A novel, tunable manganese coordination system based on a flexible "spacer" unit: noncovalent templation effects.

The reaction of bis(hexafluoroacetylacetonato)manganese(II) trihydrate (2), an approximately 90 degrees corner unit, with flexible linking unit 4,4'-trimethylenedipyridine (1) allows for the potential formation of three different types of solid-state coordination species: infinite helical polymers, closed dimeric systems, and infinite one-dimensional polymers. While the un-templated starting material is known to give a coordination helix, the other two possible species can be realized through the selective use of a variety of simple, organic guests: toluene (3), diphenylmethane (4), cis-stilbene (5), 1,3-diphenylpropane (6), benzyl alcohol (7), nitrobenzene (8), and cyanobenzene (9). When solutions of 1 and 2 are crystallized in the presence of all of these clathrates, the dimeric macrocycles result in all cases, except for that of 6, in which a syndiotactic, wedge-shaped polymer forms. Employing a linker that is less rigid than is typically used in crystal engineering, such as 1, enables the nucleophilic donor subunit to be more than just a simple "spacer", instead making it an essential, tunable component in the overall crystal lattice. In so doing, a great deal of molecular "information" is lost, but this is compensated for by an in-depth investigation into the weaker host-guest and/or guest-guest interactions, such as nonclassical hydrogen bonding and an assortment of hydrophobic interactions, present in the various systems.

Metal-directed formation of three-dimensional M(3)L(2) trigonal-bipyramidal cages.

[reaction: see text] The simple combination of two angular tritopic pyridine donor linkers (109 degrees bond angle) with three ditopic platinum acceptors (90 degrees bond angle) leads to essentially quantitative formation of self-assembled M(3)L(2) trigonal-bipyramidal (TBP) supramolecular species.

Self-assembly with postmodification: kinetically stabilized metalla-supramolecular rectangles.

Interaction of a predesigned molecular "clip" (4) with rigid dipyridyl bridging ligands, in acetone/water mixtures, leads to the formation of molecular rectangles (5-8) in 92-97% isolated yields via spontaneous self-assembly. Characterization was accomplished with multinuclear NMR and UV-vis spectroscopy, FAB mass spectrometry, and X-ray crystallography. The length of these metallamacrocycles ranges from 2 to 3 nm. Postmodification via non-nucleophilic counterion exchange results in enhanced structural integrity for the assemblies.

Palladium-catalyzed arylation of enynes and electron-deficient alkynes using diaryliodonium salts.

A new single-pot procedure for the synthesis of aryl alkynes is described. Palladium catalyzes the coupling reaction of diaryliodonium compounds with enynes and electron-deficient alkynes to give aryl alkynes in good yields.

Coordination-driven assembly of molecular rectangles via an organometallic "clip".

The combination of linear dipyridyl ligands with a new type of modular building unit, based upon a 1,8-platinum-functionalized anthracene, leads to the self-organization of rectangular frameworks. X-ray crystallography confirms the cyclic structure of the supramolecular cationic complexes. Spectral assignments were provided by 2D NOESY (1)H NMR experiments.

Archimedean solids: transition metal mediated rational self-assembly of supramolecular-truncated tetrahedra.

A family of nanoscale-sized supramolecular cage compounds with a polyhedral framework is prepared by self-assembly from tritopic building blocks and rectangular corner units via noncovalent coordination interactions. These highly symmetrical cage compounds are described as face-directed, self-assembled truncated tetrahedra with T(d) symmetry.

Preparation, characterization, and X-ray crystal structures of helical and syndiotactic zinc-based coordination polymers.

