Palladium complexes with Pd-->B dative bonds: analysis of the bonding in the palladaboratrane compound [kappa4-B(mimBut)3]Pd(PMe3)

The dinuclear complex {[mu-kappa(1),kappa(3)-B(mim(Bu(t)))(3)]Pd}(2), which features a Pd-->B dative bond, may be obtained by the reaction of [Tm(Bu(t))]K with Pd(OAc)(2); treatment of {[mu-kappa(1),kappa(3)-B(mim(Bu(t)))(3)]Pd}(2) with PMe(3) affords the mononuclear boratrane derivative [kappa(4)-B(mim(Bu(t)))(3)]Pd(PMe(3)), for which a molecular orbital analysis indicates that the palladium center possesses a d(8) configuration.     

Where organometallics and dendrimers merge: the incorporation of organometallic species into dendritic molecules

This review will describe the ongoing efforts being made to incorporate organometallic fragments into the framework of dendrimers. While purely dendritic organic molecules are well known and well studied, species incorporating organometallic moieties potentially offer many benefits that are not available to only organic containing dendrimers. For example, catalytic or redox active organometallic functions can be included in the dendritic framework and impart these characteristics onto the dendrimer. This report will give an overview of the latest developments in this field by highlighting selected examples that detail novel synthetic strategies or dendrimer construction methodologies, interesting practical applications or address specific problems associated with organometallic dendrimers.     

Enantioselective Artificial Metalloenzymes Based on a Bovine Pancreatic Polypeptide Scaffold

Site creation : Enantioselective artificial metalloenzymes have been created by grafting a new active site onto bovine pancreatic polypeptide through the introduction of an amino acid capable of coordinating a copper(II) ion. This hybrid catalyst gave good enantioselectivities in the Diels–Alder and Michael addition reactions in water (see scheme) and displayed a very high substrate selectivity.

     

A small molecule discrimination map of the antibiotic resistance kinome

Kinase-mediated resistance to antibiotics is a significant clinical challenge. These enzymes share a common protein fold characteristic of Ser/Thr/Tyr protein kinases. We screened 14 antibiotic resistance kinases against 80 chemically diverse protein kinase inhibitors to map resistance kinase chemical space. The screens identified molecules with both broad and narrow inhibition profiles, proving that protein kinase inhibitors offer privileged chemical matter with the potential to block antibiotic resistance. One example is the flavonol quercetin, which inhibited a number of resistance kinases in vitro and in vivo. This activity was rationalized by determination of the crystal structure of the aminoglycoside kinase APH(2″)-IVa in complex with quercetin and its antibiotic substrate kanamycin. Our data demonstrate that protein kinase inhibitors offer chemical scaffolds that can block antibiotic resistance, providing leads for co-drug design.     

Group ib organometallic chemistry : XXXIV. Thermal behaviour and chemical reactivity of tetranuclear Me2N-substituted diarypropenylcopper-copper anion (Vi2Cu4X2) and mixed diarylpropenyl/organocopper (Vi2Cu4R2) compounds

Thermal decomposition of configurationally pure 1,2-diarylpropenylcopper compounds Z-Vi₂CU₄Br₂ and Z-Vi₂Cu₄R₂ [Vi  (2-Me₂NC₆H₄)CC(Me)-(C₆H₄Me-4), R  2-Me₂NC₆H₄ or 4-MeC₆H₄CC] predominantly results in the formation of ViH. In contrast, only dimers (ViVi) were formed on thermolysis of (Z-ViCu₂OTf)_η which is a further illustration of the influence of the counter anion on the reactivity of organocopper cluster compounds. However, in both cases partial inversion of configuration, giving mixtures of isomers, was observed. The thermolysis of (Z-ViCu₂OTf)_η is discussed in terms of OTf-enhanced intraaggregate electron-transfer processes. The formation of incipient vinyl cations which are η²-coordinated to the copper cluster can explain the observed isomerization.Also in the hydrolysis reaction of Z-Vi₂Cu₄Br₂ mixtures of isomeric ViH compounds were obtained, the E/Z ratio being dependent on the type of reagent used. Mixtures of isomeric ViX compounds (X  Br, Cl, I) were formed in the reaction of Z-Vi₂Cu₄Br₂ with I₂ and CuCl₂. An explanation for the occurrence of isomerization is presented.Dimers (ViVi) were almost absent in the product mixture resulting from the reaction of Z-Vi₂Cu₄Br₂ with CuCl₂. In contrast, ViVi is obtained in about 50% yield from the reaction of ViLi with CuCl₂ which is in accord with earlier observations for the reaction of aryllithium compounds with cupric halides.Highly selective E-ViBr formation was observed in the reaction of E-ViLi with AgBr. This reaction probably proceeds via a thermally unstable Z-ViAg₂Br intermediate.     

