Enhancing itaconic acid production by Aspergillus terreus

Aspergillus terreus is successfully used for industrial production of itaconic acid. The acid is formed from cis-aconitate, an intermediate of the tricarboxylic (TCA) cycle, by catalytic action of cis-aconitate decarboxylase. It could be assumed that strong anaplerotic reactions that replenish the pool of the TCA cycle intermediates would enhance the synthesis and excretion rate of itaconic acid. In the phylogenetic close relative Aspergillus niger, upregulated metabolic flux through glycolysis has been described that acted as a strong anaplerotic reaction. Deregulated glycolytic flux was caused by posttranslational modification of 6-phosphofructo-1-kinase (PFK1) that resulted in formation of a highly active, citrate inhibition-resistant shorter form of the enzyme. In order to avoid complex posttranslational modification, the native A. niger pfkA gene has been modified to encode for an active shorter PFK1 fragment. By the insertion of the modified A. niger pfkA genes into the A. terreus strain, increased specific productivities of itaconic acid and final yields were documented by transformants in respect to the parental strain. On the other hand, growth rate of all transformants remained suppressed which is due to the low initial pH value of the medium, one of the prerequisites for the accumulation of itaconic acid by A. terreus mycelium. © 2010 Springer-Verlag.

4-Chloroanilinium 2-carboxy-4,5-dichlorobenzoate

The structure of the 1:1 proton-transfer compound of 4-chloroaniline with 4,5-dichlorophthalic acid (DCPA), viz. C6H7ClN+ C8H3Cl2O4-, has been determined at 130 K. The non-planar hydrogen phthalate anions and the 4-chloroanilinium cations form two-dimensional O-H...O and N-H...O hydrogen-bonded substructures which have no peripheral extension. Between the sheets there are weak \p--\p associations between alternating cation--anion aromatic ring systems [shortest centroid separation, 3.735(4)A].

1,10-phenanthrolin-1-ium 2-carboxy-4,5-dichlorobenzoate

In the structure of the 1:1 proton-transfer compound of 1,10-phenanthroline with 4,5-dichlorophthalic acid, C12H9N2+ C8H3Cl2O4-, determined at 130 K, the 1,10-phenanthroline cation and the hydrogen 4,5-dichlorophthalate anion associate through a single N-H...O(carboxyl) hydrogen bond giving discrete units which have no extension except through a number of weak cation C-H...O(anion) associations and weak cation--anion aromatic ring pi-pi interactions [minimum centroid separation, 3.6815(12)A]. The anions are essentially planar [maximum deviation 0.214(1)A (a carboxyl O)] with the syn-related H atom of the carboxyl group forming a short intramolecular O-H...O(carboxyl) hydrogen bond.

Unusual hydrate stabilization in the two-dimensional layered structure of quinacrinium bis(2-carboxy-4,5-dichlorobenzoate) tetrahydrate, a proton-transfer compound of the drug quinacrine

The crystal structure of the hydrated proton-transfer compound of the drug quinacrine [rac-N'-(6-chloro-2-methoxyacridin-9-yl)-N,N-diethylpentane-1,4-diamine] with 4,5-dichlorophthalic acid, C23H32ClN3O2+ . 2(C8H3Cl2O4-).4H2O (I), has been determined at 200 K. The four labile water molecules of solvation form discrete ...O--H...O--H... hydrogen-bonded chains parallel to the quinacrine side chain, the two N--H groups of which act as hydrogen-bond donors for two of the water acceptor molecules. The other water molecules, as well as the acridinium H atom, also form hydrogen bonds with the two anion species and extend the structure into two-dimensional sheets. Between these sheets there are also weak cation--anion and anion--anion pi-pi aromatic ring interactions. This structure represents only the third example of a simple quinacrine derivative for which structural data are available but differs from the other two in that it is unstable in the X-ray beam due to efflorescence, probably associated with the destruction of the unusual four-membered water chain structures.

