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Effect of sulfonation on the cell and tissue distribution of the photosensitizer aluminum phthalocyanine.

Aluminum sulfonated phthalocyanine has potential as a suitable photosensitizer for use in the photodynamic therapy of cancer. In the present study, cellular uptake and retention of the individual mono-, di-, tri-, and tetrasulfonated derivatives (AlS1-4Pc) were examined in tissue culture and in normal and neoplastic tissue of tumor-bearing mice. Uptake and retention of the various derivatives by cells in tissue culture correlated inversely with the degree of sulfonation. Accordingly, Colo 26 cells in monolayer culture, 24 h after addition of 10 microM of appropriate photosensitizer, had accumulated approximately 25-fold more AlS1Pc than AlS3Pc and retained this species longer than more sulfonated derivatives. In contrast to these in vitro results, it was found that Colo 26 growing s.c. in BALB/c mice accumulated photosensitizer to a greater extent when the degree of sulfonation increased, such that A1S4Pc greater than AlS3Pc greater than AlS2Pc greater than AlS1Pc. By 24-48 h after the i.v. injection of 0.1 ml 2.27 mM solution of individual photosensitizer, the relative ratios of tumor:adjacent tissue varied from greater than 10:1 to greater than 2:1, showing that selective tumor uptake may be affected profoundly by the composition of the phthalocyanine compound. The livers and spleens of both normal and tumor-bearing mice, unlike other normal tissue, took up the sulfonated derivatives in an order that provided a mirror image of that observed in neoplastic tissue. These complex in vivo distribution and retention characteristics appear to be a consequence of relative hydrophilicity/hydrophobicity properties of the sulfonated species and indicate the extent to which these characteristics may influence photosensitizer distribution and accumulation.

Animals↗

Synthesis and metabolism of sodium 3 alpha,7 alpha-dihydroxy-25,26-bishomo-5 beta-cholane-26-sulfonate in the hamster.

This paper reports the chemical synthesis of a new bile acid analogue, namely sodium 3 alpha,7 alpha-dihydroxy-25,26-bishomo-5 beta-cholane-26-sulfonate (bishomoCDC-sul) from chenodeoxycholic acid and describes its metabolism in the hamster. The structure of the new compound was confirmed by proton and carbon-13 nuclear magnetic resonance spectroscopy. After intravenous infusion of [3H]-labeled sulfonate into bile fistula hamsters, it was extracted by the liver and secreted into the bile; more than 65% of the radioactivity was recovered in the bile within 1 h. Following intraduodenal administration of the [3H]sulfonate and [14C]chenodeoxycholyltaurine, both compounds were excreted into the bile more slowly; only 41 and 43% of the radioactivity, respectively, were recovered in the bile during the four-hour experimental period. In contrast, when the labeled compounds were injected into the terminal ileum, both the sulfonate and chenodeoxycholyltaurine were rapidly absorbed and secreted into the bile; 84 and 97%, respectively, of the radioactivity were recovered during a four-hour period. Chromatographic analysis demonstrated that in these short-term experiments most (> 95%) of the sulfonate was secreted into the bile without biotransformation regardless of the route of administration. When infused intravenously at increasing doses, bishomoCDC-sul induced cholestasis at an infusion rate of 1 mumol/min/kg. These results suggest that sodium 3 alpha,7 alpha-dihydroxy-25,26-bishomo-5 beta-cholane-26-sulfonate was absorbed from the terminal ileum by active transport, extracted by the liver, and secreted into the bile in a manner similar to that of the natural bile acids.

Animals↗

Modification of the antiepileptic actions of phenobarbital and phenytoin by the taurine transport inhibitor, guanidinoethane sulfonate.