The reactions of (facac)2Zn.2H2O (facac = 1,1,1,5,5,5-hexafluoroacetylacetonate) with 2,5-bis(4-ethynylpyridyl)furan (1) and 1,2-bis(4-ethynylpyridyl)benzene (2) yield, upon crystallization, coordination polymers. The former polymer, ((facac)2Zn.1)n, has an isotactic, helical structure in the solid state [monoclinic space group P2(1)/n; a = 11.0374(3) A, b = 24.2179(10) A, c = 14.3970(4) A, beta = 92.880(2) degrees; Z = 4]. The latter polymer, ((facac)2Zn.2)n, adopts a syndiotactic structure in the solid state [monoclinic space group P2(1)/n; a = 9.1344(1) A, b = 21.7985(5) A, c = 16.0322(4) A, beta = 99.6680(11) degrees; Z = 4]. The solution structures of the corresponding oligomers have been studied by low-temperature 1H and 19F NMR spectroscopy. Chiral polymers were prepared using the fragment [(+)-tfc]2Zn ((+)-tfc = 3-((trifluoromethyl)hydroxymethylene)-(+)-camphorate). A linear, zigzag structure was found for ([(+)-tfc]2Zn.1)n [triclinic space group P1; a = 7.4833(2) A, b = 14.1563(5) A, c = 21.21230(5) A, alpha = 78.4440(15) degrees, beta = 81.5644(15) degrees, gamma = 76.4976(13) degrees; Z = 1]. Reaction with tris(4-pyridyl)methanol (3) yielded a homochiral, helical polymer, ([(+)-tfc]2Zn.3)n [monoclinic space group C2; a = 25.0633(12) A, b = 11.8768(7) A, c = 17.1205(9) A, alpha = 90 degrees, beta = 117.954(3) degrees, gamma = 90 degrees; Z = 4].

Self-assembly of nanoscale cuboctahedra by coordination chemistry.

Self-assembled polyhedral structures are common in biology. The coats of many viruses, for example, have a structure based on icosahedral symmetry. The preparation of synthetic polyhedral molecular assemblies represents a challenging problem, but supramolecular chemistry has now advanced to the point where the task may be addressed. Macromolecular and supramolecular entities of predefined geometric shape and with well-defined internal environments are potentially important for inclusion phenomena, molecular recognition and catalysis. Here we report the use of self-assembly of molecular units driven by coordination to transition-metal ions to prepare a cuboctahedron from 20 tridentate and bidentate subunits in a single step. The cuboctahedron is an archimedean semiregular polyhedron that combines square and triangular faces. Our self-assembled polyhedral capsules, characterized by NMR and electrospray mass spectrometry, are around 5 nanometres in diameter.

Molecular architecture via coordination: self-assembly of pseudohexagonal A2(3)X2(3)-macrocycles.

[formula: see text] The interaction of two complementary ditopic building blocks, each incorporating 120 degrees angles between the active coordination sites, in methylene chloride at room temperature results in the spontaneous self-assembly of platinum-based assemblies of hexagonal shape.

Alkynyl phosphates are potent inhibitors of serine enzyme.

Propynyl, hexynyl and t-butylethynyl diethyl phosphates were found to be very powerful covalent inhibitors of serine enzymes. Esterases were inhibited with second-order rate constants of 10(7)-10(8) m(-1) min(-1). Most proteases were inhibited with a rate constant of 10(4)-10(5) M(-1) min(-1). By inhibiting chymotrypsin with (3-14C)-1-propynyl diethyl phosphate, it was established that inhibition was caused by binding of the phosphate group to the enzyme active site.

Mechanism-based inactivation of phosphotriesterase by reaction of a critical histidine with a ketene intermediate.

