Novel cocrystals of the potent 1,2,4-thiadiazole-based neuroprotector with carboxylic acids: virtual screening, crystal structures and solubility performance

2021 ◽  
Vol 45 (6) ◽  
pp. 3034-3047
Author(s):  
Artem O. Surov ◽  
Alexander P. Voronin ◽  
Nikita A. Vasilev ◽  
Andrey B. Ilyukhin ◽  
German L. Perlovich
Keyword(s):  
Virtual Screening ◽  
Crystal Structures ◽  
Carboxylic Acids ◽  
Biologically Active ◽  
Thiadiazole Derivative ◽  
Hydroxybenzoic Acids ◽  
Cocrystal Screening

Five new multicomponent solid forms of the biologically active 1,2,4-thiadiazole derivative (TDZH) with dicarboxylic and hydroxybenzoic acids have been discovered by combined virtual/experimental cocrystal screening.

scholarly journals Crystal structures of non-oxidative decarboxylases reveal a new mechanism of action with a catalytic dyad and structural twists

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Matthias Zeug ◽  
Nebojsa Markovic ◽  
Cristina V. Iancu ◽  
Joanna Tripp ◽  
Mislav Oreb ◽  
...  
Keyword(s):  
Crystal Structures ◽  
Active Site ◽  
Enzyme Engineering ◽  
Base Catalysis ◽  
Oxidative Decarboxylation ◽  
Transition State Stabilization ◽  
Major Bottleneck ◽  
Hydroxybenzoic Acids ◽  
Potassium Binding ◽  
Β Sheet

AbstractHydroxybenzoic acids, like gallic acid and protocatechuic acid, are highly abundant natural compounds. In biotechnology, they serve as critical precursors for various molecules in heterologous production pathways, but a major bottleneck is these acids’ non-oxidative decarboxylation to hydroxybenzenes. Optimizing this step by pathway and enzyme engineering is tedious, partly because of the complicating cofactor dependencies of the commonly used prFMN-dependent decarboxylases. Here, we report the crystal structures (1.5–1.9 Å) of two homologous fungal decarboxylases, AGDC1 from Arxula adenivorans, and PPP2 from Madurella mycetomatis. Remarkably, both decarboxylases are cofactor independent and are superior to prFMN-dependent decarboxylases when heterologously expressed in Saccharomyces cerevisiae. The organization of their active site, together with mutational studies, suggests a novel decarboxylation mechanism that combines acid–base catalysis and transition state stabilization. Both enzymes are trimers, with a central potassium binding site. In each monomer, potassium introduces a local twist in a β-sheet close to the active site, which primes the critical H86-D40 dyad for catalysis. A conserved pair of tryptophans, W35 and W61, acts like a clamp that destabilizes the substrate by twisting its carboxyl group relative to the phenol moiety. These findings reveal AGDC1 and PPP2 as founding members of a so far overlooked group of cofactor independent decarboxylases and suggest strategies to engineer their unique chemistry for a wide variety of biotechnological applications.

Triethanolammonium salts of biologically active carboxylic acids

2015 ◽  
Vol 85 (12) ◽  
pp. 2710-2714 ◽  
Author(s):  
Yu. A. Kondratenko ◽  
T. A. Kochina ◽  
V. S. Fundamensky ◽  
Yu. G. Vlasov
Keyword(s):  
Carboxylic Acids ◽  
Biologically Active ◽  
Biologically Active Carboxylic Acids

scholarly journals Mass Spectral Studies of the Biologically Active Stereoisomer Family of e,e,e-(Methanofullerene(60-63)-Carboxylic Acids

2018 ◽  
Vol 14 (4) ◽  
pp. 406-415
Author(s):  
Michael Grayson ◽  
Joshua Hardt ◽  
Michael Gross ◽  
Subhasish K. Chakraborty ◽  
Laura Dugan
Keyword(s):  
Carboxylic Acids ◽  
Biologically Active ◽  
Spectral Studies ◽  
Mass Spectral

