Hydrogen Bonding and Polymorphism of Amino Alcohol Salts with Quinaldinate: Structural Study.

Three amino alcohols, 3-amino-1-propanol (abbreviated as 3a1pOH), 2-amino-1-butanol (2a1bOH), and 2-amino-2-methyl-1-propanol (2a2m1pOH), were reacted with quinoline-2-carboxylic acid, known as quinaldinic acid. This combination yielded three salts, (3a1pOHH)quin (1, 3a1pOHH+ = protonated 3-amino-1-propanol, quin- = anion of quinaldinic acid), (2a1bOHH)quin (2, 2a1bOHH+ = protonated 2-amino-1-butanol), and (2a2m1pOHH)quin (3, 2a2m1pOHH+ = protonated 2-amino-2-methyl-1-propanol). The 2-amino-1-butanol and 2-amino-2-methyl-1-propanol systems produced two polymorphs each, labeled 2a/2b and 3a/3b, respectively. The compounds were characterized by X-ray structure analysis on single-crystal. The crystal structures of all consisted of protonated amino alcohols with NH3+ moiety and quinaldinate anions with carboxylate moiety. The used amino alcohols contained one OH and one NH2 functional group, both prone to participate in hydrogen bonding. Therefore, similar connectivity patterns were expected. This proved to be true to some extent as all structures contained the NH3+∙∙∙-OOC heterosynthon. Nevertheless, different hydrogen bonding and π∙∙∙π stacking interactions were observed, leading to distinct connectivity motifs. The largest difference in hydrogen bonding occurred between polymorphs 3a and 3b, as they had only one heterosynton in common.

Fine Tuning of Cholinesterase and Glutathione-S-Transferase Activities by Organoruthenium(II) Complexes.

Cholinesterases (ChEs) show increased activities in patients with Alzheimer's disease, and remain one of the main therapeutic targets for treatment of this neurodegenerative disorder. A library of organoruthenium(II) complexes was prepared to investigate the influence of their structural elements on inhibition of ChEs, and on another pharmacologically important group of enzymes, glutathione S-transferases (GSTs). Two groups of organoruthenium(II) compounds were considered: (i) organoruthenium(II) complexes with p-cymene as an arene ligand, and (ii) organoruthenium(II) carbonyl complexes as CO-releasing molecules. Eight organoruthenium complexes were screened for inhibitory activities against ChEs and GSTs of human and animal origins. Some compounds inhibited all of these enzymes at low micromolar concentrations, while others selectively inhibited either ChEs or GSTs. This study demonstrates the importance of the different structural elements of organoruthenium complexes for their inhibitory activities against ChEs and GSTs, and also proposes some interesting compounds for further preclinical testing as ChE or GST inhibitory drugs.

Beyond the Simple Copper(II) Coordination Chemistry with Quinaldinate and Secondary Amines.

Copper(II) acetate has reacted in methanol with quinaldinic acid (quinoline-2-carboxylic acid) to form [Cu(quin)2(CH3OH)]∙CH3OH (1) (quin- = an anionic form of the acid) with quinaldinates bound in a bidentate chelating manner. In the air, complex 1 gives off methanol and binds water. The conversion was monitored by IR spectroscopy. The aqua complex has shown a facile substitution chemistry with alicyclic secondary amines, pyrrolidine (pyro), and morpholine (morph). trans-[Cu(quin)2(pyro)2] (2) and trans-[Cu(quin)2(morph)2] (4) were obtained in good yields. The morpholine system has produced a by-product, trans-[Cu(en)2(H2O)2](morphCOO)2 (5) (morphCOO- = morphylcarbamate), a result of the copper(II) quinaldinate reaction with ethylenediamine (en), an inherent impurity in morpholine, and the amine reaction with carbon dioxide. (pyroH)[Cu(quin)2Cl] (3) forms on the recrystallization of [Cu(quin)2(pyro)2] from dichloromethane, confirming a reaction between amine and the solvent. Similarly, a homologous amine, piperidine (pipe), and dichloromethane produced (pipeH)[Cu(quin)2Cl] (11). The piperidine system has afforded both mono- and bis-amine complexes, [Cu(quin)2(pipe)] (6) and trans-[Cu(quin)2(pipe)2] (7). The latter also exists in solvated forms, [Cu(quin)2(pipe)2]∙CH3CN (8) and [Cu(quin)2(pipe)2]∙CH3CH2CN (9). Interestingly, only the piperidine system has experienced a reduction of copper(II). The involvement of amine in the reduction was undoubtedly confirmed by identification of a polycyclic piperidine compound 10, 6,13-di(piperidin-1-yl)dodecahydro-2H,6H-7,14-methanodipyrido[1,2-a:1',2'-e][1,5]diazocine.

From cyclic amines and acetonitrile to amidine zinc(ii) complexes.

A seemingly simple combination of [Zn(quin)2(H2O)] (quin- = quinaldinate) and a selected secondary cyclic amine, piperidine (pipe), pyrrolidine (pyro) or morpholine (morph), afforded in acetonitrile a number of products: anionic homoleptic quinaldinate, neutral heteroleptic quinaldinate/amine and quinaldinate/amidine complexes. The piperidine and pyrrolidine systems underwent reaction with acetonitrile to give amidines. The in situ formed piperidinoacetamidine (pipeam) or pyrrolidinoacetamidine (pyroam) coordinated to zinc(ii). Reactions with piperidine led to trans-[Zn(quin)2(pipe)2]·2CH3CN (1), [Zn(quin)2(pipe)]·cis-[Zn(quin)2(pipe)2] (2), pipeH[Zn(quin)3]·CH3CN (3), [Zn(quin)2(pipeam)]·CH3CN (4a), [Zn(quin)2(pipeam)]·2CHCl3 (4b), pipeamH[Zn(quin)3] (5) and pipeamH[Zn(quin)2(CH3COO)]·acetamide (6) (pipeH+ and pipeamH+ denote protonated amine or amidine). By analogy, [Zn(quin)2(pyro)2] (7), pyroH[Zn(quin)3]·CH3CN (8), pyroH[Zn(quin)2Cl] (9), [Zn(quin)2(pyroam)]·CH3CN·0.5pyroam·0.5H2O (10a), [Zn(quin)2(pyroam)]·2CHCl3 (10b), [Zn(quin)2(pyroam)]·CH2Cl2 (10c) and pyroamH[Zn(quin)3] (11) were obtained in the pyrrolidine reactions. The morpholine system allowed isolation of only two novel products, trans-[Zn(quin)2(morph)2] (12) and morphH[Zn(quin)3]·CH3CN (13). Importantly, no amidine could be isolated. Instead, in autoclaves at 105 °C morpholine degraded to ammonia, as confirmed by mass spectrometry of the gas phase. pyroamH[Zn(quin)3] exists in two polymorphs which differ in the binding modes of quinaldinate ligands. In 11triclinic, the metal ion of [Zn(quin)3]- features a five-coordinate environment, whereas that in 11monoclinic is surrounded by six donors. Stabilities of the [Zn(quin)3]- isomers were assessed with DFT calculations. The one with a six-coordinate zinc(ii) ion was found to be more stable than its five-coordinate counterpart. Favorable intermolecular interactions in the solid state stabilize both and reduce the energy difference between them. The calculations show the conversion of the five-coordinate [Zn(quin)3]- into its coordinatively saturated isomer to be an almost barrierless process.