We investigated whether chronic administration of guanidinoethane sulfonate, an inhibitor of taurine uptake, could modify the antiepileptic actions of phenobarbital and phenytoin on maximal electroshock seizures in mice. Treatment with 1% guanidinoethane sulfonate decreased the taurine concentration in the brain to 76% of the control value. Under these conditions, neither the severity of tonic convulsions of maximal electroshock seizures nor the threshold for tonic extension caused by electroshock was altered. However, treatment with guanidinoethane sulfonate lessened the antiepileptic actions of phenobarbital and phenytoin on electroshock seizures. The brain concentrations of phenobarbital and phenytoin were unaltered by administration of guanidinoethane sulfonate. The brain concentrations of guanidinoethane sulfonate and total guanidino compounds were unchanged by the injection of either phenobarbital or phenytoin. It is suggested that the observed loss of anticonvulsive potency of phenobarbital and phenytoin may have been related to the decrease in taurine concentration produced by guanidinoethane sulfonate.

Amino Acids↗

Topical capsaicin administration protects against trinitrobenzene sulfonic acid-induced colitis in the rat.

We used the [3H]resiniferatoxin binding assay to demonstrate for the first time the existence of vanilloid receptors in the rat colon and to explore their expression during trinitrobenzene sulfonic acid-induced colitis. Membranes obtained from control colon bound [3H]resiniferatoxin with an affinity of 3 nM; the receptor density was 450 fmol/mg protein or 9 fmol/mg wet weight. Capsaicin and capsazepine, a competitive antagonist of capsaicin, inhibited specific resiniferatoxin binding with Ki values of 3 microM and 0.1 microM, respectively. Trinitrobenzene sulfonic acid induced a very rapid ulceration in the colon: 1 h after treatment 90% of the colon showed ulcerative damage. Coadministration of 640 microM capsaicin diminished the ulcerative effect of trinitrobenzene sulfonic acid to 64% when examined 1 h after trinitrobenzene sulfonic acid challenge; however, this protective action was lost 23 h later. Colon samples obtained 4 h, 24 h, and 1 week after trinitrobenzene sulfonic acid challenge bound resiniferatoxin, capsaicin, and capsazepine with affinities similar to those of control samples. The receptor density remained at an essentially constant level when expressed in fmol/mg protein but, in keeping with the increased wet weights, showed a reduction when expressed in fmol/mg wet weight. We conclude that acute capsaicin administration protects against the ulcerative action of trinitrobenzene sulfonic acid, most likely via the release of protective neuropeptides from capsaicin-sensitive nerve endings. The loss of this protective action is presumably due to a depletion of the protective neuropeptides rather than to a loss of vanilloid (capsaicin) receptors.

Administration, Topical↗

Synthesis and biological activities of leukotriene F4 and leukotriene F4 sulfone.

Leukotriene F4 (LTF4) and LTF4 sulfone have been synthesized and their biological activities determined in the guinea pig. In vitro LTF4 displayed comparable activity to LTD4 on guinea pig trachea and parenchyma but was less active on the ileum. When injected intravenously into the guinea pig, LTF4 induced a bronchoconstriction (ED50 16 micrograms Kg-1) which was blocked by indomethacin and FPL-55712 and was 50-100 X less potent than LTD4 in this assay. LTF4 sulfone was approximately 2-5 times less active than LTF4 in vitro and in vivo. When injected into guinea pig skin with PGE2 (100 ng); LTF4 and LTF4 sulfone (10-1000 ng) induced changes in vascular permeability. The order of potency in this assay was LTE4 sulfone = LTD4 = LTD4 sulfone greater than LTE4 greater than LTF4 = LTF4 sulfone.

Animals↗

Primary biodegradation of linear alkyltoluene and alkylbenzene sulfonates.

Studies on the primary biodegradation of linear dodecylbenzene sulfonate, linear dodecyltoluene sulfonate, linear C(10-14) benzene sulfonate, linear C(10-14) toluene sulfonate, commercial samples of linear C(10-14) benzene sulfonate and branched dodecylbenzene sulfonate (DDBS) were carried out using a microbial culture developed from garden soil. Results show that linear alkyl toluene (LAT) is as degradable as linear alkylbenzene (LAB) in 7 days. However, a slower rate of degradation was noted with LAT. Various distributions of the positional isomers of the phenyl ring in the alkane chain of C(10-14) LAB showed no change in the pattern of primary biodegradation.

