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A number of low chlorine potential, soft N-chloramines containing nitrogen-chlorine bonds of different polarity were prepared. These novel N-chloramine systems were based on derivatization of 2-amino-2-methyl-1-propanol.
The kinetics and mechanisms of chlorine transfer from chloramine-T (CAT) to several amines are second order and independent of p-toluenesulfonamide concentration; thus, the reaction does not involve disproportionation of CAT to dichloramine-T. From the profile of pH versus rate, the following mechanisms were proposed: (1) reaction of the ionized species of CAT with the ionized amine (ionic mechanism) and (2) reaction of the un-ionized species of CAT with the un-ionized amine (nonionic mechanism). The second-order, pH-independent rate constants calculated for the ionic and nonionic mechanisms were 1.6 and 5 x 10(6) M-1 s-1, respectively. Although these two mechanisms are kinetically indistinguishable, the rate constant for the nonionic mechanism is of the same order of magnitude as those calculated for similar chlorination reactions involving nonionizable chloramines, such as N-chlorosuccinimide, N-chloroquinuclidine, and N-chloro-N-methylbenzenesulfonamide. The proposed mechanism for the chlorine exchange involves a molecule of water in a cyclic, six-membered transition state.
Chloramine-T (CAT) is commonly used in radiolabeling of bioactive molecules by halogenation. CAT is used to release radioactive elemental iodine by oxidation of its salts. Unfortunately, CAT is a strong oxidizing agent and can cause significant damage to peptides and proteins. This may lower the yield of the iodination reaction and may produce undesirable side products. Recently, it was found that the in situ formation of N-chlorosecondary amines, by the addition of secondary amines to CAT prior to exposure to the substrate, can reduce the oxidative damage caused by CAT. To simplify the method, we prepared penta-O-acetyl-N-chloro-N-methylglucamine (NCMGE) as a solid N-chlorosecondary amine. The chemical reactivity of NCMGE toward a model amino acid, 1-aminocyclohexane carboxylic acid, was compared with that of chloramine-T. In the presence of the model amino acid, CAT lost all its chlorine titer within 60 min while NCMGE retained 99% of its chlorine titer. NCMGE was compared to CAT for the iodination of l-tyrosine and leucine enkephalin. For both substrates, the NCMGE method produced larger or equal yields of the monoiodo and diiodo products and less decomposition. It is proposed that the method employing NCMGE to release diatomic iodine is more convenient and efficient for radiolabeling peptides and proteins than currently used methods.
Single myelinated nerve fibres of the frog, Rana esculenta, were voltage clamped in a fast-exchange chamber in the presence of 10 mM TEA to block potassium channels. After treatment with 0.6 mM chloramine-T for 1-4 min a sizeable INa component persisted even during a 14-s depolarizing impulse. Changing the perfusate to Ringer solution + 1 mM benzocaine resulted in a fast reduction (half time ca. 0.06 s) of the persistent INa, comparable to the rate of block of peak INa during a series of short impulses before chloramine-T. In the presence of 60 microM veratridine the peak INa was followed by a slow exponential (tau s) reincrease of inward current, Is, that did not appreciably inactivate. Application of 0.25 mM benzocaine during a 14-s depolarizing impulse caused Is to decrease exponentially with a large time constant, tau on of 4.3 s. Recovery on washout proceeded with tau off = 3.4s. Tau on was little dependent on benzocaine concentration and was 4.5 s on the average in 1 mM. Tau on in 25 microM was insignificantly (15%) larger than in 1 mM if tested on the same fibre. After equilibration in 25 microM, 0.25 mM and 1 microM, Is(t = 14s) was reduced to 0.69, 0.30, and 0.10, respectively, of the value without anaesthetic. Cooling by only 4-5 degrees C reduced Is and much increased tau s. tau on (1 mM benzocaine) increased almost in proportion to tau s. Tail currents during a series of pulses (1.1 s every 2.5 s) were reduced by 0.25 mM benzocaine clearly faster (tau on = 1.3 s) than Is during a long pulse of the same amplitude.(ABSTRACT TRUNCATED AT 250 WORDS)
A method is described for the enzymatic radioiodination of human follicle-stimulating hormone (hFSH) by a system consisting of lactoperoxidase, hydrogen peroxide and Na125I. It was compared with the Chloramine-T modified technique. A satisfactory specific activity of the labelled hormone was obtained with the enzymatic iodination with much greater immunoreactivity was stability than after Chloramine-T.
Granulocyte-derived chlorinated amines and bacterial formyl peptides are thought to enhance epithelial permeability. In the current study, gut permeability to [51Cr]ethylenediaminetetraacetic acid (EDTA) was monitored in response to luminal formyl-methionyl-leucyl-phenylalanine (fMLP) and histamine monochloramine and dichloramine. Responses were determined in rabbits during states of basal and elevated permeability. Luminal fMLP had minimal effects of gut permeability in control and injured states. Histamine monochloramine or dichloramine enhanced epithelial permeability under basal conditions; this effect was exaggerated by a pre-existing injury. Both histamine monochloramine and dichloramine retained full histamine agonist properties, and a combination of antioxidant and antihistamine therapy was required to block this increase in gut permeability. Whereas histamine chloramines caused a dose-dependent cytotoxicity in rat-cultured enterocytes, marked histological changes to the mucosa were not evident, nor were mucosal glutathione levels depleted. As histamine chloramines retain the histaminergic and oxidizing potential of their precursors, they represent a unique form of inflammatory mediator, although their highly reactive nature precludes in vivo confirmation of their formation.
