The LarB carboxylase/hydrolase forms a transient cysteinyl-pyridine intermediate during nickel-pincer nucleotide cofactor biosynthesis

Enzymes possessing the nickel-pincer nucleotide (NPN) cofactor catalyze C2 racemization or epimerization reactions of α-hydroxyacid substrates. LarB initiates synthesis of the NPN cofactor from nicotinic acid adenine dinucleotide (NaAD) by performing dual reactions: pyridinium ring C5 carboxylation and phosphoanhydride hydrolysis. Here, we show that LarB uses carbon dioxide, not bicarbonate, as the substrate for carboxylation and activates water for hydrolytic attack on the AMP-associated phosphate of C5-carboxylated-NaAD. Structural investigations show that LarB has an N-terminal domain of unique fold and a C-terminal domain homologous to aminoimidazole ribonucleotide carboxylase/mutase (PurE). Like PurE, LarB is octameric with four active sites located at subunit interfaces. The complex of LarB with NAD+, an analog of NaAD, reveals the formation of a covalent adduct between the active site Cys221 and C4 of NAD+, resulting in a boat-shaped dearomatized pyridine ring. The formation of such an intermediate with NaAD would enhance the reactivity of C5 to facilitate carboxylation. Glu180 is well positioned to abstract the C5 proton, restoring aromaticity as Cys221 is expelled. The structure of as-isolated LarB and its complexes with NAD+ and the product AMP identify additional residues potentially important for substrate binding and catalysis. In combination with these findings, the results from structure-guided mutagenesis studies lead us to propose enzymatic mechanisms for both the carboxylation and hydrolysis reactions of LarB that are distinct from that of PurE.

Skeletal remodeling of chalcone-based pyridinium salts to access isoindoline polycycles and their bridged derivatives

Simultaneous deconstructive ring-opening and skeletal reconstruction of an inert, aromatic pyridinium ring is of great importance in synthetic communities. However, research in this area is still in its infancy. Here,...

Binding Modes of a Phenylpyridinium Styryl Fluorescent Dye with Cucurbiturils

In order to explore how cucurbituril hosts accommodate an N-phenyl-pyridinium derivative guest, the complexation of the solvatochromic dye, 4-(4-(dimethylamino)styryl)-1-phenylpyridinium iodide (PhSt) with α,α′,δ,δ′-tetramethyl-cucurbit[6]uril (Me4CB6) and cucurbit[7]uril (CB7) was investigated by absorption spectroscopic, fluorescence and NMR experiments. In aqueous solutions, PhSt forms 1:1 complexes with both cucurbiturils, the complex with CB7 has a higher stability constant (Ka = 6.0 × 106 M−1) than the complex with Me4CB6 (Ka = 1.1 × 106 M−1). As revealed by NMR experiments and confirmed by theoretical calculations, CB7 encapsulates the whole phenylpyridinium entity of the PhSt cation guest, whereas the cavity of Me4CB6 includes only the phenyl ring, the pyridinium ring is bound to the carbonyl rim of the host. The binding of PhSt to cucurbiturils is accompanied by a strong enhancement of the fluorescence quantum yield due to the blocking of the deactivation through a twisted intramolecular charge transfer (TICT) state. The TICT mechanism in PhSt was characterized by fluorescence experiments in polyethylene glycol (PEG) solvents of different viscosities. The PhSt-CB7 system was tested as a fluorescence indicator displacement (FID) assay, and it recognized trimethyl-lysine selectively over other lysine derivatives.

A pyridinium anionic ring-opening reaction applied to the stereodivergent syntheses of Piperaceae natural products

Expanding the scope of a pyridinium ring-opening reaction, a practical oxidation protocol has been devised to access isomerically pure bromodiene esters. The utility is demonstrated in a divergent strategy to obtain two natural TRPV1 agonist motifs.

Crystal structure and Hirshfeld surface analysis of 2-aminopyridinium hydrogen phthalate

Aminopyridine and phthalic acid are well known synthons for supramolecular architectures for the synthesis of new materials for optical applications. The 2-aminopyridinium hydrogen phthalate title salt, C5H7N2 +·C8H5O4 −, crystallizes in the non-centrosymmetric space group P21. The nitrogen atom of the –NH2 group in the cation deviates from the fitted pyridine plane by 0.035 (7) Å. The plane of the pyridinium ring and phenyl ring of the anion are oriented at an angle of 80.5 (3)° to each other in the asymmetric unit. The anion features a strong intramolecular O—H...O hydrogen bond, forming a self-associated S(7) ring motif. The crystal packing is dominated by intermolecular N—H...O hydrogen bonds leading to the formation of 21 helices, with a C(11) chain motif. They propagate along the b axis and enclose R 2 2(8) ring motifs. The helices are linked by C—H...O hydrogen bonds, forming layers parallel to the ab plane. Hirshfeld surface analysis and two-dimensional fingerprint plots were used to investigate and quantify the intermolecular interactions in the crystal.

