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The biodistribution profiles in mice of two pyrrole-imidazole polyamides were determined by PET. Pyrrole-imidazole polyamides are a class of small molecules that can be programmed to bind a broad repertoire of DNA sequences, disrupt transcription factor-DNA interfaces, and modulate gene expression pathways in cell culture experiments. The [sup.18]F-radiolabeled polyamides were prepared by oxime ligation between 4-[[sup.18]F]-fluorobenzaldehyde and a hydroxylamine moiety at the polyamide C terminus. Small animal PET imaging of radiolabeled polyamides administered to mice revealed distinct differences in the biodistribution of a 5-ring [beta]-linked polyamide versus an 8-ring hairpin, which exhibited better overall bioavailability. In vivo imaging of pyrrole-imidazole polyamides by PET is a minimum first step toward the translation of polyamide-based gene regulation from cell culture to small animal studies. biodistribution | fluorine-18 | oxime | radiosynthesis

Research has been conducted on the mononuclear cis-dimethoxo octahedral Fe(III) complex with a singly deprotonated monoanionic ligand and the dinuclear mu-oxo trigonal bipyramidal Fe(III) complex with a doubly deprotonated dianionic ligand. The syntheses and characterization of these complexes are described.

Research has been conducted on the anion receptors. Results indicate that electrically neutral biimidazole diamides can serve as anion-sensitive fluorophores and as H-bond donors.

Research has been conducted on the deoxyribonucleoside of 4-fluoro-6-methylbenzimidazole. The preparation and structure of this compound have been investigated and discussed.

Research has been conducted on 4,4'-biimidazole synthesis. The preparation of these compounds via palladium-catalyzed coupling of 4-iodo-1-triphenylmethylimidazoles is described.

Research has been conducted on the ruthenium(II)- and ruthenium(III)-chloride-dimethyl sulfoxide precursors and the antimetasatic drug [ImH][trans-RuCl (sub)4 (dmso-S)] (Im= imidazole, dmso= dimethyl sulfoxide). The reactivity of these compounds toward nitric oxide has been studied and the details are reported.

Research has been conducted on the photochemical dyad. The assembly of this dyad which involves a zinc(II) and a free base porphyrins has been investigated and the results are reported.

Research has been conducted on the tetrahydro-1H-pyrrolo[1,2-a]imidazole-2-ones and hexahydroimidazo[1,2-a]pyridine-2(3H)-ones. The syntheses of these optically active compounds has been carried out and the details are reported.

Research has been conducted on the 5-guanidino-4-nitroimidazole lesion. The method developed for detection of this lesion in DNA is discussed.

Research has been conducted on the 1,4-disubstituted 2-imidazolines. The preparation of these enantiopure compounds has been carried out and the details are discussed.

Research has been conducted on the imidazoles' fluorinated analogues. The protocol for the beta-aryl-beta-fluoro-acrylic acid preparation has been developed and its use for the syntheses of (E)- and (Z)-beta-fluorourocanic acids is described.

Research has been conducted on the shape-modified nucleosides, 'fleximers' with the adenosine, inosine and guanosine purine ring system. The synthesis of these nucleosides carried out in investigating the nucleic acid structure, function and stability and the enzyme binding site parameters is discussed.

Research has been conducted on the inorganic or/and organic molecule assemblies. The use of polyoxovanadate as a structural building block in the hydrogen bonded inorganic-organic three-dimensional structure synthesis is described.

Research has been conducted on the thiocyanatonickel(II) and thiocyanatocobal(II) complexes of the Ni(NCS) (sub)2 (Hlm) (sub)2 and Co(NCS) (sub)2 (Hlm) (sub)2 where Hlm is imidazole. The preparation of these complexes has been carried out and the crystal structure of Ni(NCS) (sub)2 (Hlm) (sub)2 has been investigated via the use of X-ray methods.

Research has been conducted on symmetrical and unsymmetrical 2,2'-dipyridylamines. The reactions of these compounds with 1,2-dibromoethane and 1,3-dibromopropane producing imidazopyridinium and pyridopyrimidium bromides are described.