The accumulation of polymorphonuclear leucocytes (PMN) may play an important role in liver injury by toxins and ischemia/reperfusion. Upon activation these cells generate hypochlorous acid (HOCl) and long-lived oxidants such as monochloramine (NH2Cl) and taurinechloramine (TauNHCl) which could contribute to organ injury when PMN accumulate in the liver. Therefore, the effects of HOCl, NH2Cl and TauNHCl on hepatic function were investigated in the perfused rat liver. HOCl at a concentration of 2.7 microM resulted in a marked increase in the perfusion pressure and the release of LDH associated with a decrease in bile flow. These effects were abolished by increasing the concentration of extracellular glutathione in the perfusate to physiological levels. NH2Cl (15 microM) and TauNHCl (65 microM) increased the perfusion pressure only slightly, but resulted in significant increases in the biliary excretion of glutathione disulfide, indicating that chloramines are reduced intracellularly by glutathione. The increment in biliary glutathione disulfide depended on the amount of chloramine taken up by the liver. The extraction of NH2Cl averaged 98% compared to 13% for TauNHCl. The present data indicates that intra- and extracellular glutathione plays an important role not only in the detoxification of O2-. and H2O2 generated by activated PMN but also in the protection against the cytotoxic effects of products of myeloperoxidase released by PMN upon activation.
Factors regulating initial rates of bromination, no-carrier-added radiobromination and simultaneously-occurring chlorination by chloramine T were studied using a neuroleptic drug spiperone as the substrate. Besides the factors such as initial concentrations of chloramine T, substrate and bromide ions, upon which the rates were dependent in first, second or zero-order, the water-acetic acid composition or the hydrogen ion concentration of the solutions, where the reactions took place, was found to play a key role. By controlling these factors, optimal radiobromination conditions, where radiobromination proceeds effectively whilst simultaneously-occurring chlorination is kept from proceeding at a high rate, thus resulting in radiobrominated radiopharmaceuticals of high specific activity (10 Ci/mumol) and high radiochemical and chemical purity, could be fulfilled.
Little is known about the biological significance of most pteridines, despite their ubiquitous occurrence in living cells. Seventeen different pteridines were tested for their ability to modulate the growth inhibitory effect of the disinfectant chloramine-T on three different strains of Escherichia coli bacteria. We found striking differences between the pteridine derivatives: whereas aromatic pterins with a hydroxy function at side chain atom C2' increased the growth inhibition, those with a 7,8-dihydro structure exerted a suppressive effect. These results are in excellent agreement with previously observed effects of pteridine derivatives on chloramine-T-induced luminol-dependent chemiluminescence, and together, are highly suggestive of a general interaction of these compounds with oxygen or chlorine free radicals. This interaction is likely to have biological significance and might offer an explanation for the widespread occurrence of pteridines.
The effects of chloramine-T (CT) on monoclonal antibody B72.3 were studied with particular reference to Con-A lectin binding. After exposure to chloramine-T concentrations from 0.8 to 4.0 mg/mL (115-574 mol CT/mol B72.3), B.72.3 showed progressive binding to agarose-linked Con-A. This behavior was paralleled by decreasing immunoreactivity and increasing fragmentation and aggregation of B72.3 demonstrated by SDS-PAGE and size exclusion HPLC.
Effectiveness of Chloramine T trihydrate (N-chloro-p-toluene sulfonamide) on both planktonic and sessile populations of different Legionella pneumophila strains was assessed. Although Chloramine T is a recommended commercial formulation for disinfecting cooling towers, there is a lack of published data about the efficacy of this compound against both planktonic and sessile populations of L. pneumophila. Planktonic L. pneumophila strains were suspended in tap water and sessile L. pneumophila strains were grown on stainless steel which is used in the construction of cooling towers, followed by exposure to the biocide. The sensitivity of both planktonic and sessile populations of L. pneumophila strains was different. The biocide was found effective below recommended dosages (0.1-0.3%) against planktonic populations of L. pneumophila, whereas it was determined that higher dosages than those recommended were required for sessile populations of L. pneumophila. The results indicated that studying only the planktonic populations of L. pneumophila for biocide tests might not be sufficient to provide information about the optimum dosage and contact time. Therefore, efficacy has to be tested on both planktonic and sessile bacteria.
The gating status of the QX-314 bound Na channels before and after suppressing the fast inactivation by chloramine-T (CT) was investigated by studying the gating charge immobilization using the OFF gating current (Ig,OFF). CT treatment, which abolishes the charge immobilization induced by a prolonged depolarization, altered the kinetics of Ig,OFF: the fast phase became insensitive to the pulse duration and the slow phase became three times faster than the control one. However, internally applied QX-314 (in the presence of external TTX) caused an immediate charge immobilization similar to that observed in the absence of CT treatment. The Ig,OFF exhibited kinetics similar to the inactivated channels, decaying with a very fast time course. We conclude that the charge immobilization is restored by QX-314 in the chloramine-T-treated axon and that the gating state of the QX-314-bound channel is similar to the inactivated one. The role of the gating charge immobilization in the use-dependent block mechanism is discussed.
