8-Hydroxyquinoline, role

Further transformation included additional hydroxylation steps leading to 2,6-dihydroxyquinoline and a trihydroxyquinoline (probably 2,5,6-trihydroxyquinoline). Shukla [322], working with Pseudomonas sp. identified an alternate pathway, involving additional metabolites, besides the 2-hydroxyquinoline and 8-hydroxycoumarin. These were 2,8-dihydroxyquinoline and 2,3-dihydroxyphenylpropionic acid. Quinoline-adapted cells were also able to transform 2-hydroxyquinoline and 8-hydroxycoumarin without a lag phase, providing additional support for their intermediate role as intermediates in the metabolism of quinoline. 

The chemistry used to prepare the antischistosomal hydroxyquinolines provided the initial entry to this series. Thus, addition-elimination of aminopicoline (38-1) to EMME (38-2) gives the corresponding enamino ester (38-3). Thermal cyclization of that intermediate leads to the hydroxyquinoline (38-4). Reaction of the ambident anion from that compound leads to alkylation via the keto tautomer and thus the formation of the Al-alkylated derivative (38-5). Saponification of the ester then gives nalidixic acid (38-6) [44]. It has incidentally been shown that the presence of the strong Michael acceptor function in this series plays a little role in the mechanism of action in these compounds. 

The work described here supports the view that the chemical combination of metal ions with organic molecules leads to coordination complexes and polymers with enhanced stability with respect to weight loss, thermal degradation, or oxidation. Bis(8-hydroxyquinoline) derivatives were used to prepare a series of coordination polymers containing first-row transition metals, and the thermal stabilities of the polymers were evaluated. The influence of the structure of the organic molecule and the role of the metal are discussed. 

Proton transfer dynamics of photoacids to the solvent have thus, being reversible in nature, been modelled using the Debye-von Smoluchowski equation for diffusion-assisted reaction dynamics in a large body of experimental work on HPTS [84—87] and naphthols [88-92], with additional studies on the temperature dependence [93-98], and the pressure dependence [99-101], as well as the effects of special media such as reverse micelles [102] or chiral environments [103]. Moreover, results modelled with the Debye-von Smoluchowski approach have also been reported for proton acceptors triggered by optical excitation (photobases) [104, 105], and for molecular compounds with both photoacid and photobase functionalities, such as lO-hydroxycamptothecin [106] and coumarin 4 [107]. It can be expected that proton diffusion also plays a role in hydroxyquinoline compounds [108-112]. Finally, proton diffusion has been suggested in the long time dynamics of green fluorescent protein [113], where the chromophore functions as a photoacid [23,114], with an initial proton release on a 3-20 ps time scale [115,116]. 

The antimicrobial activity of chelate formers bases partly on their ability to compete for the complexion of metal cations necessary for a functional cell metabolism. However, membrane-activity of the compounds also plays a role. Antimicrobial agents which form chelates include besides the already mentioned azole fungicides 2-mercaptopyridine-N-oxide (pyrithione) [II, 13.1.3.] (Cooney and Felix, 1972 Chandler and Segel, 1978 Khattar et al., 1988), 8-hydroxyquinoline (oxine) [II, 13.3.](Albert et al, 1947 Albert, 1968), and dithiocarbamates [II, 11.11.], e.g. zineb, thiram (Ludwig and Thorn, 1960). 

Solvent extraction of metal ions plays an important role in hydrometallurgy. Further development of solvent extraction is constrained by the limited number of commercially available extractants which include di(2-ethylhexyl)phosphoric acid (D2EHPA), bis(2,2,4-trimethylpentyl)phosphinic acid (Cyanex 272 ), trioctyl-phosphine oxide (TOPO), tri- -butylphosphate (TBP), some hydroxy oximes (extractants in the LIX or Acorga series) and derivatives of 8-hydroxyquinoline (extractants in the Kelex and LIX-26 series). 

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