Research has been conducted on the F65A/Y131C murine alpha-carbonic anhydrase V. The crystal structure of this anhydrase has been investigated in examining the catalytic proton shuttle features and the results are reported.

Research has been conducted on the chiral xanthine CVT-124. The route for the scaleable synthesis of this compound has been developed via the late stage pyrimidine ring closure of the nitrogen-protected endo 2-norbornenyl imidazole and the results are presented.

Research has been conducted on the binary metal imidazolates of the group 10 metals. The preparation of these compounds has been carried out and the results indicate that these compounds are amorphous.

Research has been conducted on the Trypanosoma cruzi, the causative agent of Chagas disease. The efforts to develop anti T. cruzi agents have resulted in the study of the 1-[[(2-chlorophenyl)diphenyl]methyl]-1H-imidazole (CTZ) and cis-1-acetyl-4-[4-[[2-(2,4-dichlorophenyl)-2(1H-imidazol-1-ylmethyl)-1,3-dioxolan-4-yl]methoxy]phenyl]piperazine) (KTZ) coordination to gold and copper ions to produce and characterize new Cu(II)-CTZ and Cu(II)-KTZ, Au(I)-CTZ and Au(I)-KTZ complexes and the details are reported.

Research has been conducted on the structurally diverse peptidic and nonpeptidic compounds synthesized via the solid-phase approaches. The synthesis of the imidazolines and bis-imidazolines carried out via cyclization using resin-bound amino acids as the starting materials is reported.

Research has been conducted on the 2-alkoxycarbonylcycloimmonium N-aminides. The reaction of these compounds with such heterocumulenes as iso(thio)cyanates and carbodiimides has been investigated and the results indicate that this reaction produces heterobetaines containing imidazo[2,1-f][1,2,4]triazinium system.

Research has been conducted on the proton transfer pathway to Q (sub)B. The study of this pathway in the reaction center from Rhodobacter sphaeroides has been carried out and the results demonstrate that the binding of Zn (super)2+ or Cd (super)2+ to the reaction center surface at His-H126, His-H128 and Asp-H124 inhibits the proton transfer rate to Q (sub)B.

Research has been conducted on the cytochrome c oxidase. The synthesis of the imidazole-based tridentates which contain -OH or -NHCH (sub)3 intermediates for the cytochrome c oxidase model studies is described.

Research has been conducted on the bidentate ligands. The effects of these ligands on the mu-hydroxo Cu(II) complex activities have been investigated, and the preparation of the nitrogen-chelating bidentate ligand complexes and their application to the imidazole coupling with the arylboronic acids are described.

Research has been conducted on the functionalized vinylic derivatives of imidazo[1,2-alpha]pyridines. The use of the semiempirical AM1 and ab initio methods in investigating the heterocyclization of these derivatives is described.

Research has been conducted on the side-chain-fluorinated histamines. Results indicate that the addition of 'FBr' to 1-trityl-4-vinyl-1H-imidazole that occurs with the Markovnikov regioselectivity provides the route to these histamines.

Research has been conducted on polynucleating open-chain systems. Synthesis of the polynuclear acyclic systems that are the structural building-blocks for new molecular architectures and materials construction is discussed.

Research examines the functional and spectroscopic behavior of axial histidine-175 complexed with imidazole in a histidine-175 deletion mutant. Data show that imidazole coordination to histidine-175 produces several conformational forms of the enzyme including a wild type cytochrome c peroxidase.

Results demonstrate that bound imidazole in place of histidine-175 in cytochrome c imposes steric restrictions on the histidine. However, the substitution restrains the heme and its ligand from structural distortions.

Synechococcus PCC7942 SmtB has been found to bind one zinc ion per monomer with high affinity in a tetrahedral coordination geometry. Optical spectroscopic study was carried out and showed that SmtB binds 1 mol equiv of Co(II) in a tetrahedral or distorted tetrahedral environment with two or one cysteine thiolate ligands in the first coordination shell. The presence of a mixture of carboxylate and imidazole-containing ligands is likely.

