Extraction of methyl xanthines and their UHPLC–DAD determination in consumable beverages used in Eastern province of Saudi Arabia

Coffee and tea are the most widely consumed beverages worldwide. However, the consumer may be unaware of the exact amount of methyl xanthine (MX, i.e. caffeine [C], theobromine [TB] and theophylline [TH]) consumed, as most of the products do not list the proper amounts. This may lead to serious risks including cardiovascular, kidney and stimulant effects. The aim of the study was to determine the MX amount in ready-to-use beverages (coffee and tea) collected from various outlets in the city of Al-Khobar, Saudi Arabia. Forty different samples of espresso, black coffee and red tea were collected. A fast, reliable and efficient UHPLC–DAD method was developed and validated for MX determination. Total lipids were extracted and fractionated in order to determine glycolipids, phospholipids and neutral lipids. The r² value for the method was 0.980–0.988 in a linearity range of 0.5–200 ppm. The range for MX (C [0.02–2.39 mg/ml], TB [0.00–0.10 mg/ml] and TH [0.00–0.004 mg/ml]) and total lipids was 1–5 g. The amount of glycolipids (3.1 g) was higher among the lipid fractions followed by phospholipids (1.8 g) and neutral lipids (0.25 g). In general, espresso beverages (20–30 ml) contained high amounts of MX whereas black coffee beverages contained high amount of lipids. Most of the beverages expressed C, TB, TH, lipids or their fractions; however, the product with high amounts of MX and lipids at the same time was espresso (brands Chemistry and Wogard). Although the MX and lipid levels in these beverages well below the allowed limits, care must still be taken, especially when using the beverages with high serving volumes (200–250 ml) or coffee prepared via the filter method i.e. black coffee, using a high temperature for a longer time.     

Salt effects in the aqueous alkaline hydrolysis of N-hydroxyphthalimide. Kinetic evidence for the ion-pair formation

The effects of the concentrations of LiCl, NaCl, KCl, CsCl, Na₂CO₃, BaCl₂, and Me₄NCl on the rates of reactions of hydroxide ion with ionized N-hydroxyphthalimide (NHP) at 30°C and in a H₂O–MeCN solvent containing 98%, v/v, H₂O reveal a nonlinear increase in observed rate constants with increase in salt concentrations. The observed rate constants are highly sensitive to the valence state of cations and almost insensitive to the valence state of anions of the salts. These observations are explained in terms of ion-pair formation between cations and NHP^?.     

Effects of mixed H2O‐CH3CN solvents on the rate of hydrazinolysis of N‐phenylphthalimide: Spectral and kinetic evidence for the occurrence of N‐aminophthalimide on the reaction path

Kinetic study on the cleavage of N‐phenylphthalimide (NPhPT) in the presence of 0.05 M NH₂NH₂ and mixed H₂O‐CH₃CN solvents reveals the occurrence of reaction scheme where A, B, C, C₁, An, E, and F represent NPhPT, o‐CO^?₂C₆H₄CONHC₆H₅, o‐CONHNH₂C₆H₄‐ CONHC₆H₅, N‐aminophthalimide, aniline, o‐CO^?₂C₆H₄CONHNH₂, and o‐CONHNH₂C₆H₄‐CONHNH₂, respectively. But, in the presence of either nonbuffered ?0.20 M NH₂NH₂ hydrazine buffer of pH ～7.30–8.26 with total buffer concentration ([Buf]_T) of >0.02 M, further conversion of F to 2,3‐dihydrophthalazine‐1,4‐dione (DHPD) has been detected depending upon the length of the reaction time (t), the values of [Buf]_T, and pH. It has been shown that the rate of conversion of C₁ to F is much faster than that of C to C₁ which is much faster than that of F to DHPD. The reaction step A → C involves general base (GB) catalysis, while step C → C₁ seems to involve specific base–general acid (GA) and GB‐GB catalysis. © 2005 Wiley Periodicals, Inc. Int J Chem Kinet 37: 147–161, 2005     

Synthesis and Characterization of Novel Monoazo N‐Ester‐1,8‐Naphthalimide Disperse Dyestuffs

