Caffeine

The best known N-compound is caffeine (1,3,7-trimethylxanthine) because of its physiological effects (stimulation of the central nervous system, increased blood circulation and respiration). It is mildly bitter in taste (threshold value in water is 0.8-1.2 mmole/1), crystallizes with one molecule of water into silky, white needles, which melt at 236.5 °C and subhme without decomposition at 178 °C. The caffeine content of raw Arabica coffee is 0.9-1.4%, while in the Robusta variety, it is 1.5-2.6%. In contrast there are caffeine-free Coffea varieties. Santos, an Arabica coffee, is on the low side, while Robusta from Angola is at the top of the range given for caffeine content. Other purine alkaloids are theobromine (Arabica 36-40 mg/kg, Robusta 26-82 mg/kg) 

Caffeine forms, in part, a hydrophobic ti-complex with chlorogenic acid in a molar ratio of 1 1. In a coffee drink, 10% of the caffeine and about 6% of the chlorogenic acid present occur in this form. The caffeine level in beans is only slightly decreased during roasting. Caffeine obtained by the decaffeination process and s)uithetic caffeine are used by the pharmaceutical and soft drink industries. Synthetic caffeine is obtained by methyla-tion of xanthine which is synthesized from uric acid and formamide. 

Wanner and Kalberer (1966) studied the extensive degradation of caffeine (formula on page 224) in Cojfea arabica, and reported the release of C02 by excised older leaves after feeding -labeled alkaloid. 

No radioactivity was found in amino acids connected with C-1 metabolism, e.g., serine, citruUine, arginine, and methionine (Kalberer, 1964). Therefore, nothing definitive could be stated about the mechanism of the deme-thylating reaction however, it may be possible that the demethylation enzyme systems present in either tea (Thea sinensis) or coffee have been developed simultaneously as the tissue develops its capability of synthesizing the caffeine. The methylation of the purines (e.g., caffeine or theobromine from tea) makes them more hydrophilic and therefore makes their excretion easier (Ogutuga and Northcote, 1970). 

More Extensive Degradation of Alkaioids and Introduction of Their Cataboiites into Primary Metaboiic Pathways 

Two compounds that are used in some soft drinks formulations for specific purposes are caffeine, used in a range of beverages including colas for its stimulant properties, and quinine, used for its bitter taste. Traditional techniques for the analysis of these two compounds have often involved their extraction from aqueous solution into an organic solvent and then quantification by one of a range of methods. 

Over the last 5-10 years, there has been a rapid growth in drinks with certain associated attributes. As highlighted earlier, Red Bull has been a great success based on its energy and stimulant properties. However, there have been a range of other drinks which have focused on different aspects of health, and these often contain green tea extracts, soy extracts and/or extracts of herbs. 

Three spectrophotometric procedures are given in the AOAC compendium of methods (960.22, 962.13 and 967.11) for the analysis of caffeine, all of which have an extraction stage followed by a quantification procedure. There is also an HPLC method, discussed earlier, which was designed to measure saccharin, benzoic acid and caffeine at the same time (AOAC, 978.08). Again, the HPLC method, EN 12856 1999 (Anon, 1999a), can be used for the analysis of caffeine, but this analyte was not included in the collaborative study. 

In Pearson s Analysis of Foods two methods are quoted for the analysis of caffeine. The fust is a simple solvent extraction followed by quantification by ultraviolet absorbance at 273 nm (Egan et al., 1990d) and the other is a GLC method. 

Saxitoxin is an extremely toxic substance. It binds to sodium channels and the blocks nerve membrane. In humans, ingestion of this compound can produce tingling and burning in the lip, tongue, face, and the whole body within an hour. This is followed by numbness, muscular incoordination, confusion, headache, and respiratory failure. Death may occur within 12 hours. 

Intravenous administration of 1 mL of 1 2000 solution of prostigmine methylsulfate has been reported to be effective against saxitoxin poisoning (Hodgson et al. 1988). 

Pilocarpine is a tropane alkaloid. Toxic symptoms are characterized by muscarinic effects. Toxic effects include hypersecretion of saliva, sweat, and tears contraction of the pupils of the eyes and gastric pain accompanied with nausea, vomiting, and diarrhea. Other symptoms are excitability, twitching, and lowering of blood pressure. High doses may lead to death due to respiratory failure. A lethal dose in humans is estimated within the range of 150-200 mg. 