Imidazole (imidH) was used as a ligand precursor to isolate the polymer (Fe3(imid)6(imidH)2)chi. X-ray crystallography revealed a structure with both tetrahedral and octahedral FE9(II) centers, linked by bridging imidazolate ligands. The resulting product was a pale yellow crystalline material of empirical composition FE3(imid)6(imidH)2, with two d-d absorption bands at 1265 and 1960mm.

The binding sites for L-arginine, dioxygen, and BF4 are near each other in recombinant human inducible nitric oxide synthase (rH-iNOS), a cytochrome P(sub 450) monooxygenase. Imidazole and 1-phenylimidazole are competitive suppressors of rH-iNOS, and bind to the sixth axial ligand of the heme. The enzymatic inhibition involves the deprotonation of an ionizable group. The binding of these compounds to rH-iNOS produces type II difference spectra. L-arginine binding displaces the imidazole from the enzyme.

An analysis of intact unanesthetized newts reveals that direct measurement of alpha-imidazole using NMR spectroscopy can also be used to determine the pK values of carnosine and imidazole fractions over temperatures varying from 4 to 40 degrees Celsius. Carnosine and imidazole exhibit similar Delta-pK/Delta-T. Alpha-imidazole does not significantly change in a carnosine containing closed solution.

Research has been conducted on the 4,5-dimagnesioimidazoles. The generation of these compounds has been carried out via the reaction of the vicinal dianions with various electrophiles and the details are reported.

Research has been conducted on the dioxouranium(VI) species. The precipitation of this complex from the room-temperature ionic liquid medium which contains 1-butyl-3-methylimidazolium nitrate, acetone and nitric acid has been investigated and the details are reported.

Research has been conducted on the C- and N-bound isomers. The relative stability of these isomers and the equilibrium position with the N-bound imidazole rearranging to the C-bound form have been investigated and the results are described.

We propose a concept for the rational design and synthesis of highly selective chemotherapeutic agents that makes direct use of genetic information about the disease state. The key idea is to use the mRNA or DNA specific to the disease state to trigger the catalytic release of a cytotoxic drug by promoting the association of a prodrug with a catalyst capable of releasing the drug. We demonstrate the feasibility of such an approach in vitro with a model system that is based on the hydrolysis of p-nitrophenyl esters by imidazole. In our model system, the catalytic component consists of an imidazole group linked to the 5' end of a 15-mer that is complementary to the 5' end of the triggering oligodeoxynucleotide. The corresponding prodrug component consists of a p-nitrophenol ester linked to the 3' end of an 8-mer oligodeoxynucleotide that is complementary to the 3' end of the triggering sequence. We show that this system efficiently releases p-nitrophenol in the presence of all three components and that the reaction is catalytic and undergoes multiple turnovers. We also show that the complex between the catalytic component and the triggering oligodeoxynucleotide behaves like an enzyme and follows Michaelis-Menten kinetics, with a [K.sub.M] of 22 [micro]M and a [k.sub.cat] of 0.018 [min.sup.-1]. Most importantly, we show that catalytic release of p-nitrophenol is sensitive to the presence of a single base-pair mismatch.

Research has been conducted on the imidazolium ionic liquids. The use of these liquids at room temperature for iridium nanoparticles' formation and stabilization is described.

Research has been conducted on the coordination polymers formed in aqueous solution with copper(II), trimesic acid, and imidazole at room temperature. Results indicate that the stability of these polymers depend on the hydrogen bonding.

A nomenclature system has been assigned to facilitate the functional and biochemical study of imidazoline receptor sites. Clonidine analogs that exhibit nanomolar binding properties are classified as I1 sites while those that show micromolar binding properties and are labelled by (3H)idazoxan are classified as I2 sites. Moreover, developments in purification, selective antisera and photoaffinity probes may result in better identification of I2 sites. In addition, researches on the actions of rilmenidine and moxonidine drugs may benefit the study of the physiological functions of imidazoline receptors.