ABSTRACT
Six aminoethyl and aminobutyl esters of ketorolac containing 1-methylpiperazine (MPE and MPB), N-acetylpiperazine (APE and APB) or morpholine (ME and MB), were synthesized and their hydrolysis kinetics were studied. The hydrolysis was studied at pH 1 to 9 (for MPE, APE and ME) and pH 1 to 8 (for MPB, APB and MB) in aqueous phosphate buffer (0.16 M) with ionic strength (0.5 M) at 37°C. Calculation of k(obs), construction of the pH-rate profiles and determination of the rate equations were performed using KaleidaGraph® 4.1. The hydrolysis displays pseudo-first order kinetics and the pH-rate profiles shows that the aminobutyl esters, MPE, APB and MB, are the most stable. The hydrolysis of the ethyl esters MPE, APE and ME, depending on the pH, is either fast and catalyzed by the hydroxide anion or slow and uncatalyzed for the diprotonated, monoprotonated and nonprotonated forms. The hydrolysis of the butyl esters showed a similar profile, albeit it was also catalyzed by hydronium cation. In addition, the hydroxide anion is 105 more effective in catalyzing the hydrolysis than the hydronium cation. The hydrolysis pattern of the aminoethyl esters is affected by the number and pKa of its basic nitrogen atoms. The monobasic APE and ME, show a similar hydrolysis pattern that is different than the dibasic MPE. The length of the side chain and the pKa of the basic nitrogen atoms in the aminoethyl moiety affect the mechanism of hydrolysis as the extent of protonation at a given pH is directly related to the pKa.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/chemistry , Cyclooxygenase Inhibitors/chemistry , Esters/chemistry , Ketorolac/analogs & derivatives , Prodrugs/chemistry , Anti-Inflammatory Agents, Non-Steroidal/chemical synthesis , Catalysis , Cyclooxygenase Inhibitors/chemical synthesis , Drug Stability , Esters/chemical synthesis , Hydrogen Bonding , Hydrogen-Ion Concentration , Hydrolysis , Hydroxides/chemistry , Ketorolac/chemistry , Kinetics , Models, Molecular , Molecular Structure , Morpholines/chemistry , Onium Compounds/chemistry , Piperazines/chemistry , Prodrugs/chemical synthesis , ProtonsABSTRACT
Water with high nitrate concentration (NO(3) (-)) is unfit for human consumption, especially when its concentration exceeded the threshold limit (50 mg/l) recommended by the health authorities such as the World Health Organization (WHO). In Jordan, there is a great concern for determination and monitoring organic and inorganic pollutants that may reach groundwater. Nitrate is highly mobile and present in domestic, agricultural and industrial waste in Jordan, and thus this study focused initially on nitrate as both a contaminant of concern and as an indicator of potential groundwater contamination. The present study determined the extent of nitrate contamination in groundwater in the study area and examined the likely sources of NO(3) (-). A total of 248 groundwater samples were collected from 16 wells in different sites of Al-Hashimiya area, Zerqa Governorate, Jordan, and investigated for NO(3) (-) concentrations. Moreover, measurements of temperature, electrical conductivity and pH were carried out in the field. Analysis was carried out according to the methods described by the American Public Health Association (APHA). Results showed that there was a dramatic increasing in NO(3) (-) concentrations from the year 2001 to 2006 for some selected wells in the present study. NO(3) (-) concentration in 2006 was ranged from 10 to 330 mg/l with an average of 77 mg/l. Overall, groundwater had elevated nitrate concentration with 92% of the samples containing more than 20 mg/l NO(3) (-), indicating the influence of human activities. This study has shown that there is a strong correlation between the nitrate concentration and the wastewater effluents as a source of pollution.
Subject(s)
Environmental Monitoring , Fresh Water/analysis , Nitrates/analysis , Water Pollutants, Chemical/analysis , Water Supply/analysis , Agriculture , Geography , Housing , Humans , Hydrogen-Ion Concentration , Industrial Waste , Jordan , Public Health , Risk Assessment , Time Factors , Water Supply/standardsABSTRACT
Epoxidations of alkyl-substituted alkenes, with hydrogen peroxide as the oxygen source, are catalyzed by CH(3)ReO(3) (MTO). The kinetics of 28 such reactions were studied in 1:1 CH(3)CN-H(2)O at pH 1 and in methanol. To accommodate the different requirements of these reactions, (1)H-NMR, spectrophotometric, and thermometric techniques were used to acquire kinetic data. High concentrations of hydrogen peroxide were used, so that diperoxorhenium complex CH(3)Re(O)(eta(2)-O(2))(2)(H(2)O), B, was the only predominant and reactive form of the catalyst. The reactions between B and the alkenes are about 1 order of magnitude more rapid in the semiaqueous solvent than in methanol. The various trends in reactivity are medium-independent. The rate constants for B with the aliphatic alkenes correlate closely with the number of alkyl groups on the olefinic carbons. The reactions become markedly slower when electron-attracting groups, such as halo, hydroxy, cyano, and carbonyl, are present. The rate constants for catalytic epoxidations with B and those reported for the stoichiometric reactions of dimethyldioxirane show very similar trends in reactivity. These findings suggest a concerted mechanism in which the electron-rich double bond of the alkene attacks a peroxidic oxygen of B. These data, combined with those reported for the epoxidation of styrene (a term intended to include related molecules with ring and/or aliphatic substituents) by B and by the monoperoxo derivative of MTO, suggest that all of the rhenium-catalyzed epoxidations occur by a common mechanism. The geometry of the system at the transition state can be inferred from these data, which suggest a spiro arrangement.
