Quinine interactions

One aspect of asymmetric catalysis has become clear. Every part of the molecule seems to fulfill a role in the process, just as in enzymic catalysis. Whereas many of us have been used to simple acid or base catalysis, in which protonation or proton abstraction is the key step, bifunctional or even multifunctional catalysis is the rule in the processes discussed in this chapter.Thus it is not only the increase in nucleophilicity of the nucleophile by the quinine base (see Figures 6 and 19), nor only the increase in the electrophilicity of the electrophile caused by hydrogen bonding to the secondary alcohol function of the quinine, but also the many steric (i.e., van der Waals) interactions between the quinoline and quinuclidine portions of the molecule that exert the overall powerful guidance needed to effect high stereoselection. Important charge-transfer interactions between the quinoline portion of the molecule and aromatic substrates cannot be excluded. 

FIGURE 1.10 Comparison of enantiomer separations of DNB-Leu on quinine (QN) based and 0-9-(terf-butylcarbamoyl)quinine (tBuCQN) based CSPs. 1, ionic interaction 2, jt-7T-interaction 3, hydrogen bonding 4, steric interaction. Experimental conditions Eluent, methanol-0.1 M ammonium acetate (80 20 v/v) (pHa = 6.0) flowrate, 1 mLmin temperature, 25°C column dimension, 150 x 4 mm ID detection, UV 250 nm. Selector loadings, 0.37 and 0.30 mmol g l for QN- and tBuCQN-based CSPs, respectively. (Reproduced from A. Mandl et ah, J. Chromatogr. A, 858 1 (1999). With permission.)... 

It is also worthwhile to outline at this place the immobilization procedure that was used for the preparation of type I CSPs A bifunctional linker with a terminal isocyanate on one side and a triethoxysilyl group on the other end (3-isocyanatopropyl triethoxysilane) was reacted with the native cinchona alkaloids quinine and quinidine and subsequently the resultant carbamate derivative in a second step with silica [30], Remaining silanols have been capped with silane reagents, yet, are less detrimental for acidic solutes because of the repulsive nature of such electrostatic interactions. CSPs prepared in such a way lack the hydrophobic basic layer of the thiol-silica-based CSPs mentioned earlier, which may be advantageous for the separation of certain analytes. 

Another issue is validated by the presented X-ray structures This is related to the pseudoenantiomeric character of the tert-butylcarbamates of quinine and quinidine (Figure 1.19a,b). Except for the vinyl on the backside of the quinuclidine ring, both the complexes that are actually diastereomeric to each other actually look like mirror images with regard to conformations and intermolecular interactions as well so that the pseudoenantiomeric experimental chromatographic behavior for DNB-Leu can be rationalized also on the basis of their X-ray crystal structures. 

New brush-type phases (donor-acceptor interactions) are appearing all the time. " Examples are stationary phases comprising quinine derivatives and trichloro-dicyanophenyl-L-a-amino acids as chiral selectors. Quinine carbamates, which are suitable for the separation of acidic molecules through an ionic interaction with the basic quinine group, are also commonly used but in general they are classified with the anion-exchange type of chiral selectors (see further) because of their interaction mechanism, even though r-donor, r-acceptor properties occur. (Some separations on Pirkle-type CSPs are shown in Table 2.)... 

Several sensory modalities can be involved in complex interactions involving at least three cues rats learnt better to associate the bitter taste of quinine in water with a context such as a black or white box if a pyrazine was also present (the specific compound used was 2-methoxy-3-isobutyl pyrazine) (Kaye etal, 1989). It is said the odor potentiates learning the connection between taste cue and context. ... 

Drugs that may interact with rifabutin include the following Anticoagulants, azole antifungal agents, benzodiazepines, beta blockers, buspirone, corticosteroids, cyclosporine, delavirdine, doxycycline, hydantoins, indinavir, rifamycins, losartan, macrolide antibiotics, methadone, morphine, nelfinavir, quinine, quinidine, theophylline, aminophylline, tricyclic antidepressants, and zolpidem. 

Zhao, X. J. and Ishizaki, T. (1997) Metabolic interactions of selected antimalar-ial and non-antimalarial drugs with the major pathway (3-hydroxylation) of quinine in human liver microsomes. Br. J. Clin. Pharmacol. 44, 505-511. 

B Fritzsch, RHH Neubert, G Dongowski, L Heinevetter. Interactions between food components and drugs—part 8 effect of pectins and bile acid preparations forming stable mixed micelles on transport of quinine in vitro. Pharmazie 55 59-61, 2000. 

T Pancreatic insulin release Metformin Peripheral insulin sensitivity hepatic glucose output/production i intestinal glucose absorption Dose Ist-line (naive pts), 1.25/250 mg PO daily-bid 2nd-line, 2.5/500 mg or 5/500 mg bid (max 20/2000 mg) take w/ meals, slowly T dose hold before 48 h after ionic contrast media Caution [C, -] Contra SCr >1.4 mg/dL in females or >1.5 mg/dL in males hypoxemic conditions (sepsis, recent MI) alcoholism metabolic acidosis liver Dz Disp Tabs SE HA, hypoglycemia, lactic acidosis, anorexia, N/V, rash Additional Interactions T Effects W/ amiloride, ciprofloxacin cimetidine, digoxin, miconazole, morphine, nifedipine, procainamide, quinidine, quinine, ranitidine, triamterene,... 

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