Physcomitrella PpORS, basal to plant type III polyketide synthases in phylogenetic trees, is a very long chain 2'-oxoalkylresorcinol synthase.

The plant type III polyketide synthases (PKSs), which produce diverse secondary metabolites with different biological activities, have successfully co-evolved with land plants. To gain insight into the roles that ancestral type III PKSs played during the early evolution of land plants, we cloned and characterized PpORS from the moss Physcomitrella. PpORS has been proposed to closely resemble the most recent common ancestor of the plant type III PKSs. PpORS condenses a very long chain fatty acyl-CoA with four molecules of malonyl-CoA and catalyzes decarboxylative aldol cyclization to yield the pentaketide 2'-oxoalkylresorcinol. Therefore, PpORS is a 2'-oxoalkylresorcinol synthase. Structure modeling and sequence alignments identified a unique set of amino acid residues (Gln(218), Val(277), and Ala(286)) at the putative PpORS active site. Substitution of the Ala(286) to Phe apparently constricted the active site cavity, and the A286F mutant instead produced triketide alkylpyrones from fatty acyl-CoA substrates with shorter chain lengths. Phylogenetic analysis and comparison of the active sites of PpORS and alkylresorcinol synthases from sorghum and rice suggested that the gramineous enzymes evolved independently from PpORS to have similar functions but with distinct active site architecture. Microarray analysis revealed that PpORS is exclusively expressed in nonprotonemal moss cells. The in planta function of PpORS, therefore, is probably related to a nonprotonemal structure, such as the cuticle.

Supra-supra, supra-antara, and stepwise-diradical pathways for an observed 16-electron double-[4 + 4] cycloaddition within metal-templated dialkyne dimers (PtX2)2(µ-R2PCCCCPR2)2.

Quantum chemistry calculations are used to provide insight into the cycloaddition of two dialkyne chains in initially monocyclic organoplatinum dimers of the type (PtX(2))(2)(µ-R(2)PC(4)PR(2))(2), where X = Cl or Me and R = Ph or Me. Previous experimental studies showed that the cycloaddition occurs with {X, R} = {Cl, Ph} but not {Me, Ph}. Two concerted pericyclic paths, a D(2h)-symmetry double-[π4s+π4s] "Hückel path" and a D(2)-symmetry double-[π4s+π4a] "Möbius path", were explored via orbital energy correlation diagrams (OECDs) computed using a singly occupied molecular orbital technique developed earlier. In accord with pericyclic reaction theory, the 16e(-) rearrangement is forbidden along the D(2h) Hückel path; four electrons would need to change their orbital symmetries. The D(2) Möbius path, afforded by the natural twist in the reactant structure which allows the desired Möbius orbital connectivity for a 4n rearrangement, is concluded to be a borderline forbidden pathway. This Möbius path creates avoided crossings in the OECD, which allows consistent orbital populations throughout the reaction, but it does not cause a change in intended orbital correlation, and the predicted activation barrier is rather high (∼50 kcal mol(-1)). The avoided crossings show strong coupling, but a clear HOMO-LUMO gap for the reaction is not produced. A stepwise path is also presented, with evidence of its diradical character.

Sequential Electrophilic Substitution Reactions of Tungsten-Coordinated Phosphenium Ions and Phosphine Triflates.

ion of chloride from [W(CO)5{PPhCl2}] with AgOSO2CF3 leads to the phosphine triflate complex [W(CO)5{PPhCl(OSO2CF3)}] which undergoes electrophilic substitution reactions with N,N-diethylaniline, anisole, N,N-dimethyl-p-toluidine, toluene, biphenyl, naphthalene, 2,7,9,9-tetramethyl xanthene, and allyltrimethylsilane to form the chlorophosphine complexes [W(CO)5{PPhClR}], where R = p-diethylanilinyl, p-anisyl, 2-(N,N-dimethyl-4-methylphenyl), p-tolyl, p-phenylphenyl, 1-naphthyl, 4-(2,7,9,9-tetramethylxanthyl), and allyl. Abstraction of the second chloride with AgOSO2CF3 leads, in most cases, to the respective phosphine triflates [W(CO)5{PPhR(OSO2CF3)}], which react with ferrocene to form the ferrocenyl phosphine complexes [W(CO)5{PPhR(C10H9Fe)}]. The W(CO)5 unit can be removed via photolysis in the presence of bis(diphenylphosphino)ethane to form metal-free phosphines.