Five alkynyl phosphate esters have been synthesized as probes of the active site structure of phosphotriesterase. These compounds have the potential to be converted by the enzyme to a highly reactive ketene intermediate which can then react with an active site nucleophile causing irreversible inhibition of the enzyme by formation of an inactive covalent adduct. All five compounds completely inactivate enzyme function in less than 15 s at pH 7.0. The partition rations of 1-hexynyl diethyl phosphate (I), 1-propynyl diethyl phosphate (II), 1-hexynyl diphenyl phosphate (III), 1-hexynyl dimethyl phosphate (IV), and ethynyl diethyl phosphate (V) fall in the range between 480 and 1700; thus, all five alkynyl phosphate esters work equally well as inactivators despite the differences in their structures. The rate constants for enzyme inactivation, kinact, are 1.7 s-1 with I, 1.3 s-1 with II, and 0.12 s-1 with IV. They compare well with the kcat for the Co-substituted phosphotriesterase; hence these compounds are good substrates. The stoichiometry of inhibitor bound to protein is 1:1, as determined by inactivation of the enzyme using the radiolabeled compound [3-14C]-1-propynyl diethyl phosphate. Addition of an exogenous nucleophile, azide, did not protect phosphotriesterase from being inactivated by the alkynyl phosphate esters, suggesting that the reactive intermediate produced from the inhibitor is not released from the enzyme surface prior to covalent labeling of the protein. Chemical and spectroscopic evidence suggests that a histidine residue is modified in the inactivation reaction. The inactivated phosphotriesterase can be reactivated by increasing the pH of the protein solution. N-Acylimidazoles are known to be easily hydrolyzed at alkaline pH values.(ABSTRACT TRUNCATED AT 250 WORDS)

Histidine-254 is essential for the inactivation of phosphotriesterase with the alkynyl phosphate esters and diethyl pyrocarbonate.

The alkynyl phosphate ester, 1-hexynyl diethyl phosphate (I), is a mechanism-based inhibitor of phosphotriesterase. It has been previously determined that a histidine residue in the wild-type phosphotriesterase is covalently modified by this compound. In order to identify which of the seven histidine residues in the native enzyme are required for inactivation, the kinetic properties of phosphotriesterase mutants with this suicide substrate were examined in detail. Six of the seven mutants (histidine to asparagine) were rapidly inactivated by I. The mutants H55N, H57N, and H230N also showed partition ratios that were lower than for the wild-type enzyme. The rate of inactivation of H201N was significantly slower than that of wild-type phosphotriesterase. The H254N mutant could not be inactivated; no more than 60% of the initial activity was lost, even at I/E0 ratios of 4000:1. These results suggest that His-254 is essential for the inactivation of phosphotriesterase and is likely to be the primary target in the wild-type enzyme for modification by I. The inactivation of wild-type phosphotriesterase and the seven mutants was also studied using diethyl pyrocarbonate, a histidine selective reagent. The second-order rate constant for the inactivation of wild-type phosphotriesterase was determined to be 1.3 M-1 min-1. The rate constants for the inactivation of the H55N, H57N, H201N, and H230N mutants were larger than for the wild-type enzyme. Thus, it appears that when these histidine residues are replaced by asparagine, other histidine residues in the active site become more susceptible to modification, resulting in a faster rate of inactivation. The mutant H254N was not inactivated in the presence of DEPC.(ABSTRACT TRUNCATED AT 250 WORDS)

The interaction of alkynyl carboxylates with serine enzymes. A potent new class of serine enzyme inhibitors.

The recently reported alkynyl esters, propynyl benzoate and propynyl p-methoxybenzoate, were found to interact with a variety of serine enzymes. alpha-Chymotrypsin was inhibited very rapidly by an equivalent amount of the esters. Trypsin, elastase and pronase were also inhibited by the esters. On the other hand, liver esterase started to hydrolyze the alkynyl esters rapidly, but the enzyme became inhibited during the course of reaction. The inhibited enzymes exhibited slow reactivation which could be considerably enhanced by hydroxylamine.

Synthesis and antitumor activity of simple vinyl and alpha-methylene-gamma-butyrolactone sulfonate esters and silyl enol ethers.

A number of simple silyl enol ethers and vinyl trifluoromethanesulfonates, a relatively new class of organic compounds capable of undergoing alkylation by a nucleophilic addition-elimination process, were evaluated in the P388 lymphocytic leukemia system. No activity (ILS = 8-22%) was observed in the simple vinyl derivatives. Some activity (ILS = 20-42%) was observed for a series of siloxy and sulfonate (CH3SO2 and CF3SO3) functionalized alpha-methylene lactone systems. The enhanced activity of the functionalized systems over the parent methylene lactone is ascribed to a possible irreversible alkylation by cellular nucleophiles via a nucleophilic addition-elimination process.