Stabilisation of [Fe2(CO)9] and [Ru2(CO)9] bu substitution with bridging diphosphorus ligands

Reaction of [Fe₂(CO)₉] with a half molar amount of R₂PYPR₂ (Y = CH₂, R = Ph, Me, OMe or OPrⁱ; Y = N(Et), R = OPh, OMe or OCH₂; Y = N(Me), R = OPrⁱ or OEt) leads to the ready formation of a product which on irradiation with ultraviolet light rapidly decarbonylates to the heptacarbonyl derivative [Fe₂(μ-CO)(CO)₆{μ-R₂PYPR₂}]. Treatment of the latter with a slight excess of the appropriate ligand results, under photochemical conditions, in the formation of the dinuclear pentacarbonyl complex [Fe₂(μ-CO)(C))₄{μ-R₂PYPR₂}₂] but under thermal conditions in the formation of the mononuclear species [Fe(CO)₃{R₂PYPR₂}]. Reaction of [Ru₃(CO)₁₂] with an equimolar amount of (RO)₂PN(R′)P(OR)₂ (R′ = Me, R = Prⁱ or Et; R′ = Et, R = Ph or Me) under either thermal or photochemical conditions produces [Ru₃(CO)₁₀{μ-(RO)₂PN(OR)₂}] which reacts further with excess (RO)₂PN(R′)P(OR)₂ on irradiation with ultraviolet light to afford the dinuclear compound [Ru₂(μ-CO)(CO₄{μ-(RO)₂PN(R′)P(OR)₂}₂]. The molecular structure of [Ru₂(μ-CO)(CO)₄{μ-(MeO)₂PN(Et)P(OMe)₂}₂], which has been determined by X-ray crystallography, is described.     

Synthesis of 3- and 4-(β-D-ribofuranosyl)-s-triazolo[2,3-a] pyrimid-7-one,isomers of inosine containing a bridgehead nitrogen atom

The first synthesis of a purine nucleoside analog containing a bridgehead nitrogen atom is here reported. The direct glycosylation of the trimethylsilyl derivative of s-triazolo[2,3-a] pyrimid-7-one has been shown to give 3-(β-D-ribofuranosyl)-s-triazolo[2,3-a]pyrimid-7-one (V) and 4-(β-D-ribof'uranosyl)-s-lriazolo[2,3-α]pyrimid-7-one (VII). The nueleoside V may he considered a close analog of inosine in which the nitrogen N₁ and C₅ of inosine have been interchanged. Bro-minalion of the tri-O-acelyl derivative IV gave, after deblocking, 6-bromo-3-(β-D-ribofurnaosyl)-s-triazolo[2,3-a] pyrimid-7-one (IX). Structural assignments of the nucleosides were made on the basis of comparison of the ultraviolet absorption spectral characteristics with 3-methyl-s-triazolo-[2,3-a]pyrimid-7-one (XI) and 4-methyl-s-lriazolo[2,3-a Jpyrimid-7-one (XII) prepared by a standard procedure from 7-methoxy-s-triazolo(2,3-a] pyrimidine (X).     

Biochemical evaluation of sulfur and nitrogen assimilation potential of mustard (Brassica juncea L. Czern. & Coss.) under application of slow-release sulfur fertilizer

Pot experiments were conducted to study the efficacy of a slow sulfur-releasing fertilizer, sulfur glass fritz (SGF 1), on growth, photosynthesis, and sulfur, and nitrogen assimilation potentials of brown mustard (Brassica juncea L. Czern. & Coss. cv. Pusa Jaikisan). Growth as indicated by biomass accumulation slowed down in response to the application of sulfur glass fritz. A similar trend was observed in the case of photosynthesis rate. The activity of two marker enzymes, ATP-sulfurylase and nitrate reductase, showed very low levels of activity, indicating poor assimilation of sulfur and nitrogen by the plant under sulfur glass fritz. It is therefore concluded that the release of sulfur by sulfur glass fritz is too slow and that the initial nonavailability of sulfur to the plants could lead to suboptimization of both sulfur- and nitrogen-assimilating enzymes. These factors may contribute to low rates of photosynthesis and poor growth.     

Electrostatics of cell membrane recognition: structure and activity of neutral and cationic rigid push-pull rods in isoelectric, anionic, and polarized lipid bilayer membranes.

Design, synthesis, and structural and functional studies of rigid-rod ionophores of different axial electrostatic asymmetry are reported. The employed design strategy emphasized presence of (a) a rigid scaffold to minimize the conformational complexity, (b) a unimolecular ion-conducting pathway to minimize the suprastructural complexity and monitor the function, (c) an extended fluorophore to monitor structure, (d) variable axial rod dipole, and (e) variable terminal charges to create axial asymmetry. Studies in isoelectric, anionic, and polarized bilayer membranes confirmed a general increase in activity of uncharged rigid push-pull rods in polarized bilayers. The similarly increased activity of cationic rigid push-pull rods with an electrostatic asymmetry comparable to that of alpha-helical bee toxin melittin (positive charge near negative axial dipole terminus) is shown by fluorescence-depth quenching experiments to originate from the stabilization of transmembrane rod orientation by the membrane potential. The reduced activity of rigid push-pull rods having an electrostatic asymmetry comparable to that in alpha-helical natural antibiotics (a positive charge near the positive axial dipole terminus) is shown by structural studies to originate from rod "ejection" by membrane potentials comparable to that found in mammalian plasma membranes. This structural evidence for cell membrane recognition by asymmetric rods is unprecedented and of possible practical importance with regard to antibiotic resistance.