No abstract

New capsule-shaped hosts “cavitand-linked porphyrin” metal complexes (Mcp: M = H2, Ni, Zn, and Pd) have been synthesized to mimic the substrate binding functions of metalloenzymes such as cytochrome P-450cam. Crystal structures of cavitand 1·MeOH·CHCl3, [Zntpp(MeOH)], [Nicp]·MeOH·2CHCl3·3H2O, [Zncp(MeOH)]·2CHCl3·3H2O, and [Pdcp]·MeOH·2CHCl3·3H2O have been determined. One methanol molecule, originating from crystallization solvent is encapsulated in each host cavity, and coordinates to Zn in Zncp but not in Ni- and Pdcp. Encapsulation of various small hydrocarbon molecules in CDCl3 solutions of Mcps have been evaluated by determining binding constants and thermodynamic parameters obtained from 1H NMR titrations. All Mcps encapsulate hydrocarbons smaller than propane under atmospheric pressure. The guest size selectivity is primarily influenced by cavity size, and partly by metal insertion. The metal ion radius does not affect guest size selectivity. Encapsulation of coordinating guest molecules (MeOH, EtOH, MeCN, and H2O) in Mcps has also been investigated. Only Zncp favors coordination of non-hydrocarbon guests such as MeOH. We concluded that accommodation of different size guests by Mcps depends upon guest sizes and coordination of functional groups depends upon both the identity of the porphyrin’s metal ion and guest sizes.

Phenytoin (PHT), 5,5-diphenyl-2,4-imidazolidinedione, has been widely used in the management of patients with epilepsy, generalized convulsion and partial seizure. 1,2 PHT has been well established to have non-linear "dose dependent" pharmacokinetic properties and a narrow therapeutic range of 10 -20 µg/ml in serum. 3,4 Moreover, because PHT is ~90% bound to plasma protein, mainly to albumin 5 , the unbound concentration has been shown to be a better predictor of the therapeutic response than the total concentration. An accurate determination of the unbound-PHT concentration in serum is thus essential for therapeutic drug monitoring.Several methods used up to now to determine the PHT level have been based on either chromatography or immunochemical techniques. Although both an enzyme-multiplied immunoassay or a fluorescence polarization immunoassay have been widely utilized by clinical laboratories because of their speed and simplicity, these methods are interfered with by the PHT metabolites, and consequently tend to overestimate the PHT levels. 6-8 Some high-performance liquid chromatographic (HPLC) methods with ultraviolet (UV) detection have also been developed to determine the PHT level in human serum. 9-11 However, these methods have a limited sensitivity and require a large amount of serum ( > = 2 ml) to determine the presence of unbound-PHT.We previously developed 3-bromomethyl-6,7-dimethoxy-1-methyl-2(1H )-quinoxalinone (Br-DMEQ) as a highly sensitive fluorescence derivatization reagent for carboxylic acids in HPLC. 12 The HPLC method with Br-DMEQ has been successfully used to determine biologically important fatty acids 13 , prostaglandins 14 and antitumor agents (5-fluorouracil and 5-fluoro-2′-deoxyuridine). 15 We found that Br-DMEQ also reacts with PHT and its metabolites, 5-(3-hydroxyphenyl)-5-phenylhydantoin (3HPPH) and 5-(4-hydroxyphenyl)-5-phenylhydantoin (4HPPH) (Chart 1), having imino hydrogen to produce the corresponding fluorescent derivatives, which are separable by reversed-phase HPLC. We therefore developed a method for the simultaneous determination of PHT and the metabolites in human serum. Drug-free serum spiked with PHT, 3HPPH and 4HPPH was employed as model samples to establish the most suitable conditions for a general ana- A highly sensitive fluorometric high-performance liquid chromatographic method was developed for the simultaneous determination of phenytoin and its major metabolites [5-(3-hydroxyphenyl)-5-phenylhydantoin and 5-(4-hydroxyphenyl)-5-phenylhydantoin]. After extracting these compounds and 5-(4-methylphenyl)-5-phenylhydantoin (MPPH) as an internal standard from serum (50 µl) with ethyl acetate, they were further converted into the corresponding fluorescent derivatives by a reaction with 3-bromomethyl-6,7-dimethoxy-1-methyl-2(1H )-quinoxalinone in the presence of potassium hydrogen carbonate and dibenzo-18-crown-6 in acetonitrile. The derivatives were separated by reversed-phase chromatography on a YMC-Pack ODS-A column with a mixture of acetonitrile-50 mM phosphate buf...

An accommodating host: A new capsule‐shaped host molecule, the cavitand–porphyrin shown, reversibly encapsulates single hydrocarbon molecules smaller than propane (see picture). With the exception of acetylene, the binding affinities are inversely correlated with the size of the guest hydrocarbons.

Ein gastfreundlicher Wirt: Ein neues, kapselförmiges Wirtmolekül, das gezeigte Cavitandporphyrin, schließt reversibel einzelne Kohlenwasserstoffmoleküle kleiner als Propan ein (siehe Bild). Mit Ausnahme von Acetylen korrelieren die Bindungsaffinitäten invers mit der Größe des Gast‐Kohlenwasserstoffs.