4-(2-hydroxyethyl)anilinium 3-carboxy-4-hydroxybenzenesulfonate monohydrate

In the structure of the title compound C8H12NO+ C7H5O6S- . H2O, from the reaction of 2-(4-aminophenyl)ethanol with 5-sulfosalicylic acid, the cations form head-to-tail hydrogen-bonded chains through C1/1(9) anilinium N+-H...O(hydroxyl} interactions while the anions also form similar but C1/1(8)-linked chains through carboxylic acid O-..O(sulfonate) interactions. The chains inter-associate through a number of N-H...O and O-H...O bridging interactions giving a two-dimensional array in the ab plane.

Isopropylaminium 2-carboxy-4, 5-dichlorobenzoate

In the structure of the 1:1 proton-transfer compound of isopropylamine with 4,5-dichlorophthalic acid, C3H10N+·C8H3Cl2O4-, the three cation H-atom donors associate with three separate carboxyl O-atom anion acceptors, giving conjoint cyclic R44(12), R44(16) hydrogen-bonding cation-anion interactions in a one-dimensional ribbon structure. In the anions, the carboxyl groups lie slightly out of the plane of the benzene ring [maximum deviations = 0.439 (1) for a carboxylic acid O atom and 0.433 (1) Å for a carboxylate O atom]. However, the syn-related proton of the carboxylic acid group forms the common short intramolecular O-HOcarboxyl hydrogen bond.

The structure of the copper(II) complex with 4,5-dichlorophthalic acid: The 1:1 complex 'adduct' salt trans-tetraaqua(2-carboxy-4,5-dichlorobenzoato)(4,5-dichlorobenzene-1,2-dicarboxylic acid)copper(II) 2-carboxy-4,5-dichlorobenzoate

The unusual (1:1) complex ‘adduct’ salt of copper(II) with 4,5-dichlorophthalic acid (H2DCPA), having formula [Cu(H2O)4(C8H3Cl2O4) (C8H4Cl2O4)] . (C8H3Cl2O4) has been synthesized and characterized using single-crystal X-ray diffraction. Crystals are monoclinic, space group P21/c, with Z = 4 in a cell with dimensions a = 20.1376(7), b =12.8408(4) c = 12.1910(4) Å, β = 105.509(4)o. The complex is based on discrete tetragonally distorted octahedral [CuO6] coordination centres with the four water ligands occupying the square planar sites [Cu-O, 1.962(4)-1.987(4) Å] and the monodentate carboxyl-O donors of two DCPA ligand species in the axial sites. The first of these bonds [Cu-O, 2.341(4) Å] is with an oxygen of a HDCPA monoanion, the second with an oxygen of a H2DCPA acid species [Cu-O, 2.418(4) Å]. The un-coordinated ‘adduct’ molecule is a HDCPA counter anion which is strongly hydrogen-bonded to the coordinated H2DCPA ligand [O… O, 2.503(6) Å] while a number of peripheral intra- and intermolecular hydrogen-bonding interactions give a two-dimensional network structure.

4-Methylpyridinium 2-carboxy-4,5-dichlorobenzoate

In the structure of the 1:1 proton-transfer compound of 4-methylpyridine (\g-picoline) with 4,5-dichlorophthalic acid, C6H8N+ C8H3Cl2O4- . H2O, determined at 200 K, the 4,5-dichlorophthalate anions are bridged by the water molecule through O--H...O~carboxyl~ hydrogen bonds, giving zig-zag chains which extend along the c axial direction of the unit cell. The 4-methylpyridine cations are linked to the chains through single N--H...O~water~ hydrogen bonds and occupy the voids within the chains in the one-dimensional structure. The anions have the common 'planar' conformation with the short intramolecular O--H...O(carboxyl) hydrogen bond.