Journal Article↗

Biodistribution and tumor uptake of [67Ga]chlorogallium-tetraoctadecyloxy phthalocyanine and its sulfonation products in tumor bearing C3H mice.

To evaluate the biodistribution and tumor uptake of chlorogallium tetraoctadecycloxy phthalocyanine, a potential new drug for the photodynamic therapy of cancer, we prepared the radioactive 67Ga-labeled complex and its water soluble sulfonated derivative. The non-sulfonated dye was obtained by condensation of octadecyloxyphthalonitrile in the presence of a mixture of 67Ga and 69Ga chloride. The sulfonated derivative was obtained by treatment of the condensation product with oleum. As singlet molecular oxygen has been implicated in the photodynamic action of phthalocyanines (Pcs), the quantum yield of singlet oxygen (phi delta) was evaluated for chlorogallium tetraoctadecyloxy Pc, and also its zinc, aluminum and metal free analogues. After intraperitoneal administration of the non-sulfonated dye into RIF tumor bearing C3H mice, a very high 67Ga-uptake was observed in the spleen, while tumor radioactivity remained low during the 3 day study. The in vivo stability of the 67Ga-phthalocyanine complex was confirmed by comparing the distribution pattern with that of 67Ga-citrate, which proved to be significantly different. Intravenous injection of the sulfonated dye resulted in an overall lowering of 67Ga-uptake by most tissues, particularly in the spleen, while tumor radioactivities were slightly higher. These data suggest that amphiphilic photosensitizers, containing both polar sulfonate groups and long aliphatic substituents, exhibit the best distribution pattern for both imaging and photodynamic therapy of tumors.

Animals↗

Preparation of a sulfonated fused-silica capillary and its application in capillary electrophoresis and electrochromatography.

In the present paper, two new methods, sol-gel and chemical bonding methods, were proposed for preparation of sulfonated fused-silica capillaries. In the sol-gel method, a fused-silica capillary was coated with the sol solution obtained by hydrolysis of 3-mercaptopropyltrimethoxysilane (MPTS) and tetramethoxysilane, and followed by age; while in the chemical bonding method, a capillary was chemically bonded directly with MPTS. Then, both the resulting capillaries were oxidized with an aqueous solution of hydrogen peroxide solution (H2O2) (30%, m/m) to obtain the sulfonated capillaries. The electroosmotic flow (EOF) for the sulfonated capillaries was found to remain almost constant within the studied pH range, and greater than that of the uncoated capillary. However, the coating efficiency of the capillary prepared by chemical bonding method was higher than that by sol-gel method, by comparing their magnitude of the EOF, the degree of disguise of the silanol and reproducibility of preparation procedure. The effects of the electrolyte's concentration and the content of methanol (MeOH) on the EOF were also studied. Especially, the study of the apparent pH (pH*) on the EOF in a water-MeOH system was reported. Finally, capillary electrophoretic separation of seven organic acids was achieved within 6.5 min under optimal condition using the chemically bonded sulfonated capillary. Moreover, separation of four alkaloids on the sulfonated capillary was compared with that on uncoated capillary in different conditions. Ion-exchange mechanism was found to play a key role for separation of these four basic analytes on the sulfonated capillary.

Alkaloids↗

Sulfonated naphthyl porphyrins as agents against HIV-1.

