Zn.sup.2+] and glutamine and tryptophan residues also play an important role in PrP-PrP interactions.

Asymmetric hetero-Diels-Alder (HDA) reactions of N-sulfinyl dienophiles are described using bis(oxazoline)-copper(II) and -zinc(II) triflates and the cycloadditions with cyclic and acyclic 1,3-dienes are studied. The HDA adducts are transformed into N-protected alpha-amino acid methyl esters, amino esters, amino alcohols, and homoallylic amines.

A nickel-catalyzed synthesis of unsymmetrical aryl sulfides from various aryl iodides and dialkyl- or diaryl-disulfide by the addition of zinc in one-pot is described. Two RS groups in (RS)2 can be used in this system.

A mild Negishi cross-coupling of 2-heterocyclic organozinc reagents and aryl chlorides in presence of [Pd.sub.2][(dba).sub.3] and X-Phos as a ligand to obtain high yields of product is described. An efficient method to generate the organozinc reagents at room temperature is also demonstrated.

The significance of zinc in the assembly of the sterile alpha motif (SAM) domain of diacylglycerol kinase [delta] is analyzed. Zinc is found to be extremely significant for the assembly, as well as the physiology of the compound.

Density functional theory (DFT) is used for examining the zinc carbenoid-mediated homologation reaction of [beta]-keto esters. Pathway B has explained the proposed, but spectroscopically unobservable donor-acceptor cyclopropane intermediate, while the second pathway A has disclosed an alternative to the classical intermediate in that a cyclopropane transition state leads to product.

Electrospray-ionization mass spectrometry was used to detect the charge-tagged organometallics due to reaction of the organic iodides bearing a cationic quaternary ammonium group at a remote position with zerovalent Pd complexes, Zn, or In leading to a C-I bond insertion. The proposed method allows a straightforward identification of the rate-limiting step and the determination of the corresponding second-order rate constant.

The phospha-Michael reaction to effectively synthesize a new catalyst on the basis of Trost s dinuclear catalyst without using pyridine is discussed. The unprecedented asymmetric additions of dialkylphosphine oxides to N-sulfinylimines which is achieved by using [Et.sub.2]Zn as a base is also discussed.

A high-resolution structure of enzyme Co(II)-BcII from Bacillus cereus which revealed a metal coordination geometry identical to that of the native zinc enzyme dependent [beta]-lactamase is presented. A considerable flexibility observed in the two loops of Cys ligand containing four metal ligands could assist in the in the structural rearrangement of the metal sites during catalytic turnover, which, along with the coordination geometry adaptability of Zn(II) ions, grants the interaction with a variety of substrates, a characteristic feature of B1 metallo-[beta[-lactamases.

The crystal structure of CyanoP (Tlr2075) from Thermosynechococcus elongates at 2.8 [Angstrom] is described. The studies have shown that CyanoP has adopted the same [beta]-sandwich fold as higher-plant PsbP and contains a well-conserved metal (zinc)-binding site that is present in plant PsbP.

The reversal of enantioselectivity in a Cu-catalyzed asymmetric conjugate addition reaction of dialkylzinc to cyclic enone with use of the same chiral ligand is achieved. The treatment of 2-cyclohepten-1-one with [Et.sub.2]Zn catalyzed by Cu[(OTf).sub.2] combined with a benzimidazolium salt has produced the corresponding (S)-conjugate adduct in a 92:8 enantiomer ratio (er), while the Cu[(acac).sub.2]-catalyzed reaction with the same ligand has produced (R)-product in 9:91 er.

The structures of the pathogenic human copper-zinc superoxide dismutase (SOD1) variants D124V and H80R, both of which demonstrate compromised zinc-binding sites are presented. The findings provide support to the view that immature mutant SOD1 species contribute to toxicity in SOD1-linked inherited form of the fatal neurodegenerative disease amyotrophic lateral sclerosis (ALS).

A new approach is described for preparing diorganyl selenides. Zinc dust is used in BMIM-B[F.sub.4] to prepare a series of diorganyl selenides under neutral reaction conditions.

