Theophylline silver

These observations contrast with those recorded by Davoll and Lythgoe,149 who obtained two isomeric desoxyribosides and only one desoxyglucoside by condensation of the appropriate acetohalogenosugar with theophylline silver. 

The methylxanthines vary in their ability to form certain metal complexes. For example, theophylline will complex with both copper and silver whereas caffeine will not.16 The interpretation of this is that the metal ion forms a pentacyclic complex involving the phenolic 0 at C-6 and N at 7.18... 

K. B. Sloan, S. A. Koch, K. G. Silver, Mannich Base Derivatives of Theophylline and 5-Fluorouracil Syntheses, Properties and Topical Delivery Characteristics , Int. J. Pharm. 1984, 21, 251 - 264. 

Because of the great interest in the naturally occurring nucleosides, studies of the synthesis of D-ribosides of purines and pyrimidines have been numerous. The first attempt in this direction was made by Levene and Sobotka146 who condensed the silver salt of theophylline with tri-acetyl- 8-D-ribopyranosyl bromide to obtain what was probably triacetyl-7- 8-D-ribopyranosyl theophylline (LXXVI). Subsequently Hilbert and Rist94 condensed 2,4-diethoxypyrimidine (LXXVII) with triacetyl-0-D-ribopyranosyl bromide (LXXVIII) to form ethyl bromide and 1-triacetyl-D-ribopyranosyl-4-ethoxyuracil (LXXX), which, on deacetylation with hydrogen chloride, gave 1-D-ribopyranosyluracil (LXXIX), an isomer of... 

Direct condensation of 2,3,5-tri-0-benzoyI-/3-D-ribofuranosyl bromide with adenine in acetonitrile at 50 °C leads after deblocking to the 3-/3-D-ribofuranosyladenine (132) (B-68MI40901). Metal derivatives of purines tend to produce 7- or 9-glycosyl derivatives thus the silver salt of 2,8-dichloroadenine with 2,3,5-tri-O-acetylribofuranosyl chloride produces the 9-/3-D-ribofuranosyl derivative (133) (48JCS967, 48JCS1685). However similar reactions with theobromine produce O-glycosides and with theophylline N-7 derivatives (34JCS1639). 

Theophylline-imprinted polymers prepared with MAA and EDMA were utilized for SPR sensors, in which the particles were immobilized on the silver film on the SPR sensor chip by evaporation from acetonitrile-acetic acid (99 1 v/v) containing the particles [20]. The detection limit was reported to be 0.4 mg/mL of theophylline in aqueous solution. 

Silver fluoride in pyridine is frequently used in the dehydrohalogenation of 5 -deoxy-5 -iodo-nucleosides for example, the theophylline and uracil nucleosides (383) and (384) respectively, were prepared in this way (see Scheme 89), whereas 3, 5 -dideoxy-3, 5 -di-iodothymidine gave the diene (236) when treated with silver fluoride in pyridine. However, 9-(2,5-dideoxy-j8-D- /ycero-pent-4-enofuranosyl)adenine (385) was best prepared by the action of DBU on 3 -0-acetyl-5 -bromo-2, 5 -dideoxyadenosine. In a synthesis of the 2, 3 -unsaturated... 

Theophylline also gives a silver salt quantitatively. It is only weakly acidic in water (pK = 8.60—see above aminophylline). In the presence of silver nitrate, it gives a silver monosalt, which precipitates ... 

In the list of the above-mentioned compounds, some of them form silver salts completely only in the presence of ammonia. This is the case for thiourea and also theophylline. The precipitation of thiourea by silver ions might be the result of the following two reactions ... 

The titration is a back titration according to Charpentier-Volhard s method after filtration of silver sulfide as well as acidification of fhe solution. Theophylline gives a silver theophillinate precipifafe only fofally in ammonia and after healing. Silver theophillinate does nol form in diluled acid medium, and ils precipilalion is incomplete in pure water. 

Other derivatives that are not ureides may, however, also be subject to this reaction. This is the case, for example, of theophylline, which is endowed with a weak acidic character due to its mobile hydrogen brought by the nitrogen in position 7. Theophylline s pK value is 8.6. To perform the titration, an excess of silver nitrate is added and the titration is carried out by sodium hydroxide. The indicator is bromothymol blue. 

Theophylline behaves analytically like theobromine. It can be quantitatively methylated to caffeine by the method of Self and Rankin given above and it forms an insoluble silver compound. However, sodium acetate is sometimes present and will interfere with the silver determination unless the acetic acid is volatilised with excess of standard sulphuric acid. 

Precipitation of theophylline as the silver compound, which is filtered off, is a useful method particularly for tablet formulations ... 

The results by this method are slightly more erratic than the longer gravimetric method since 0-1 ml of 0-1N silver nitrate is equivalent to 0-72 per cent of theophylline when 0 25 g is taken for assay. 

---