It has been known for years that mixing household cleaning products can be hazardous. Nonetheless, from time to time, episodes of pneumonitis from such mixing occur. Although symptoms range from minor upper respiratory irritation to adult respiratory distress syndrome, deaths are very rare. We present the case of a woman with an undiagnosed oligodendroglioma who mixed bleach and ammonia (resulting in the formation of chloramine gas), and died while cleaning her bathroom. To our knowledge, this is the first such death reported from chloramine gas intoxication.
A case is discussed of eosinophilic bronchial inflammation without asthma due to chloramine T (CLT) exposure in a nurse. She reported a non-productive chronic cough on contact with CLT during workshifts. She had negative results of skin prick testing to CLT. However, sensitisation to CLT was confirmed by the presence of specific anti-chloramine IgE. Airway responsiveness to histamine was normal before and after CLT challenge. Eosinophil proportion in sputum was increased at 6 and 24 h after CLT challenge.
Rous-associated virus-6I was used as a model for studying the labelling specificity of the chloramine-T iodination procedure when applied to intact enveloped viruses. The specificity of labelling depended markedly on the concentration of iodide in the reaction mixture. At low concentrations of iodide (below 0-5 muM) only the surface proteins and lipid of intact virions were iodinated; there was no detectable labelling of internal proteins. At 10 muM-iodide, however, both internal and external proteins were iodinated; moreover there was a marked change in the reactivity of the surface proteins. It appears that the lipid envelope provides an effective barrier to the iodinating complex generated at low, but not at high, concentrations of iodide. These and other observations suggest that the chloramine-T procedure has a previously unrecognized potential for specifically labelling the surface proteins of lipid-enveloped structures.
A procedure for the preparation of chloramine-T (CT) conjugates used to assay IgE antibodies was developed using response surface methodology and serum from a subject occupationally exposed to the substance. The conjugates, synthesized by reacting CT with human serum albumin (HSA) and other protein carriers, were used as antigens in a radio-allergosorbent test (RAST). Human serum albumin was found to be a suitable carrier, although other protein carriers also gave specific IgE-binding of a similar extent. The CT-HSA conjugates used in the RAST were characterized by high performance liquid chromatography, electrophoresis, immunodiffusion and ammonium sulphate precipitation. However, no strong correlation was seen between the ability of the conjugates to bind IgE and their physical or immuno-chemical properties. The hapten and carrier specificity of CT-induced IgE antibodies in the subject's serum were studied by direct RAST and RAST inhibition. No existence of new antigenic determinants related to the carrier could be demonstrated. Although HSA as a carrier was altered immunochemically by CT, the IgE antibodies were found to be specific to hapten only. Chloramine-T-specific IgG antibodies could not be demonstrated in the subject's serum.
Antimicrobial activity of the following four new N-chloramine compounds was evaluated: two chlorinated simple amino acids, a chlorinated half-ester of succinic acid, and a chlorinated half-ester of glutaric acid. For comparison, the known bactericidal agents 3-chloro-4,4-dimethyl-2-oxazolidinone and chlorhexidine were evaluated by the same procedure. The contact germicidal efficiency screen was used to examine the in vitro bactericidal activity of all six compounds in the absence and presence of 5% horse serum or 5% Triton X-100. The four new compounds were found to have greater germicidal activity than the other compounds tested and to exhibit low toxicity and skin irritation values. The in vivo bactericidal activity was evaluated in two studies. In the occlusion test, three of the four new compounds plus chlorhexidine diacetate were tested. The N-chloramines were significantly superior to chlorhexidine in preventing the expansion of the normal flora under occlusion. In the scrub test, a gloved-hand wash method was used to compare the antimicrobial effect of a 1% solution of the chlorinated half-ester of succinic acid in triacetin with that of a commercial germicidal hand wash containing 4% chlorhexidine gluconate. The two preparations exhibited essentially the same hand-degerming activity.
Growth of Enterobacter cloacae on various media was compared after disinfection. This was done to examine the effects of monochloramine and chlorine on the enumeration of coliforms. The media used were TLY (nonselective; 5.5% tryptic soy broth, 0.3% yeast extract, 1.0% lactose, and 1.5% Bacto-Agar), m-T7 (selective; developed to recover injured coliforms), m-Endo (selective; contains sodium sulfite), TLYS (TLY with sodium sulfite), and m-T7S (m-T7 with sodium sulfite). Sodium sulfite in any medium improved the recovery of chloramine-treated E. cloacae. However, sodium sulfite in TLYS and m-T7S did not significantly improve the detection of chlorine-treated E. cloacae, and m-Endo was the least effective medium for recovering chlorinated bacteria. Differences in recovery of chlorine- and chloramine-treated E. cloacae are consistent with mechanistic differences between the disinfectants.