Variable amino acids were reacted with tetraamino zinc phthalocyanine to synthesize a new family of G-quadruplex ligands termed 'amido phthalocyanines' (APcs). The results offer insight into the mechanism for the 'turn on' fluorescence properties exhibited by the synthesized compounds that could be used for future design of new G-quadruplex-specific fluorescent probes and drug candidates.

A new 1,3-diderivative of calix[4]arene appended with hydroxymethyl salicylyl imine is prepared and its ion recognition toward biologically relevant [M.sup.n+] ions is analyzed. The studies have shown that while [H.sub.2]L is selective for [Zn.sup.2+] among a number of cations, the [ZnL] is selective toward phosphate among a number of anions and also toward Asp, Cys and His among the naturally occurring amino acids.

The mechanisms of peroxynitrite (ONO[O.sup.-])-induced endothelial nitric oxide synthase (eNOS) dysfunction and their dose dependence are examined to study the controversial inactivation of eNOS by peroxynitrite due to oxidation of the eNOS zinc thiolate cluster rather than the cofactor tetrahydrobiopterin (B[H.sub.4]). The loss of Zn binding induced by peroxynitrite treatment which does not account for loss of enzyme activity suggested that ONO[O.sup.-]-induced eNOS inactivation is primarily due to oxidation of B[H.sub.4] and irreversible destruction of the heme/heme center.

The crystal structure characterization of cyanobacterial PsbQ isolated from Synechocystis sp. in presence and absence of [Zn.sup.2+] is described. The characterization identified the protein as a well-defined helical core, containing four helices arranged in an up-down-up-down fold and a conserved potential interaction site composed of a divalent metal binding site and adjacent hydrophobic pocket.

Thiomethyl-substituted N-heterocycles like pyridines, isoquinolines, pyrimidines, pyrazines, quinazolines, triazines, benzothiazoles or benzoxazoles have undergone Ni-catalyzed cross-coupling reactions with functionalized aryl-, heteroaryl-, alkyl- and benzylic zinc reagents by using Ni[(acac).sub.2]/DPE-Phos catalytic system.

The covalent modification observed in human copper-zinc superoxide dismutase (SOD1) was characterized to ascertain it as a novel heptasulfane bridge connecting the two Cys111 residues in the SOD1 homodimer. The modification might provide SOD1 with a toxic gain of function due to the catalytic ability of polysulfanes and polysulfides to catalyze the generation of reaction oxygen and sulfur species.

A large human carbonic anhydrase II (HCA II) crystal at pH 9.0 is prepared and subjected to vapor H-D exchange to replace labile hydrogen with deuterium to understand structural details of HCA II active site and proton transfer pathway. The interesting active site features of the structure and a proposed mechanism for proton transfer is also discussed based on the findings for Zn-bound solvent molecule in the active site.

The crystal structure characterization of human carbonic anhydrase II (HCA II) is obtained at 0.9 [Angstrom] resolution to reveal a water molecule, termed deep water, Dw, bound in a hydrophobic pocket of the active site that forms a short, strong hydrogen bond with the zinc-bound solvent molecule. The short, strong hydrogen bond formed is expected to contribute to the low p[K.sub.a] of the zinc-bound water and to promote proton transfer in catalysis.

A study was conducted to understand the rapid and reversible decrease in the water permeability of a predominant water channel in the brain, aquaporin-4 (AQP4), when it is reconstituted into proteoliposomes mediated by [Zn.sup.2+]. The obtained results indicated that the water permeability of AQP4 might be regulated by dynamic changes in intracellular [Zn.sup.2+] concentration related to the cellular redox state.

Ligand competition with a number of chromophoric probes were used to determine the binding affinities for [Zn.sup.II] and [Cu.sup.I] of each metal-binding domain (MBD). The obtained information highlighted the potential toxicity of [Cu.sup.+] in vivo and more sensitive magnitude of copper sensor proteins compared to zinc sensor proteins.