Five novel monoazo disperse dyestuffs based on N‐ester‐1,8‐naphthalimide were synthesized. Acenaphthene was nitrated, then oxidized to 4‐nitro‐1,8‐naphthalic anhydride. 4‐Nitro‐1,8‐naphthalic anhydride was reacted with methyl and ethyl glycinate in alcoholic media, followed with reduction. 4‐Amino‐N‐methyl and ethyl glycinate‐1,8‐naphthalimide were obtained. These products were diazotized and coupled with appropriate aromatic amines to give bluish‐red or violet dyestuffs. All intermediates and dyestuffs were purified and characterized by ¹H‐NMR, FTIR, DSC, UV‐VIS and Elemental Analysis. Dispersion of dyestuffs was prepared in water and applied to polyester fabrics. The dyed fabrics showed that four of the synthesized dyestuffs were suitable for coloring polyester fibers, producing deep bluish red with very good build up properties.     

Effects of Nonionic and Mixed Cationic-Nonionic Micelles on the Rate of Alkaline Hydrolysis of 4-Nitrophthalimide

Pseudo-first-order rate constants (k_obs) for alkaline hydrolysis of 4-nitrophthalimide show a monotonic decrease with increase in [C₁₂E₂₃]_T (total concentration of Brij 35) at constant [CH₃CN] and [NaOH]. This micellar effect is explained in terms of a pseudophase micelle model. The rate of hydrolysis becomes too slow to monitor at [C₁₂E₂₃]_T≥0.03 M in the absence of cetyltrimethylammonium bromide (CTABr) and at [C₁₂E₂₃]_T≥0.04 M in the presence of 0.006–0.02 M CTABr at 0.01 M NaOH. The plots of k_obs versus [C₁₂E₂₃]_T show minima at 0.006 and 0.01 M CTABr, while such a minimum is not visible at 0.02 M CTABr.     

Facile synthesis of 3-substituted quinazoline-2,4-dione and 2,3-di-substituted quinazolinone derivatives

3-Substituted quinazoline-2,4(1H,3H)-dione and 2,3-di-substituted quinazolineone derivatives attract considerable interest due to their pharmacological properties. In this paper, we report the synthesis of N-substituted-3-nitrophthalimide derivatives II?CIII, the reactions of phthalimide III with amines, hydrazines, and amino acid derivatives to synthesise a small library of 3-substituted-5-nitroquinazoline-2,4(1H,3H)-diones IV?CXIV and 2,3-di-substituted-6-nitro-quinazolineones XVIII?CXIX.     

A new semiempirical kinetic method for the determination of ion exchange constants for counterions of cationic micelles: Study of the rate of pH‐independent hydrolysis of phthalimide as the kinetic probe

Pseudo‐first‐order rate constants (k_obs) for pH‐independent hydrolysis of phthalimide ( 1 ), obtained at a constant total concentration of cetyltrimethylammonium bromide and hydroxide ([CTABr]_T), 2.0 × 10^?4 M 1 , 0.02 M MOH (M⁺ = Li⁺, Na⁺ and K⁺) and various concentrations of inert salt MX (= LiCl, LiBr, NaCl, NaBr, KCl and KBr), follow a relationship derived from the pseudophase micellar (PM) model coupled with an empirical equation. This relationship gives empirical constants, F_X/S and K_{X /S}, with S representing anionic 1 . The magnitude of F_X/S is the measure of the fraction of micellized anionic 1 (S^?_M) transferred to the aqueous phase by the limiting concentration of X^?. The value of K_X/S is the measure of the ability of the counterions (X^?) to expel the reactive counterions (S^?) from the cationic micellar surface to the aqueous phase. The values of F_{X/ S} are ～ 1 for MBr (M⁺ = Li⁺, Na⁺ and K⁺) and in the range ? 0.7 to ? 0.5 for MCl (M⁺ = Na⁺ and K⁺) at 0.006, 0.010 and 0.016 M CTABr. For LiCl, the values of F_X/S become ～1 at 0.006 and 0.010 M CTABr and 0.8 at 0.016 M CTABr. The values of the empirical constants, F_X/S and K_X/S, have been used to determine the usual ion exchange constant (K^Cl_Br). The mean values of K^Cl_Br are 3.9 ± 0.5, 2.7 ± 0.1, and 2.6 ± 0.3 for LiX, NaX, and KX, respectively. These values of K^Cl_Br are comparable with those obtained directly by other physicochemical techniques. Thus, this new method for the determination of ion exchange constants for various counterions of cationic micelles may be considered as a reliable one. © 2010 Wiley Periodicals, Inc. Int J Chem Kinet 43: 9–20, 2011     