Synonyms 3,7-dihydro-l,3,7-trimethyl-l/7-purine-2,6-dione 1,3,7- trimethylxan thine 1,3,7-trimethyl-2,6-dioxopurine methyl-theobromine guaranine theine 

Synonyms 3 -ethyldihydro-4-(( 1 -methyl 1// -imidazol-5-yl)methyl)-2(377)-furanone al-mocarpine 

While experimental resistance to artemisinin had been induced earlier, blood samples from Cambodia, Senegal and French Guiana provided in 2005 the first hints on drug-resistant Plasmodium falciparum isolates in the field. [483] The first clinical cases were reported in 2008 from PaUin and other provinces in western Cambodia [484], and in 2012, resistant strains were also found in neighbouring Thailand. [485] In these coimtries, artemisinin and its derivatives had been frequently used as mono-therapy and in an imcontroUed fashion. While there is an enormous effort under way to elucidate the mechanisms of resistance development, the WHO urges to only apply artemisinin-based combination therapy (ACT) for the treatment of malaria in order to secure and maintain the efficacy of our most recent - and at the same time oldest - weapon in the combat of this devastating disease for as long as possible. [486] 

coffee is along with crude oil, natural gas, copper, silver, gold, sugar, cotton, corn, and wheat one of the world s largest trading commodities - worth more than 12 billion dollars in trade every year - and the 2nd most consumed beverage worldwide after water. Most of the world s coffee crop is produced in Southern and Central America, Asia and Africa. The United States is the biggest importer, while Finland is the nation that consumes the most per capita. 

The popularity of coffee is certainly attributable to its caffeine content. The alkaloid caffeine acts mildly euphorigenic, stimulating or relaxing, devoid of leading to any physical dependency, not even to a compensatory depressive phase or state of exhaustion. [487] 

In 1554, the first coffee-house was opened in Constantinople (the present-day Istanbul). In the second half of the 17th century, in the wake of the expansion and fall of the Ottoman Empire, coffee houses spread all across Europe, to Vienna, Venice, Paris, Marseille, London, Hamburg and to other places (Fig. 5.191). 

At around the same time, the Dutch brought the first coffee plants to Java. From the first half of the 18th century, cultivation of coffee is also traceable in the West Indies, in Ecuador, Venezuela and Brazil. [488] 

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C8H10N4O2. An alkaloid occurring in tea, coffee and guarana, from which it may be prepared by extraction, It is also manufactured by the methylation of theobromine and by the condensation of cyanoacetic acid with urea. Crystallizes with H2O or anhydrous from organic solvents. M.p. (anhydrous) 235"C, sublimes at 176 C. Odourless, and with a very bitter taste. Caffeine acts as a stimulant and diuretic, and is a constituent of cola drinks, tea and coffee. 

C7H9N402- M.p. 337 C, an alkaloid obtained from cacao seeds or prepared synthetically. Constitutionally it is similar to caffeine, and is also a weak base. It is usually administered as the sodium compound combined with either sodium ethanoate or sodium salicylate, and is employed almost entirely as a diuretic. Physiologically theobromine resembles caffeine, but its effect on the central nervous system is less, while its action on the kidneys, is more pronounced. 

C7HgN402. Occurs to a small extent in tea, but is chiefly prepared synthetically. Like caffeine, it is a very weak base which forms water-soluble compounds with alkalis. It has a similar pharmacological mechanism to that of caffeine and is used, in combination with ethy-lenediamine. as a diuretic and a bron-chodilator. 

XXVI, 2nd 1965 3794-4187 Four cyclic nitrogens, 321 Xanthine, 447. Caffeine, 461. Uric acid, 613. 

The nucleophilicity of the nitrogen atom survives in many different functional groups, although its basicity may be lost. Reactions of non-basic, but nucleophilic urea nitrogens provide, for example, an easy entry to sleeping-pills (barbiturates) as well as to stimulants (caffeine). The nitrogen atoms of imidazoles and indole anions are also nucleophilic and the NH protons can be easily substituted. 

Pyrimidines and purines occur naturally in substances other than nucleic acids Coffee for example is a familiar source of caffeine Tea contains both caffeine and theobromine... 

Classify caffeine and theobromine according to whether each is... 

Caffeine and theobromine are both purines Caffeine lacks H—N—C=0 units so cannot enobze Two consitutionally isomenc enols are possible for theobromine... 

This publication provides several examples of the use of solid-phase extractions for separating analytes from their matrices. Some of the examples included are caffeine from coffee, polyaromatic hydrocarbons from water, parabens from cosmetics, chlorinated pesticides from water, and steroids from hydrocortisone creams. Extracted analytes maybe determined quantitatively by gas (GC) or liquid chromatography (LG). 

Yang, M. J. Orton, M. L. Pawliszyn, J. Quantitative Determination of Caffeine in Beverages Using a Combined SPME-GC/MS Method, /. Chem. Educ. 1997, 74,... 