The identification of a cyclic phosphodiesterase which have ability to hydrolyze the 7,8-Dihydro-D-neopterin 2',3'-cyclic phosphate ([H.sub.2]N-cP) and convert it to a mixture of 7,8-dihydro-D-neopterin 2'-monophosphate and 7,8-dihydro-D-neopterin 3'-monophosphate is reported. The direct metal analysis of the recombinant enzyme from Methanocaldococcus jannachii designated as MptB demonstrated that MptB contained 1.0 mol of zinc and 0.8 mol of iron per protomer and required [Fe.sup.2+] for activity similar to one observed for MptA.

The rate constants of the hydride-transfer reactions from isopropyl alcohol (i-PrOH) to an [NAD.sup.+] model, 9-phenylxanthylium (Ph[Xn.sup.+]), in acetonitrile (AN) and in water containing AN are determined over a wide temperature range. The results have shown that in the alcohol dehydrogenases without a Zn(II) cofactor in the active sites alcohols is oxidized by hydride transfer to [NAD.sup.+] coenzyme followed by the rapid deprotonation to the nearby basic species in the active site of the enzymes.

Al[Cl.sub.3] is used as Lewis acid for functionalized aldehydes to react with organozinc reagents to produce (E)-alkenes stereoselectively in high yields.

The important role of zinc towards the structural stability of human carbonic anhydrase II (HCA II) which is a monomeric zinc-containing metalloenzyme that catalyzes the hydration of C[O.sub.2] to form bicarbonate and a proton is reported. The results suggested that removal of zinc from the active site have no effect on either the topological fold of the enzyme or the ordered water network in the active site but altered the collective electrostatics of the apo-HCA II.

The characterization of human glyoxalase II (Glx2) overexpressed in rich medium and in minimal medium containing zinc, iron, or cobalt, and the resulting Glx2 analogues is carried out to determine the nature of the metal center in the Glx2 enzyme. The results suggested that Glx2 contains a Fe(II)Zn(II) center in vivo but their catalytic activity is attributed to Zn(II) in the Zn1 site.

The preparation and the analysis of a diketopiperazine based anion receptor bearing two dipicolylamino arms complexed to zinc(II) is described. Fluorescent indicator displacement assay has shown that the receptor binds di- and triphosphate ions with high affinity and selectivity in aqueous solution after adding zinc(II).

Several studies are conducted to explain the substrate binding and stereoselectivity phenomena observed in the Giardia lamblia fructose-1,6-bisphosphate aldolase (FBPA), a member of the II zinc-dependent aldolase family. The polarization of the substrate for protein transfer in the FBPA compound is shown to be highly dependent on the zinc mobility within it.

The diversity of the Sod1 gene in six arbuscular mycorrhizal fungi (AMF) species as well as 14 Glomus intraradices isolates from a single natural population is analyzed to gain insight into their ability to tolerate the oxidative stress from the surrounding environment. The results from analysis suggested that the persistent molecular diversity observed within the AMF population is attributed to diversified selection instead of recombination.

(-)-Spicigerolide is stereoselectively prepared from a protected (S)-lactaldehyde. The preparation of the polyacetylated framework has depended on two Zn-mediated stereoselective additions of alkynes to aldehydes as well as a regiocontrolled [3,3]-sigmatropic rearrangement of an allylic acetate.

Several studies are conducted to determine the applicability of low-affinity zinc coordination motifs in mediating the destabilization of the close-dependent rhodopsin. The process is shown to be extremely useful for the prevention of various diseases, like retinitis pigmentosa (RP) and the Alzheimer disease.

A combination of X-ray absorption spectroscopy and biochemical analysis approaches is employed to study the zinc-binding domain (ZBD), which helps in DNA recognition in the DNA replication system of bacteriophage T7. The zinc is shown to behave as the charge modulation indicator for the sulfur atoms, hence enabling an effective DNA recognition.