Sulfonated 5,10,15,20-tetra(1-naphthyl)porphyrin (T1NapS) and 5,10,15,20-tetra(2-naphthyl)porphyrin (T2NapS) and their copper and iron chelates show activity against the human immunodeficiency virus (HIV-1). The porphyrins were prepared by sulfonation of the parent structures with sulfuric acid. More highly sulfonated structures were prepared by sulfonation for longer times. Matrix-assisted laser desorption/ionization (MALDI) mass spectrometry showed species with as many as eight sulfonates. Some of the mass spectral peaks for the copper chelates were consistent with loss of water, apparently from intramolecular sulfone formation between two adjacent naphthalene rings that took place during copper insertion. The compounds could be separated using capillary electrophoresis; addition of beta- or gamma-cyclodextrin gave substantially better separation of the components. Activity against HIV was evaluated using an epithelial HeLa-CD4-CCR5 cell line; EC50 values for HIV-1 IIIB and HIV-1 JR-FL ranged from 1 to 15 microg/ml. The compounds exhibit low toxicity for human epithelial cells and have potential as microbicides which might be used to provide protection against sexual transmission of HIV.

Alkanesulfonates↗

Sulfonation of poly(N-vinylcarbazole) studied by combined time-of-flight secondary ion mass spectrometry and X-ray photoelectron spectroscopy

A series of sulfonated poly(N-vinylcarbazole) (PVK) samples have been systematically studied by time-of-flight secondary ion mass spectrometry (TOF-SIMS) and X-ray photoelectron spectroscopy (XPS). Negative TOF-SIMS results provided unambiguous evidence that sulfonate groups are chemically attached to the carbazole moiety of PVK. The positive SIMS spectrum of PVK was, however, little affected by the sulfonation reaction. The degree of sulfonation was quantitatively determined by XPS. Therefore, the combination of TOF-SIMS and XPS is useful to follow the sulfonation reaction, both qualitatively and quantitatively. The SIMS intensities of some characteristic fragments are linearly related to the degree of sulfonation, suggesting that quantitative analysis is possible from TOF-SIMS data.

Journal Article↗

Quantitative determination of fluorotelomer sulfonates in groundwater by LC MS/MS.

Aqueous film-forming foams (AFFF) are complex mixtures containing fluorocarbon- and hydrocarbon-based surfactants that are used to fight hydrocarbon-fueled fires. The military is the largest consumer of AFFF in the United States, and fire-training activities conducted at military bases have led to groundwater contamination by unspent fuels and AFFF chemicals. A direct-injection, liquid-chromatography tandem mass spectrometry (LC MS/MS) method was developed to quantify a suite of fluorotelomer sulfonate surfactants in groundwater collected from military bases where fire-training activities were conducted. The 4:2, 6:2, and 8:2 fluorotelomer sulfonates were detected and quantified in groundwater from two of the three military bases. The total fluorotelomer sulfonate concentrations observed at Wurtsmith AFB, MI, and Tyndall AFB, FL, ranged respectively from below quantitation (< or = 0.60) to 182 microg/L and from 1100 to 14,600 microg/L. Analyses of a fluorotelomer-based AFFF concentrate by negative ion fast atom bombardment/mass spectrometry and LC MS/MS analyses indicate that the AFFF concentrate contains only a small amount of fluorotelomer sulfonates and that fluoroalkylthioamido sulfonates are the main anionic fluorosurfactant in the mixtures. More research is needed to determine the fate of fluoroalkylthioamido sulfonates in the environment.

Alkanesulfonates↗

Dinuclear calcium complex with weakly NH...O hydrogen-bonded sulfonate ligands.

The novel intramolecularly NH...O hydrogen-bonded Ca(II)-aryl sulfonate complex, [Ca2(SO3-2-t-BuCONHC6H4)2(H2O)4]n(2-t-BuCONHC6H4SO3)2n (1), sulfonate anion, (HNEt3)(SO3-2-t-BuCONHC6H4) (2a), (PPh4)(SO3-2-t-BuCONHC6H4) (2b), (n-Bu4N)(SO3-2-t-BuCONHC6H4) (2c), and sulfonic acid, 2-t-BuCONHC6H4SO3H (3), were synthesized. The structures of 1, 2a, and 2b depict the presence of the formation of NH...O hydrogen bonds between the amide NH and S-O oxygen for a series of compounds as determined by IR and 1H NMR analyses both in the solid state and in the solution state. Thus, the NH...O hydrogen bonds with neutral amide groups are available for investigation of the electronic state of the O- anion. The combined data from the IR and 1H NMR spectra indicate that the sulfonic acid, sulfonate anion, and Ca(II) complex have a substantially weak intramolecular NH...O hydrogen bond between the SO3 oxygen and amide NH. In the detailed comparison with the intense NH...O hydrogen bonds for the carboxylate, weak NH...O hydrogen bonds for sulfonate is due to the strong conjugation of the SO3- group with the lower nucleophilicity.