A potent synthetic inorganic antibiotic with activity against drug-resistant pathogens.

The acronymously named "ESKAPE" pathogens represent a group of bacteria that continue to pose a serious threat to human health, not only due to their propensity for repeated emergence, but also due to their ability to "eskape" antibiotic treatment. The evolution of multi-drug resistance in these pathogens alone has greatly outpaced the development of new therapeutics, necessitating an alternative strategy for antibiotic development that considers the evolutionary mechanisms driving antibiotic resistance. In this study, we synthesize a novel inorganic antibiotic, phosphopyricin, which has antibiotic activity against the Gram-positive methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus faecium (VRE). We show that this potent antibiotic is bactericidal, and exhibits low toxicity in an acute dose assay in mice. As a synthetic compound that does not occur naturally, phosphopyricin would be evolutionarily foreign to microbes, thereby slowing the evolution of resistance. In addition, it loses antibiotic activity upon exposure to light, meaning that the active antibiotic will not accumulate in the general environment where strong selective pressures imposed by antibiotic residuals are known to accelerate resistance. Phosphopyricin represents an innovation in antimicrobials, having a synthetic core, and a photosensitive chemical architecture that would reduce accumulation in the environment.

Sequential electrophilic P-C bond formation in metal-coordinated chlorophosphines.

In the presence of chloride abstractors, metal-coordinated chlorophosphines undergo facile room-temperature electrophilic substitution reactions with unsaturated organic substrates, leading to P-C bond formation. This methodology can be applied sequentially two or three times, stepwise or in one-pot reactions, to form phosphines with three different substituents. The reactions are rapid and high-yielding, and can be applied to a wide range of organic substrates, making them valuable tools for P-C bond formation.

Binuclear platinum-iridium complexes: synthesis, reactivity and luminescence.

The chemistry of the heterobinuclear platinum-iridium complex [PtIr(CO)3(µ-dppm)2][PF6], 1, dppm = Ph2PCH2PPh2, is described. The reaction of a hydride with 1 gave [HPtIr(CO)2(µ-dppm)2], by displacement of the carbonyl ligand from platinum, while reaction of 1 with dihydrogen, hydrogen chloride or Ph2MeSiH gave the fluxional complex [PtIrH4(CO)(µ-dppm)2][PF6], [PtIrH2Cl2(CO)(µ-dppm)2][PF6], or [PtIrH(SiMePh2)(CO)2(µ-dppm)2][PF6], respectively, by oxidative addition at iridium. Complex 1 reacted, often regioselectively, with several alkynes to give the µ-η(1),η(1) bridging alkyne complexes [PtIr(µ-RCCR')(CO)2(µ-dppm)2][PF6], R = H, R' = Ph, 4-C6H4Me, CO2Me; R = Ph, R' = CO2Me; R = R' = CO2Me. The complex [PtIr(µ-HCC-4-C6H4Me)(CO)2(µ-dppm)2][PF6] reacted reversibly with CO to give [PtIr(µ-HCC-4-C6H4Me)(CO)3(µ-dppm)2][PF6] and [PtIr(CO)3(µ-dppm)2][PF6], 1. With HCl, [PtIr(µ-HCC-4-C6H4Me)(CO)2(µ-dppm)2][PF6] reacted to give [PtIrHCl(µ-HCC-4-C6H4Me)(CO)2(µ-dppm)2][PF6], by oxidative addition at iridium, and then the alkenylplatinum derivative [PtIrCl{HC=CH(4-C6H4Me)}(CO)2(µ-dppm)2][PF6]. [PtIr(µ-HCC-4-C6H4Me)(CO)2(µ-dppm)2][PF6] reacted slowly with dihydrogen to give 4-MeC6H4CH=CH2 and [PtIrH4(CO)(µ-dppm)2][PF6]. The complex [PtIr(µ-HCCPh)(CO)2(µ-dppm)2][PF6] is intensely luminescent in solution at room temperature, with features characteristic of a d(8)-d(8) face-to-face complex.

Mixed nitrosyl/phosphinidene and nitrene/phosphinidene clusters of ruthenium.

