Mechanisms of hydrolysis of phenyl- and benzyl 4-nitrophenyl-sulfamate esters.

The kinetics of hydrolysis at medium acid strength (pH interval 2-5) of a series of phenylsulfamate esters 1 have been studied and they have been found to react by an associative S(N)2(S) mechanism with water acting as a nucleophile attacking at sulfur, cleaving the S-O bond with simultaneous formation of a new S-O bond to the oxygen of a water molecule leading to sulfamic acid and phenol as products. In neutral to moderate alkaline solution (pH ≥ ~ 6-9) a dissociative (E1cB) route is followed that involves i) ionization of the amino group followed by ii) unimolecular expulsion of the leaving group from the ionized ester to give N-sulfonylamine [HN=SO(2)] as an intermediate. In more alkaline solution further ionization of the conjugate base of the ester occurs to give a dianionic species which expels the aryloxide leaving group to yield the novel N-sulfonylamine anion [(-)N=SO(2)]; in a final step, rapid attack of hydroxide ion or a water molecule on it leads again to sulfamic acid.

Development of structure-taste relationships for thiazolyl-, benzothiazolyl-, and thiadiazolylsulfamates.

A total of 28 new five-membered aromatic ring thiazolyl-, benzothiazolyl-, and thiadiazolylsulfamates, as their sodium salts, have been synthesized and combined with 30 known similar heterocyclic sulfamates to create a database for the study of structure-activity (taste) relationships (SARs) in this heterocyclic subgroup, which is known to contain a somewhat disproportionate number of sweet compounds compared to other groups of tastants. A series of nine parameters (descriptors) to describe the properties of the sulfamate anions were calculated in Spartan Pro and HyperChem programs. These are the highest occupied molecular orbital (HOMO), lowest unoccupied molecular orbital (LUMO), length of the molecule, dipole moment, area, volume, E(solv), sigma (from the literature), and log P.

Structure-taste relationships for disubstituted phenylsulfamate tastants using classification and regression tree (CART) analysis.

Forty-two new disubstituted phenylsulfamates have been synthesized, and 30 of these have been combined with 40 already available from earlier work to create a training database of 70 compounds. On the basis of panel taste data these were divided into three categories, N (nonsweet), N/S (nonsweet/sweet), and (S) sweet, and a "sweetness value" or weighting was also calculated for each compound. Using these 70 compounds as a training set and a series of nine predictors derived from Corey-Pauling-Koltun (CPK) models, calculated from the PC SPARTAN PRO program and Hammett sigma values taken from the literature, a classification and regression tree analysis (CART) was carried out leading to a regression tree that correctly classified 62 of the 70 compounds (89% overall correct classification).

Therapeutic facet joint interventions in chronic spinal pain: a systematic review of effectiveness and complications.

Background: Facet joint interventions are used frequently for managing chronic spinal pain. Evidence continues to accumulate supporting the clinical effectiveness of these procedures and defining potential complications.

Objective: To evaluate the effectiveness of three types of facet joint interventions (facet joint injections, medial branch blocks and facet joint neurotomy) in managing spinal pain.

Development of structure-taste relationships for monosubstituted phenylsulfamate sweeteners using classification and regression tree (CART) analysis.

Twenty monosubstituted phenylsulfamates (cyclamates) have been synthesized and have had their taste portfolios determined. These have been combined with 63 compounds already in the literature to give a database of 83 ortho, meta, and para compounds. A training set of 75 compounds was randomly selected leaving eight compounds as a test set.

Is the negative charge on RNHSO3-M+ an essential requirement for sulfamate sweetness?

Although many structure-taste studies have been carried out on sulfamate (cyclamate) sweeteners, there are still some unanswered questions-notably whether the sulfamate anion, -NHSO(3)(-), is essential for sweetness in this class of compounds. The literature is contradictory on this point; therefore, 14 sulfamate esters RNHSO(3)R', which contain the sulfamate moiety but without the negative charge, i.e.

Application of the U and gamma' models in binary sweet taste mixtures.

The U and Gamma' models of sensory interactions, successfully applied in olfaction for several years, are tested here using data from published studies on sweetness. The models are subsequently tested on new data obtained in studies of binary mixtures of four sodium sulfamates. The U model allows for the estimation of a global interaction, whereas the Gamma' model allows for the distinction between that which is due to an intrinsic interaction in the mixture itself and that which may be due to the power function exponents in the mixture.

Change in rate-determining step in an E1cB mechanism during aminolysis of sulfamate esters in acetonitrile.

The kinetics of the reactions of the nitrogen-sulfur(VI) esters 4-nitrophenyl N-methylsulfamate (NPMS) with a series of pyridines and a series of alicyclic amines and of 4-nitrophenyl N-benzylsulfamate (NPBS) with pyridines, alicyclic amines, and a series of quinuclidines have been investigated in acetonitrile (ACN) in the presence of excess amine at various temperatures. Pseudo-first-order rate constants (k(obsd)) have been obtained by monitoring the release of 4-nitrophenol/4-nitrophenoxide. From the slope of a plot of k(obsd) vs [amine], second-order rate constants (k'(2)) have been obtained for the pyridinolysis of NPMS, and a Brønsted plot of log k'(2) vs pK(a) of pyridine gave a straight line with beta = 0.

Epsilon-aminocaproic acid administration and stroke following coronary artery bypass graft surgery.

Background: Epsilon-aminocaproic acid is routinely used to reduce bleeding during cardiac surgery. Anecdotal reports of thrombotic complications have led to speculation regarding this drug's safety. We investigated the association between epsilon-aminocaproic acid administration and postoperative stroke.