Saccharin salts of biologically active hydrazone derivatives

2015 ◽  
Vol 39 (11) ◽  
pp. 8614-8622 ◽  
Author(s):  
Artem O. Surov ◽  
Alexander P. Voronin ◽  
Anna A. Simagina ◽  
Andrei V. Churakov ◽  
Sophia Y. Skachilova ◽  
...  
Keyword(s):  
Crystal Structures ◽  
Biologically Active ◽  
Formation Thermodynamics

Crystal structures, solubility and formation thermodynamics of saccharin salts with biologically active hydrazone derivatives were investigated.

Hydrogen Bonds in "Carboxyoximes": the Case of Bomane Derivatives

2000 ◽  
Vol 55 (8) ◽  
pp. 677-684 ◽  
Author(s):  
Maciej Kubicki ◽  
Teresa Borowiak ◽  
Wiesław Z. Antkowiak
Keyword(s):  
Carboxylic Acid ◽  
Hydrogen Bonds ◽  
Crystal Structures ◽  
Carboxylic Acids ◽  
Supramolecular Structures ◽  
X Ray Diffraction ◽  
X Ray ◽  
Carboxylic Groups ◽  
Acid Function

Abstract The tendency of forming mixed carboxyl-to-oxime hydrogen bonds was tested on the series of bornane derivatives: one with the acid function only (bornane-2-endo-carboxylic acid), one with the oxime function (2,2′-diethylthiobomane-3-oxime), and one with both oxime and carboxylic functions (bornane-2-oxime-3-endo-carboxylic acid). The crystal structures of these compounds were determined by means of X-ray diffraction. In bornane-2-endo-carboxylic acid and 2,2′-diethylthiobornane-3-oxime 'homogenic' hydrogen bonds were found, and these hydrogen bonds close eight-and six-membered rings, respectively. By contrast, in bornane-2-oxime-3-endo-carboxylic acid 'heterogenic' hydrogen bonds between carboxylic and oxime bonds were found. This carboxylic-oxime, or 'carboxyoxime' system is almost always present in compounds which have both oxime and carboxylic groups; therefore it can be regarded as an element of supramolecular structures (synthon). The presence of such synthons can break the tendency of carboxylic acids and oximes towards crystallizing in centrosymmetric structures.

scholarly journals A Simple and Mild Microwave-Based Synthesis of Novel Functionalized Benzofulvenes

SynOpen ◽  
2018 ◽  
Vol 02 (03) ◽  
pp. 0256-0262
Author(s):  
Adam Glass ◽  
Katherine Caspary ◽  
Cole Fisher ◽  
Connor Whyte ◽  
James Okubo ◽  
...  
Keyword(s):  
Crystal Structures ◽  
Microwave Heating ◽  
Good Yield ◽  
Optoelectronic Devices ◽  
Biologically Active ◽  
Synthetic Method ◽  
Polymer Precursors ◽  
Coupling Techniques

Benzofulvenes and their derivatives are useful molecular entities having applications as biologically active molecules, polymer precursors, and optoelectronic devices. We have developed a simple and mild synthetic method for the formulation of a variety of these interesting compounds. Using carbonyl coupling techniques combined with microwave heating, a wide variety of functionalized benzofulvenes can be accessed rapidly in good yield. Furthermore, we have obtained five crystal structures further expanding a limited number of benzofulvene structures available.

Cocrystals of Penciclovir with Hydroxybenzoic Acids: Synthesis, Crystal Structures, and Physicochemical Evaluation

2020 ◽  
Vol 20 (6) ◽  
pp. 4108-4119 ◽  
Author(s):  
Zhao-Jun Yuan ◽  
Xia-Lin Dai ◽  
Yong-Liang Huang ◽  
Tong-Bu Lu ◽  
Jia-Mei Chen
Keyword(s):  
Crystal Structures ◽  
Physicochemical Evaluation ◽  
Hydroxybenzoic Acids
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