Reaction of the aminophosphinidene complex [Ru5(CO)15(mu 4-PNPri2)] 1 with [PPN][NO2] (PPN = Ph3P=N=PPh3) led to the mixed nitrosyl/phosphinidene cluster complex [PPN][Ru5(CO)13(mu-NO)(mu 4-PNPri2)] 2 which is transformed into the novel nitrene/phosphinidene cluster [Ru5(CO)10(mu-CO)2(mu 3-CO)(mu 4-NH)(mu 3-PNPri2)] 3 via treatment with triflic acid.

Hypericum perforatum hydroxyalkylpyrone synthase involved in sporopollenin biosynthesis--phylogeny, site-directed mutagenesis, and expression in nonanther tissues.

Anther-specific chalcone synthase-like enzyme (ASCL), an ancient plant type III polyketide synthase, is involved in the biosynthesis of sporopollenin, the stable biopolymer found in the exine layer of the wall of a spore or pollen grain. The gene encoding polyketide synthase 1 from Hypericum perforatum (HpPKS1) was previously shown to be expressed mainly in young flower buds, but also in leaves and other tissues at lower levels. Angiosperm ASCLs, identified by sequence and phylogenetic analyses, are divided into two sister clades, the Ala-clade and the Val-clade, and HpPKS1 belongs to the Ala-clade. Recombinant HpPKS1 produced triketide and, to a lesser extent, tetraketide alkylpyrones from medium-chain (C6) to very long-chain (C24) fatty acyl-CoA substrates. Like other ASCLs, HpPKS1 also preferred hydroxyl fatty acyl-CoA esters over the analogous unsubstituted fatty acyl-CoA esters. To study the structural basis of the substrate preference, mutants of Ala200 and Ala215 at the putative active site and Arg202 and Asp211 at the modeled acyl-binding tunnel were constructed. The A200T/A215Q mutant accepted decanoyl-CoA, a poor substrate for the wild-type enzyme, possibly because of active site constriction by bulkier substitutions. The substrate preference of the A215V and A200T/A215Q mutants shifted toward nonhydroxylated, medium-chain to long-chain fatty acyl-CoA substrates. The R202L/D211V double mutant was selective for acyl-CoA with chain lengths of C16-C18, and showed a diminished preference for the hydroxylated acyl-CoA substrates. Transient upregulation by abscisic acid and downregulation by jasmonic acid and wounding suggested that HpPKS1, and possibly other Ala-clade ASCLs, may be involved in the biosynthesis of minor cell wall components in nonanther tissues.

Metal-templated diyne cyclodimerization and cyclotrimerization.

Reaction of [Pt(CH3)2(COD)] (COD = 1,5-cyclooctadiene) with Ph2PCCCCPPh2 led to a mixture of [{Pt(CH3)2}2(mu-Ph2PC4PPh2)2] (1) and [{Pt(CH3)2}3(mu-Ph2PC4PPh2)3] (2). Reaction of [PtCl2(COD)] with Ph2PCCCCPPh2 led to a mixture of the thermally unstable compounds [{PtCl2}2(mu-Ph2PC4PPh2)2] (3) and [{PtCl2}3(mu-Ph2PC4PPh2)3] (4) which transform into [{PtMe2}2{mu-C8(PPh2)4}] (5) and [{PtMe2}3{mu3-C12(PPh2)6}] (6) containing 8-membered diene-diyne and 12-membered triene-triyne rings, respectively. Compound 2 can be converted to [{PtMe2}3{C12(PPh2)6}] (7) by heating with CuCl at 80 degrees C, while 1 can be heated without significant cycloaddition.

Transformation of mu4-phosphinidenes at an Ru5 center: isolation and structural characterization of hydroxyphosphinidene cluster acids, fluorophosphinidenes, and a novel mu5-phosphide.