Kinetics and mechanism of tertiary amine‐catalyzed cleavage of N′‐morpholino‐N‐(2′‐methoxyphenyl)phthalamide: Kinetic evidence for the presence of a reactive intermediate on the reaction path

Pseudo‐first‐order rate constants (k_obs) for tertiary amine (DABCO and Me₃N) buffer‐catalyzed cyclization of N′‐morpholino‐N‐(2′‐methoxyphenyl)phthalamide ( 1 ) to N‐(2′‐methoxyphenyl)phthalimide ( 2 ) reveal saturation (nonlinear) plots of k_obs versus [Buf]_T (total tertiary amine buffer concentration) at a constant pH. Such plots at different pH have been attributed to the presence of a reactive intermediate (T^?) formed by tertiary amine buffer‐catalyzed intramolecular nucleophilic addition of the secondary amide nitrogen to the carbonyl carbon of the tertiary amide group of 1 . © 2010 Wiley Periodicals, Inc. Int J Chem Kinet 42: 263–272, 2010     

Structure–reactivity relationships and the rate–determining step in the reactions of methyl salicylate with primary amines

The aqueous cleavage of methyl salicylate has been studied in the buffer solutions of various primary mono- and di-amines as well as secondary amines at 30°C. Both ionized (MS^?) and nonionized (MSH) methyl salicylate are reactive toward primary mono- and di-amines. The second-order rate constants for the reactions of MS^? with primary mono- and di-amines of pK_a > 9.4 exhibit Bronsted plot of slope (β_nuc) of 0.82. This high value of β_nuc is attributed to an intramolecular proton transfer in a thermodynamically unfavorable direction in the rate-determining step in a stepwise process for the formation of monoanionic tetrahedral intermediate. However, a concerted process for the formation of a monoanionic tetrahedral intermediate in the reactions of MS^? with amine nucleophiles wherein expulsion of leaving group is a rate-determining step is not completely ruled out. The α-effect nitrogen nucleophiles hydroxylamine and hydrazine reveal, respectively, ca. 10⁴- and 10³-fold higher reactivity compared to other amine nucleophiles of comparable basicity. The value of β_nuc of 1.03 obtained for the reactions of primary monoamines with MSH is ascribed to the expulsion of leaving group as the rate-determining step. The significantly lower value of β_nuc of 0.60 obtained in the reactions of MSH with both monoprotonated and unprotonated diamines is explained in terms of possible occurrence of intramolecular general acid-base catalysis. Intramolecular general base catalysis is responsible for the enhanced nucleophilic reactivity of primary amines toward MS^?. Dimethylamine, piperidine, morpholine, and piperazine have no detectable nucleophilic reactivity toward MS^?.     

Rapid preparative isolation of erythrocentaurin from Enicostemma littorale by medium‐pressure liquid chromatography,its estimation by high‐pressure thin‐layer chromatography,and its α‐amylase inhibitory activity

Erythrocentaurin is a relatively simple natural product present among the members of Gentianaceae. A preparative method for the isolation of erythrocentaurin from the ethyl acetate fraction of Enicostemma littorale using medium‐pressure liquid chromatography has been reported. The method consisted of a simple step gradient from 10 to 20% ethyl acetate in n‐hexane. Using a 70 × 460 mm Si60 column, this method is capable of processing 20 g of material in <3 h (purity ≈ 97%). The recovery of erythrocentaurin was 87.77%. Estimation of erythrocentaurin in extracts and fractions based on high‐pressure thin‐layer chromatography was carried out on silica gel 60 F₂₅₄ plates with toluene/ethyl acetate/formic acid (80:18:2 v/v/v) as the mobile phase. The densitometric analysis was performed at 230 nm. A well‐separated compact band of erythrocentaurin appeared at R_f 0.54 ± 0.04. The analytical method showed good linearity in the concentration range of 200–1500 ng/band with a correlation coefficient of 0.99417. The limits of detection and quantification were found to be ≈60 and ≈180 ng/band, respectively. Erythrocentaurin exhibited a concentration‐dependent α‐amylase inhibition (IC₅₀ 1.67 ± 0.28 mg/mL). The outcome of the study should be considered for pharmacokinetic and biotransformation studies involving E. littorale.