Joseph C. Calabrese

C−H Insertion Reactions of Nucleophilic Carbenes

Syntheses and characterizations are described for C−H insertion products derived from 1,3-dimesityldihydroimidazol-2-ylidene (1) with acetylene, acetonitrile, methyl phenyl sulfone, and chloroform. In the reaction with acetylene, both acetylenic H-atoms are reactive so that 1u2009:u20091 and 2u2009:u20091 adducts can be obtained. The acetylene and methyl-phenyl-sulfone adducts are structurally characterized by means of single-crystal X-ray structure determinations. The reactions of 1,3,4,5-tetramethylimidazolidin-2-ylidene (8) with chloroform or chlorodifluoromethane are shown to yield 2-(dihaloalkyl)imidazolium salts that arise from a failure of the intermediate 2-protioimidazolium salt to capture the initially formed halocarbanion.

COINAGE METAL-CATALYZED HYDROBORATION OF IMINES

Abstract The preparation of several new coinage metal complexes containing bulky, chelating bis(phosphine) ligands is described. The molecular structures of [AuCl(μ-DiPPE)]n (4), [Cu(μ-Cl)(DHP)]2 (6a), and [Au(DHP)(PEt3)]Cl (8) have been determined (DiPPE = 1,2-bis(diisopropylphosphino)ethane, DHP = deerhead phosphine, o-phenylenebis(diisopropylphosphine). These new complexes are selective catalysts for the hydroboration of imines and thiazolinesus ing catecholborane. The molecular structure of (11) is also reported.

Crystal structure of riboflavin synthase

BACKGROUNDnRiboflavin synthase catalyzes the dismutation of two molecules of 6,7-dimethyl-8-(1-D-ribityl)-lumazine to yield riboflavin and 4-ribitylamino-5-amino-2,6-dihydroxypyrimidine. The homotrimer of 23 kDa subunits has no cofactor requirements for catalysis. The enzyme is nonexistent in humans and is an attractive target for antimicrobial agents of organisms whose pathogenicity depends on their ability to biosynthesize riboflavin.nnnRESULTSnThe first three-dimensional structure of the enzyme was determined at 2.0 A resolution using the multiwavelength anomalous diffraction (MAD) method on the Escherichia coli protein containing selenomethionine residues. The homotrimer consists of an asymmetric assembly of monomers, each of which comprises two similar beta barrels and a C-terminal alpha helix. The similar beta barrels within the monomer confirm a prediction of pseudo two-fold symmetry that is inferred from the sequence similarity between the two halves of the protein. The beta barrels closely resemble folds found in phthalate dioxygenase reductase and other flavoproteins.nnnCONCLUSIONSnThe three active sites of the trimer are proposed to lie between pairs of monomers in which residues conserved among species reside, including two Asp-His-Ser triads and dyads of Cys-Ser and His-Thr. The proposed active sites are located where FMN (an analog of riboflavin) is modeled from an overlay of the beta barrels of phthalate dioxygenase reductase and riboflavin synthase. In the trimer, one active site is formed, and the other two active sites are wide open and exposed to solvent. The nature of the trimer configuration suggests that only one active site can be formed and be catalytically competent at a time.

Crystal structure of 3,4-dihydroxy-2-butanone 4-phosphate synthase of riboflavin biosynthesis.

BACKGROUNDn3,4-Dihydroxy-2-butanone-4-phosphate synthase catalyzes a commitment step in the biosynthesis of riboflavin. On the enzyme, ribulose 5-phosphate is converted to 3,4-dihydroxy-2-butanone 4-phosphate and formate in steps involving enolization, ketonization, dehydration, skeleton rearrangement, and formate elimination. The enzyme is absent in humans and an attractive target for the discovery of antimicrobials for pathogens incapable of acquiring sufficient riboflavin from their hosts. The homodimer of 23 kDa subunits requires Mg(2+) for activity.nnnRESULTSnThe first three-dimensional structure of the enzyme was determined at 1.4 A resolution using the multiwavelength anomalous diffraction (MAD) method on Escherichia coli protein crystals containing gold. The protein consists of an alpha + beta fold having a complex linkage of beta strands. Intersubunit contacts are mediated by numerous hydrophobic interactions and three hydrogen bond networks.nnnCONCLUSIONSnA proposed active site was identified on the basis of amino acid residues that are conserved among the enzyme from 19 species. There are two well-separated active sites per dimer, each of which comprise residues from both subunits. In addition to three arginines and two threonines, which may be used for recognizing the phosphate group of the substrate, the active site consists of three glutamates, two aspartates, two histidines, and a cysteine which may provide the means for general acid and base catalysis and for coordinating the Mg(2+) cofactor within the active site.

Formation of a hydroxymethyliridium(III) compound and addition of the OH bond to bound acetonitrile

The hydridoformyliridium complex [IrH(CHO)(PMe3)4][PF6] (2) reacts with HBF4/diethyl ether in acetonitrile to form the hydroxymethyl complex [Ir(CH2OH)(CH3CN)(PMe3)4][PF6][BF4] (4). A hydrido hydroxycarbene complex 3 is believed to be an intermediate in this reaction. The acetonitrile ligand of compound 4 undergoes base-catalyzed attack by the oxygen atom of the hydroxymethyl group to form the metallacycle compound [Ir(CH2OC(CH3ue5fbNH)(PMe3)4][PF6][BF4] (5). Compound 5 cocrystallizes with [HPMe3][BF4] in the monoclinic space group P21/c, a 13.772(2), b 13.436(2), c 19.506(3) A, β 90.02(1)°, V 3609 A3, Z = 4. Precision of the X-ray structural results is limited by disorder of all the anionic groups. Refinement of 374 variables on 5312 reflections with Fobs2 > 2σ(Fobs2) has converged at R = 0.079, Rw = 0.091.

Synthesis, characterization and biodistribution of neutral and lipid-soluble 99mTc-PAT-HM and 99mTc-TMR for brain imaging.

Two new ligand systems for complexation with 99mTc were prepared. The two analogs of bisaminoethanethiol (BAT): N,N-bis(2-methyl-2-mercaptopropyl)-2,2-dimethylpropylenediamin e (PAT-HM) and N,N-bis[2-(2-ethyl-1-mercaptopropyl)] ethylenediamine (TMR), form neutral and lipid soluble complexes with 99mTc that readily penetrate the blood-brain barrier following i.v. injection into rats. Although the 99mTc chelates do not display the prolonged brain retention required for use in single photon emission computed tomographic imaging studies, the fact that each ligand forms a neutral and lipid-soluble complex of high chemical stability when coordinated with 99mTc warrants further investigation to increase the site- and organ-specificity of these agents.

Resolution of α-aminoboronic esters by diastereoselective crystallization with pinanediols. Confirmation by X-ray analysis

Abstract A resolution method for α-aminoboronic esters 4a,b using chiral pinanediol is described.

Coordination Chemistry of ADPO

Abstract The hypervalent phosphorus compound, 3,7-di-t-butyl-5-aza-2,8-dioxa-1-phosphabicyclo-[3.3.0]octa-2,4,6-triene (ADPO) forms adducts with chromium, tungsten, nickel and palladium metal centers. All four new adducts contain tetrahedral phosphorus atoms as a result of folding of the ADPO unit. This folding of the planar 10-P-3 ADPO molecule to provide an 8-P-3 center for coordination to the transition metal center is the result of the close energy balance between 10-P-3 ADPO and 8-P-3 ADPO and the strength of the phosphorus-metal interaction. In the case of a homoleptic palladium(II) complex, dimerizati on of the coordinated ADPO unit was observed.