Anhydrous 1:1 proton-transfer compounds of isonipecotamide with picric acid and 3,5-dinitrosalicylic acid: 4-carbamoylpiperidinium 2,4,6-trinitrophenolate and two polymorphs of 4-carbamoylpiperidinium 2-carboxy-4,6-dinitrophenolate

The structures of the anhydrous 1:1 proton-transfer compounds of isonipecotamide (4-carbamoylpiperidine) with picric acid and 3,5-dinitrosalicylic acid, namely 4-carbamoylpiperidinium 2,4,6-trinitrophenolate, C6H13N2O8+ C6H2N3O7- (I) and 4-carbamoylpiperidinium 2-carboxy-4,6-dinitrophenolate, C6H13N2O8+ C7H3N2O7-: two forms, the monoclinic alpha-polymorph (II) and the triclinic beta-polymorph (III) have been determined at 200 K. All compounds form hydrogen-bonded structures, one-dimensional in (II), two-dimensional in (I) and three-dimensional in (III). In (I), the cations form centrosymmetric cyclic head-to-tail hydrogen-bonded homodimers [graph set R2/2(14)] through lateral duplex piperidinium N---H...O(amide) interactions. These dimers are extended into a two-dimensional network structure through further interactions with anion phenolate-O and nitro-O acceptors, including a direct symmetric piperidinium N-H...O(phenol),O(nitro) cation--anion association [graph set R2/1(6)]. The monoclinic polymorph (II) has a similar R2/1(6) cation-anion hydrogen-bonding interaction to (I) but with an additional conjoint symmetrical R1/2(4) interaction as well as head-to-tail piperidinium N-H...O(amide) O hydrogen bonds and amide N-H...O(carboxyl) hydrogen bonds, give a network structure which include large R3/4(20) rings. The hydrogen bonding in the triclinic polymorph (III) is markedly different from that of monoclinic (II). The asymmetric unit contains two independent cation-anion pairs which associate through cyclic piperidinium N-H...O,O'(carboxyl) interactions [graph set R2/1(4)]. The cations also show the zig-zag head-to-tail piperidinium N-H...O(amide) hydrogen-bonded chain substructures found in (II) but in addition feature amide N-H...O(nitro) and O(phenolate) and amide N-H...O(nitro) associations. As well there is a centrosymmetric double-amide N-H...O(carboxyl) bridged bis(cation-anion) ring system [graph set R2/4(8)] in the three-dimensional framework. The structures reported here demonstrate the utility of the isonipecotamide cation as a synthon with previously unrecognized potential for structure assembly applications. Furthermore, the structures of the two polymorphic 3,5-dinitrosalicylic acid salts show an unusual dissimilarity in hydrogen-bonding characteristics, considering that both were obtained from identical solvent systems.

Hexaaquamagnesium bis(3-carboxy-4-hydroxybenzenesulfonate) dihydrate

In the structure of the title compound, [Mg(H2O)6]2+ 2(C7H5O6S-). 2(H2O), the octahedral complex cations lie on crystallographic inversion centres and are hydrogen-bonded through the coordinated waters to the substituted benzenesulfonate monoanions and the water molecules of solvation, and together with a carboxylic acid O-H...O(sulfonate) association, give a three-dimensional structure.

tert-Butylaminium 2-carboxy-4,5-dichlorobenzoate

In the structure of the title anhydrous salt C4H12N+ C8H3Cl2O4-, the 4,5-dichlorophthalate monoanions have the common 'planar' conformation with the carboxyl groups close to coplanar with the benzene ring and with a short intramolecular carboxylic acid O-H...O hydrogen bond. A two-dimensional sheet structure is formed through aminium N-H...O(carboxyl) hydrogen-bonding associations.

4-(4-Nitrobenzyl)pyridinium 3-carboxy-4-hydroxybenzenesulfonate

In the title salt, C12H11N2O2+·C7H5O6S-, the dihedral angle between the benzene and pyridine rings in the 4-(4-nitrobenzyl)pyridinium cation is 82.7 (2)°. Within the anion there is an intramolecular hydroxy-O-HO(carboxylic acid) bond. In the crystal, the cation forms a single N+-HOsulfonate hydrogen bond with the anion. These cation-anion pairs interact through duplex anion carboxylic acid O-HOsulfonate hydrogen bonds, giving a centrosymmetric cyclic association [graph set R22(16)]. The crystals studied were non-merohedrally twinned.