Pharmacologic electroencephalographic suppression during cardiopulmonary bypass: a comparison of thiopental and isoflurane.

Unlabelled: In this study, we examined the cerebral oxygenation effects of two methods of pharmacologic burst suppression during cardiopulmonary bypass (CPB) in valvular heart surgery patients. Patients were randomly entered into one of three groups: control (n = 13, fentanyl and midazolam), control plus burst suppression doses of thiopental (n = 15), or control plus burst suppression doses of isoflurane (n = 16). Burst suppression (80% suppression) was accomplished in the thiopental and isoflurane groups 15 min before aortic cannulation and was maintained through aortic decannulation.

Predictors of cognitive decline after cardiac operation.

Despite major advances in cardiopulmonary bypass technology, surgical techniques, and anesthesia management, central nervous system complications remain a common problem after cardiopulmonary bypass. The etiology of neuropsychologic dysfunction after cardiopulmonary bypass remains unresolved and is probably multifactorial. Demographic predictors of cognitive decline include age and years of education; perioperative factors including number of cerebral emboli, temperature, mean arterial pressure, and jugular bulb oxygen saturation have varying predictive power.

The use of Doppler ultrasound to assist with sciatic nerve blocks.

Twenty consecutive patients requiring surgical procedures on a lower extremity received leg blocks using a modification of Labat's classic approach. A Doppler ultrasound pencil probe was used to identify the dominant arterial structure exiting the sciatic notch with the sciatic nerve. A block needle was inserted in the same orientation as the probe until paraesthesias were elicited; then 25 ml of local anesthetic was injected.

Structure-activity studies on sulfamate sweetners III: structure-taste relationships for heterosulfamates.

Eleven heterosulfamates have been synthesized, characterized, and evaluated for sweetness. Measurements of the molecular dimensions (x, y, z, and V) of these sulfamates and 22 others that had been reported previously and evaluated for sweetness have been made using Corey-Pauling-Koltun space-filling models. The first-order molecular connectivities (1Xv) of all the heterosulfamates have been calculated.

In vivo and in vitro studies with sulfamate sweeteners.

The sweet compounds 2-methyl- and 3-methylcyclohexyl- and 2-cyclohexenylsulfamates were fed to Wistar albino rats. The urine (and feces in the case of 2-cyclohexenylsulfamate) was examined for possible amine, ketone, and alcohol metabolites. The total percent of metabolites formed was low and the hexenyl compound gave a particularly small quantity of metabolite.

Structure-activity studies on sulfamate sweeteners II: semiquantitative structure-taste relationship for sulfamate (RNHSO-3) sweeteners-the role of R.

With the use of Corey-Pauling -Koltun space-filling models, measurements of defined parameters (x, y, and z) were made of the R groups in a large number of carbosulfamates, RNHSO-3. The correlation between sweet and nonsweet sulfamates and the defined parameters for R is good. As a test, 12 new carbosulfamates were synthesized and tasted.

Metabolic studies with nonnutritive sweeteners cyclooctylsulfamate and 4-methylcyclohexylsulfamate.

The nonnutritive sweeteners cyclooctylsulfamate and 4-methylcyclohexylsulfamate were fed separately to female Wistar albino rats, and the urine was examined for the possible metabolites cyclooctylamine, cyclooctanone, cyclooctanol, 4-methylcyclohexylamine, 4-methylcyclohexanone, and cis- and trans-4-methylcyclohexanols. The average percent conversions to cyclooctylamine, cyclooctanone, and cyclooctanol were 0.127, 0.

Drug treatment outcomes: is sex a factor?

A small random sample of data from the National CODAP system is used to determine and explain differences in treatment outcomes for men and women. Only small percentage differences, discerned through examination of categorical relationships between males and females, are found to exist. The authors conclude that this finding may suggest more positive outcomes for women in treatment since women experience more social prejudices than their male counterparts, and encounter greater barriers in completing treatment.

Effects of client characteristics on admission activity in United States federally funded drug treatment facilities.

Utilizing data from the National Institute on Drug Abuse's CODAP, this paper examines the effect of client characteristics and drug of abuse on certain admission activity variables. It generally sustains the hypotheses (1) that the demographic characteristics of clients (i.e.

The effect of prior treatment on treatment success.

The characteristics of clients discharged from federally funded treatment facilities reporting to CODAP are analyzed in terms of several variables. These are the reasons for discharge (treatment completed, transfer or referral, or treatment not completed), the primary drug of abuse at admission (opiates and nonopiates), and the number of prior treatment experiences. Two independent replications using data for two consecutive quarters produced the same results, finding that the likelihood of completing treatment decreases as the number of prior treatment experiences increases.

Metabolic studies of the nonnutritive sweeteners cyclopentylmethylsulfamate and cyclopentylsulfamate: determination of metabolites in rat urine.

The nonnutritive sweetener sodium cyclopentylmethyl-sulfamate was fed to Wistar albino rats. The urine was collected for 3 days, combined, and examined (GLC) for the metabolites cyclopentyl-methylamine and cyclopentylmethanol. The percent conversion to these metabolites was 0.

Metabolic studies with the nonnutritive sweetener cycloheptylsulfamate.

The nonnutritive sweetener cycloheptylsulfamate was administered orally to rabbits and rats. The urine of each species was separately collected for 3 days and examined for the metabolites cycloheptylamine, cycloheptanone, and cycloheptanol and for cycloheptylsulfamate. A previously tested GLC method was adapted for the determination of the metabolites.