Caffeine is extracted from beverages by a solid-phase microextraction using an uncoated fused silica fiber. The fiber is suspended in the sample for 5 min and the sample stirred to assist the mass transfer of analyte to the fiber. Immediately after removing the fiber from the sample it is transferred to the gas chromatograph s injection port where the analyte is thermally desorbed. Quantitation is accomplished by using a C3 caffeine solution as an internal standard. 

Many pharmaceutical compounds are weak acids or bases that can be analyzed by an aqueous or nonaqueous acid-base titration examples include salicylic acid, phenobarbital, caffeine, and sulfanilamide. Amino acids and proteins can be analyzed in glacial acetic acid, using HCIO4 as the titrant. For example, a procedure for determining the amount of nutritionally available protein has been developed that is based on an acid-base titration of lysine residues. ... 

Procedures for determining the concentrations of caffeine, benzoic acid and aspartame in soda by these three methods are provided. In the example provided in this paper, the concentrations of caffeine and benzoic acid in Mello Yellow are determined spectrophotometrically. 

The analysis of APC tablets (a mixture of aspirin, phenacetin, and caffeine) has been a common undergraduate laboratory experiment. This experiment describes modifications to the standard analysis for APC tablets in which paracetamol (also known as acetaminophen) replaces phenacetin. 

Examples of the application of HPLC to the analysis of (a) acetaminophen, salicylic acid, and caffeine (b) chlorinated pesticides (c) tricyclic antidepressants and (d) peptides. (Chromatograms courtesy of Alltech Associates, Inc. Deerfield, IL). 

Caffeine in coffee, tea, and soda is determined by a solid-phase microextraction using an uncoated silica fiber, followed by a GC analysis using a capillary SPB-5 column with an MS detector. Standard solutions are spiked with G3 caffeine as an internal standard. 

The concentrations of benzoic acid, aspartame, caffeine, and saccharin in a variety of beverages are determined in this experiment. A Gig column and a mobile phase of 80% v/v acetic acid (pH = 4.2) and 20% v/v methanol are used to effect the separation. A UV detector set to 254 nm is used to measure the eluent s absorbance. The ability to adjust retention times by changing the mobile phase s pH is also explored. 

The concentration of caffeine in a typical serving of coffee and soda is determined in this experiment. Separations are achieved using a Gjg column with a mobile phase of 30% v/v methanol in water, with UV detection at a wavelength of 254 nm. 

This experiment focuses on developing an HPLG separation capable of distinguishing acetylsalicylic acid, paracetamol, salicylamide, caffeine, and phenacetin. A Gjg column and UV detection are used to obtain chromatograms. Solvent parameters used to optimize the separation include the pH of the buffered aqueous mobile phase, the %v/v methanol added to the aqueous mobile phase, and the use of tetrabutylammonium phosphate as an ion-pairing reagent. 

Conte, E. D. Barry, E. E. Rubinstein, H. Determination of Caffeine in Beverages by Capillary Zone Electrophoresis, ... 

Caffeine in tea and coffee is determined by CZE using nicotine as an internal standard. The buffer solution is 50 mM sodium borate adjusted to pH 8.5 with H3PO4. A UV detector set to 214 nm is used to record the electropherograms. 

Caffeine, benzoic acid, and aspartame in soft drinks are analyzed by three methods. Using several methods to analyze the same sample provides students with the opportunity to compare results with respect to accuracy, volume of sample required, ease of performance, sample throughput, and detection limit. 

Students determine the concentrations of caffeine, acetaminophen, acetylsalicylic acid, and salicylic acid in several analgesic preparations using both CZE (70 mM borate buffer solution, UV detection at 210 nm) and HPLC (C18 column with 3% v/v acetic acid mixed with methanol as a mobile phase, UV detection at 254 nm). 

Haddad and associates report the following capacity factors for the reverse-phase separation of salicylamide (k i) and caffeine... 

Suppose that you are to separate a mixture of benzoic acid, aspartame, and caffeine in a diet soda. The following information is available to you. 

The amount of caffeine in an analgesic tablet was determined by HPLC using a normal calibration curve. Standard solutions of caffeine were prepared and analyzed using a lO-pL fixed-volume injection loop. Results for the standards are summarized in the following table. 

Diet soft drinks contain appreciable quantities of aspartame, benzoic acid, and caffeine. What is the expected order of elution for these compounds in a capillary zone electrophoresis separation using a pH 9.4 buffer solution, given that aspartame has pJC values of 2.964 and 7.37, benzoic acid s pfQ is 4.2, and the pfQ for caffeine is less than 0. 

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