2-(4-Aminobenzenesulfonamido)-4,6-dimetylpyrimidin-1-ium 2-carboxy-4,6-dinitrophenolate

In the structure of the of the phenolate salt of the sulfa drug sulfamethazine with 3,5-dinitrosalicylic acid, C12H15N4O2S+ C7H3N2O7-, the dihedral angle between the pyrimidine and phenyl rings of the cation is 59.70(17)\%. Cation--anion hydrogen-bonding interactions involving pyrimidine N+-H...O(carboxyl) and amine N-H...O(carboxyl) pairs give a cyclic R2/2(8) motif while secondary N-H...O hydrogen bonds between the aniline group and both sulfone and nitro O-atom acceptors give a two-dimensional structure extending along (001).

Approaches to the Synthesis of a Water-soluble Carboxy Nitroxide

The robust and diversely useful isoindoline nitroxide, 5-carboxy-1,1,3,3-tetramethylisoindolin-2-yloxyl (1; CTMIO), has previously been synthesised in low-to-moderate yields from phthalic anhydride (3). Recent interest in its biological potential as a potent antioxidant and in other areas has seen an increased demand for its production. Herein, three new synthetic routes to CTMIO are presented and their efficiencies assessed. Two routes, via the nitrile 9 and the formyl compound 11, derive from 5-bromo-1,1,3,3-tetramethylisoindoline (6). The third approach starts from the readily accessible starting material, 4-methylphthalic anhydride (12), and proceeds by a methylarene oxidation with potassium permanganate. The three new approaches yield CTMIO in comparable overall yields (16–18 %); however, the synthetic efficiency is most improved when employing the nitrile intermediate 9.

Hydrogen bonding in two ammonium salts of 5-sulfosalicylic acid : ammonium 3-carboxy-4-hydroxybenzenesulfonate monohydrate and triammonium 3-carboxy-4-hydroxybenzenesulfonate 3-carboxylato-4-hydroxybenzenesulfonate

The structures of two ammonium salts of 3-carboxy-4-hydroxybenzenesulfonic acid (5-sulfosalicylic acid, 5-SSA) have been determined at 200 K. In the 1:1 hydrated salt, ammonium 3-carboxy-4-hydroxybenzenesulfonate monohydrate, NH4+·C7H5O6S-·H2O, (I), the 5-SSA- monoanions give two types of head-to-tail laterally linked cyclic hydrogen-bonding associations, both with graph-set R44(20). The first involves both carboxylic acid O-HOwater and water O-HOsulfonate hydrogen bonds at one end, and ammonium N-HOsulfonate and N-HOcarboxy hydrogen bonds at the other. The second association is centrosymmetric, with end linkages through water O-HOsulfonate hydrogen bonds. These conjoined units form stacks down c and are extended into a three-dimensional framework structure through N-HO and water O-HO hydrogen bonds to sulfonate O-atom acceptors. Anhydrous triammonium 3-carboxy-4-hydroxybenzenesulfonate 3-carboxylato-4-hydroxybenzenesulfonate, 3NH4+·C7H4O6S2-·C7H5O6S-, (II), is unusual, having both dianionic 5-SSA2- and monoanionic 5-SSA- species. These are linked by a carboxylic acid O-HO hydrogen bond and, together with the three ammonium cations (two on general sites and the third comprising two independent half-cations lying on crystallographic twofold rotation axes), give a pseudo-centrosymmetric asymmetric unit. Cation-anion hydrogen bonding within this layered unit involves a cyclic R33(8) association which, together with extensive peripheral N-HO hydrogen bonding involving both sulfonate and carboxy/carboxylate acceptors, gives a three-dimensional framework structure. This work further demonstrates the utility of the 5-SSA- monoanion for the generation of stable hydrogen-bonded crystalline materials, and provides the structure of a dianionic 5-SSA2- species of which there are only a few examples in the crystallographic literature.