The affinity of phosphorylated forms of the tumor suppressor p53 N-terminal acidic transactivation domains (TAD) for the transcriptional adaptor zinc-binding (Taz2) domain of p300 is explored to understand the role of phosphorylation in the regulation of p53 interactions. The findings for the two binding sites on p53 for Taz2 provide evidence for the significant role of p53 posttranslational modifications in the regulation of its protein-protein interactions.

The application of a zinc carbenoid-mediated chain-extension reaction for the generation of a ketomethylene-based peptide-mimic of the human cytomegalovirus (HCMV) protease cleavage site is reported. The findings for the tandem chain-extension reactions could also be applied to amino acid systems to provide stereocontrolled access to a wide variety of peptide isosteres.

An alkylation of aminals with organozinc reagents derived from allyl bromide, benzyl amide, [alpha]-bromoacetate and [alpha]-bromonitrile is carried out in the presence of TMSCl and diisopropylamine. This reaction system is applied to the preparation of an antispasmodic, butaverine.

The rates of [beta]-elimination and protonation of [beta]-amino alkylzinc iodides are determined. The results have shown that the TFA group can be used for the protection of nitrogen in [beta]-amino alkylzinc iodides, since the precursor iodides are stable with respect to oxazoline formation, without adversely affecting the stability or reactivity of the alkylzinc iodide.

Several site-specific mutants of the zinc human carbonic anhydrase II (HCA II) with replacements at position 62 are compared and the efficiency of the catalysis in the hydration of C[O.sub.2] for the resulting mutants is characterized by [super.18]O exchange. The results have highlighted the roles of the residues of the hydrophilic side of the active site cavity in maintaining efficient catalysis by carbonic anhydrase.

Various synthetic routes are utilized to synthesize the tetrafunctionalized A[B.sub.3]-type porphyrin building blocks containing two different types of functional groups with [N.sub.4], [N.sub.3]O, [N.sub.3]S, and [N.sub.2][S.sub.2] porphyrin cores. The results from the studies on porphyrin tetrads and porphyrin pentads revealed that the monomeric porphyrin subunits in tetrads and pentads retained their individual characteristics features and exhibited weak interaction among the porphyrin subunits.

The synthesis and characterization of photochemically stable fluorescent heteroditopic ligands for zinc ion is reported. The zinc compounds are found to have better photochemical stability as well as higher degree of fluorescence turn-on upon formation of monozinc complexes when compared to their vinyl counterparts.

The carbonic anhydrase models that allows the specific recognition, activation and transfer of C[O.sub.2] as well as heteroallenes X=C=Y such as the polar or polarizable examples COS, C[S.sub.2], [H.sub.2]CCO, and RNCS are used to understand the general mode of biomimetic activation of a wide variety of cumulenes. The results obtained demonstrate the ability of allene to interact with models of carbonic anhydrase to allow the inexpensive transformation of cumulene.

The preparation and evaluation of a novel calix[4]arene-based fluorescent chemosensor is described for detecting [Cd.sup.2+] and [Zn.sup.2+]. The changes observed for the fluorescent spectra upon addition of various metal ions show that chemosensor is highly selective for [Cd.sup.2+] and [Zn.sup.2+] over other metal ions.

The naturally existing chlorophyll-a was used to prepare zinc 3-hydroxymethyl-protopyropheophorbide-d derivatives having carbonyl group(s) at the 13/15-, 13-, and 15-positions and lacking C=O group. The results revealed that both the presence of the C=O group and its situation at the 13-position were preferable for formation of the well-ordered J-aggregates.

The article discusses a new approach, where in several zinc-catalyzed cycloisomerization reactions are conducted for the synthesis of different furans and furopyrimidine nucleosides. The methodology is shown to be extremely effective and advantageous, as it is inexpensive with small reaction time.

The structure-function studies of the dizinc aminopeptidase from Vibrio proteolyticus were carried out to understand the correlation between charge/dipole polarity and ligand binding affinity. The results suggested that the coordination number and polarity might play significant role to tune the electrophilicity of zinc and the ability of the enzyme to discriminate between reaction coordinate species.