Journal Article↗

Optimized separation and determination of methyl sulfone metabolites of polychlorinated biphenyls (PCBs) and p,p'-DDE in biota samples.

An optimised method is described for the determination of 27 methyl sulfone polychlorobiphenyls (PCBs) and DDE in biota samples. Initially, the samples were extracted by hot Soxhlet and the methyl sulfones were separated by liquid/liquid extraction with concentrated sulfuric acid and back-extracted with hexane. The parameters of the back-extraction were studied and it was found that for a quantitative extraction of the methyl sulfones from the concentrated acid layer, a 50% dilution with cold water should be done. The hexane layer containing the methyl sulfones was further cleaned-up on basic silica (33% KOH) and Florisil. After concentration, the extract was analysed by gas chromatography-mass spectrometry (GC-MS) with electron capture negative ionisation (ECNI) in selected ion monitoring mode (SIM). It was shown that, for methyl sulfones, the ion formation was dependent on the chlorine substitution, position of the MeSO2-group and the ion source temperature. If the ion source temperature was higher than 200 degrees C, [M-CH3]- was the predominant ion for most methyl sulfones. Therefore, for increased sensitivity, quantitation of most congeners was done using [M-CH3]- ions instead of the molecular ion as used in previously reported methods. The method was validated for the determination of 26 tri- to hepta- 3- and 4-substituted MeSO2-PCBs and 3-MeSO2-DDE in animal and human tissues. Good sensitivity and selectivity of the method were obtained. Limits of detection (LODs) ranged from 0.06 to 0.10 ng g(-1) lipid weight. Average recoveries of individual congeners from vegetable oil spiked with individual standards (3.33 ng g(-1)) ranged from 73 to 112% with a mean value of 89%. The coefficients of variation ranged from 5.2 to 12.2%, which is within the acceptable range for environmental analyses.

Adipose Tissue↗

Comparative efficacy of thallium adsorption by activated charcoal, prussian blue, and sodium polystyrene sulfonate.

BACKGROUND: Although Prussian blue is considered the antidote of choice for thallium poisoning, the lack of a Food and Drug Administration-approved pharmaceutical formulation has led to the search for other adsorbents. Activated charcoal has been demonstrated to adsorb thallium in vitro, and the similarity between thallium and potassium has led some authors to consider the use of sodium polystyrene sulfonate as a potential adsorbent. This experiment was designed to compare the relative thallium binding efficacy of these agents in a standard isotherm model. METHODS: A standard aqueous solution of thallium acetate buffered to pH 7.0 was agitated at 25 degrees C with activated charcoal, Prussian blue, or sodium polystyrene sulfonate at adsorbent:thallium ratios ranging from 1.5:1 to 100:1. In order to further simulate physiologic conditions, all trials were repeated in a solution containing 4 mmol/L potassium phosphate. After thorough agitation, the mixtures were allowed to settle and were centrifuged and filtered through a 0.22-micron filter. Supernatant thallium concentrations were measured by atomic absorption spectrophotometry. Langmuir isotherms were used to calculate the maximal adsorptive capacity of each adsorbent, using linear regression with Pearson's correlation coefficients (r). Maximal adsorptive capacities were compared statistically with a p < 0.05 considered significant. RESULTS: The maximal adsorptive capacities defined as milligrams of thallium per gram of adsorbent (shown with linear regression p and r values) were as follows: activated charcoal, 59.7 mg/g (p = 0.005, r = 0.995); Prussian blue, 72.7 mg/g (p = 0.004, r = 0.996); and sodium polystyrene sulfonate, 713 mg/g (p = 0.049, r = 0.951). All three values were statistically different from each other. At a physiologic potassium concentration, the maximal adsorptive capacities for activated charcoal and Prussian blue were essentially unchanged (58.3 mg/g and 69.8 mg/g, respectively, p > 0.05 for each vs trials without potassium), while the maximal adsorptive capacity for sodium polystyrene sulfonate fell to 39.1 mg/g (p = 0.003, r = 0.997, p = 0.005 vs sodium polystyrene sulfonate without potassium). CONCLUSIONS: This in vitro study confirms the utility of Prussian blue and activated charcoal as thallium adsorbents. Although sodium polystyrene sulfonate demonstrates exceptional in vitro adsorption of thallium, its greater affinity for potassium probably renders it clinically ineffective.