Hexaaquazinc(II) dinitrate bis[5-(pyridinium-3-yl)tetrazol-1-ide]

Hexaaquazinc(II) dinitrate 5-(pyridinium-3-yl)tetrazol-1-ide, [Zn(H2O)6](NO3)2·2C6H5N5, crystallizes in the space group P\overline{1}. The asymmetric unit contains one zwitterionic 5-(pyridinium-3-yl)tetrazol-1-ide molecule, one NO3 − anion and one half of a [Zn(H2O)6]2+ cation (\overline{1} symmetry). The pyridinium and tetrazolide rings in the zwitterion are nearly coplanar, with a dihedral angle of 5.4 (2)°. Several O—H...N and N—H...O hydrogen-bonding interactions exist between the [Zn(H2O)6]2+ cation and the N atoms of the tetrazolide ring, and between the nitrate anions and the N—H groups of the pyridinium ring, respectively, giving rise to a three-dimensional network. The 5-(pyridinium-3-yl)tetrazol-1-ide molecules show parallel-displaced π–π stacking interactions; the centroid–centroid distance between adjacent tetrazolide rings is 3.6298 (6) Å and that between the pyridinium and tetrazolide rings is 3.6120 (5) Å.

Toxicological study of some ionic liquids

The increasing interest in the development of new environment-friendly solvents has led to the synthesis of new materials that minimize the impact of solvents on the environment. However, most of the published studies on green solvents focus primarily on their physicochemical properties, with limited emphasis on their toxicological risk in the environment. In this study, the acute toxicities of five ionic liquids, 1-propylpyridinium tetrafluoroborate, 1-butylpyridinium tetrafluoroborate, 1-butyl-2-methylpyridinium tetrafluoroborate, 1-butyl-3-methylpyridinium tetrafluoroborate and 1-butyl-4-methylpyridinium tetrafluoroborate, on Vibrio fischeri and Daphnia magna are evaluated. In the latter bioassay, the presence and position of a methyl group on the pyridinium ring or the length of the chain attached to the nitrogen atom seem to be the key factors for toxicity. In the Vibrio fischeri study, the alkyl chain attached to the nitrogen atom has a considerable influence on EC50 values. Moreover, quantitative structure activity relationship studies are performed to relate their physicochemical properties with their acute toxicity.

Crystal structure, thermal and fluorescence properties of 2,2′:6′,2′′-terpyridine-1,1′,1′′-triium tetrachloridonickelate(II) chloride

The title compound, (C15H14N3)[NiCl4]Cl, comprises an NiIIcation tetrahedrally coordinated by four chloride anions, a non-coordinating chloride anion and an essentially planar terpyridinium trication (tpyH33+), in which the central pyridinium ring forms dihedral angles of 5.7 (2) and 6.0 (2)° with the peripheral pyridinium rings. Three inter-species N—H...Cl hydrogen bonds are formed with the Cl−anion, which also forms a link between the (tpyH33+) cations through an aromatic C—H...Cl interaction, forming a zigzag chain extending along the 21(b) screw axis. Two of the anionic Cl atoms of the [NiCl4]2−anions form Ni—Cl...π interactions with separate pyridinium rings [Ni...Cg= 3.669 (3) and 3.916 (4) Å]. In the crystal, successive undulating inorganic and organic layers are formed, extending across the (100) plane. Thermogravimetric and differential thermal analysis (TGA/DTA) indicate that the compound starts to decompose at 313 K and may be a candidate for use as a blue-light luminescent material.

2-[Tris(pyridin-2-yl)methyl]pyridiniumtrans-bis(acetonitrile)tetrachloridoruthenate(III) acetonitrile monosolvate

The asymmetric unit of the title compound, [(C5H4N)3C(C5H5N)][RuCl4(CH3CN)2]·CH3CN, contains one 2-[tris(pyridin-2-yl)methyl]pyridinium cation, onetrans-bis(acetonitrile)tetrachloridoruthenate(III) anion and one acetonitrile solvent molecule. The RuIIIion is coordinated by four Cl−anions in the equatorial plane and by two acetonitrile ligands in the axial positions, forming a distorted octahedral geometry. The cation, the monoprotonated species of tetrakis(pyridin-2-yl)methane, forms an intramolecular N—H...N hydrogen bond between the pyridinium ring and one of the pyridine rings. The complex anions are linked to each otherviaC—H...Cl hydrogen bonds, forming an undulating sheet parallel to theacplane. A C—H...N hydrogen bond between the cation and the anion is also observed. The solvate acetonitrile molecule forms C—H...N and C—H...Cl hydrogen bonds, respectively, with the cation and the anion.