Acid hydrolysis of [Ru(5)(CO)(15)(mu(4)-PN(i)Pr(2))] (2) or protonation of the anionic PO cluster [Ru(5)(CO)(15)(mu(4)-PO)](-) (3) affords the hydroxyphosphinidene complex [Ru(5)(CO)(15)(mu(4)-POH)].1.[H(2)N(i)()Pr(2)][CF(3)SO(3)], which cocrystallizes with a hydrogen-bonded ammonium triflate salt. Reaction of [Ru(5)(CO)(15)(mu(4)-PN(i)Pr(2))] (2) with bis(diphenylphosphino)methane (dppm) leads to [Ru(5)(CO)(13)(mu-dppm)(mu(4)-PN(i)Pr(2))] (4). Acid hydrolysis of 4 leads to the dppm-substituted hydroxyphosphinidene [Ru(5)(CO)(13)(mu-dppm)(mu(4)-POH)] (5), which is analogous to 1, but unlike 1, can be readily isolated as the free hydroxyphosphinidene acid. Compound 5 can also be formed by reaction of 3 with dppm and acid. The cationic hydride cluster [Ru(5)(CO)(13)(mu-dppm)(mu(3)-H)(mu(4)-POH)][CF(3)SO(3)] (6) can be isolated from the same reaction if chromatography is not used. Compound 4 also reacts with HBF(4) to form the fluorophosphinidene cluster [Ru(5)(CO)(13)(mu-dppm)(mu(4)-PF)] (7), while reaction with HCl leads to the mu-chloro, mu(5)-phosphide cluster [Ru(5)(CO)(13)(mu-dppm)(mu-Cl)(mu(5)-P)] (8).

A thermally stable and sterically unprotected terminal electrophilic phosphinidene complex of cobalt and its conversion to an eta(1)-phosphirene.

The terminal chloroaminophosphido complex [Co(CO)3(PPh3){P(Cl)NiPr2}] is formed via reaction of K[Co(CO)4] with iPr2NPCl2 in the presence of triphenylphosphine. Chloride abstraction by aluminum trichloride leads to the first terminal phosphinidene complex of cobalt, [Co(CO)3(PPh3)(PNiPr2)][AlCl4]. The electrophilicity of the phosphinidene was demonstrated by its reaction with diphenylacetylene to form the phosphirene complex [Co(CO)3(PPh3){P(NiPr2)C(Ph)C(Ph)}][AlCl4].

Selective coupling of methylene groups at a Rh/Os core, yielding C2, C3, or C4 fragments: roles of the adjacent metals in carbon-carbon bond formation.

The mixed-metal complex, [RhOs(CO)(4)(dppm)(2)][BF(4)] (1; dppm = micro-Ph(2)PCH(2)PPh(2)) reacts with diazomethane to yield a number of products resulting from methylene incorporation into the bimetallic core. At -80 degrees C the reaction between 1 and CH(2)N(2) yields the methylene-bridged [RhOs(CO)(3)(micro-CH(2))(micro-CO)(dppm)(2)][BF(4)] (2), which reacts further at ambient temperature to give the allyl methyl species, [RhOs(eta(1)-C(3)H(5))(CH(3))(CO)(3)(dppm)(2)][BF(4)] (4). At intermediate temperatures compounds 1 and 2 react with diazomethane to yield the butanediyl complex [RhOs(C(4)H(8))(CO)(3)(dppm)(2)][BF(4)] (3) by the incorporation and coupling of four methylene units. Compound 2 is proposed to be an intermediate in the formation of 3 and 4 from 1 and on the basis of labeling studies a mechanism has been proposed in which sequential insertions of diazomethane-generated methylene fragments into the Rh-C bond of bridging hydrocarbyl fragments occur. Reaction of the tricarbonyl species, [RhOs(CO)(3)(micro-CH(2))(dppm)(2)][BF(4)] with diazomethane over a range of temperatures generates the ethylene complex [RhOs(eta(2)-C(2)H(4))(CO)(3)(dppm)(2)][BF(4)] (7a), but no further incorporation of methylene groups is observed. This observation suggests that carbonyl loss in the formation of the above allyl and butanediyl species only occurs after incorporation of the third methylene fragment. Attempts to generate C(2)-bridged species by the reaction of 1 with ethylene gave no reaction, however, in the presence of trimethylamine oxide the ethylene adducts [RhOs(eta(2)-C(2)H(4))(CO)(3)(dppm)(2)][BF(4)] (7b; an isomer of 7a) and [RhOs(eta(2)-C(2)H(4))(2)(CO)(2)(dppm)(2)][BF(4)] (8) were obtained. The relationship of the above products to the selective coupling of methylene groups, and the roles of the different metals are discussed.