Adsorption↗

A specific gas chromatographic analysis for cysteinyl-S-sulfonate residues in physiologically significant proteins treated with sulfite.

It has been shown in previous studies that when sulfite is absorbed by rabbits via either inhalation of SO2 or oral exposure to sulfite, the hydrated form, bisulfite, interacts with plasma disulfides where it is suspected to be in the form, cysteine-S-sulfonate. A rapid and specific gas chromatographic analysis procedure for cysteine-S-sulfonate has been developed to better study the distribution of sulfite in biological systems. Sulfonated proteins are enzymatically hydrolyzed to ensure stability of the acid labile S-sulfonate disulfide. The hydrolysate is then applied to a 6 cm cation-exchange column and eluted with 0.1 N HCl, which elutes the acidic cysteine-S-sulfonate with the void volume of the column, leaving behind any remaining cysteine. The silylated derivatives of the column effluent are prepared using Tri-Sil/BSA. These derivatives are injected into a gas chromatograph equipped with a flame-photometric detector operating in the sulfur mode, 2% OV-101 on Chromosorb W/HP 1/4 inch glass column, oven temperature 140 degrees C, and carrier flow rate of 86 mL/min. The presence of cysteine-S-sulfonate in sulfite-treated rabbits has been directly determined by the described method.

Animals↗

Guanidinoethane sulfonate and the disposition of dietary taurine in the rat.

Guanidinoethane sulfonate, a transport antagonist of taurine in brain synaptosomes and isolated perfused hearts, causes profound and rapid depletion of tissue taurine levels when given to rats as a 1% solution. In tissues outside of the central nervous system, guanidinoethane sulfonate on average decreased by half the absolute amount of taurine obtained from the diet. However, the percent of taurine derived from the diet increased from an average of 36% to an average of 58%. In the brain, guanidinoethane sulfonate had little effect on the absolute amount of taurine obtained from the diet, but increased the percent contribution of diet from an average of 60% to an average of 80%. Guanidinoethane sulfonate had no effect on the tissue:serum ratio of radioactivity in brain, thymus, muscle or pancrease 24 hours after an injection of [3H]taurine. However, other tissues showed significant decreases in tissue:serum ratio, ranging from 67% of control in the small intestine to 36% of control in the liver. In its taurine-depleting action, therefore, guanidinoethane sulfonate discriminates between taurine derived from diet and taurine derived from biosynthesis. I conclude that the taurine-depleting action of guanidinoethane sulfonate is complex in mechanism, being a combination of inhibition of transport and interference with synthesis.

Animals↗

Patterns of soft C-H...O hydrogen bonding in diaryl sulfones.

In bis(4-tolyl) sulfone, C(14)H(14)O(2)S (1), 2,5,4'-trimethyldiphenyl sulfone, C(15)H(16)O(2)S (2), and 4-chlorodiphenyl sulfone, C(12)H(9)ClO(2)S (3), the molecules are linked by soft C-H...O hydrogen bonds into three different types of one-dimensional aggregate: simple chains in (1), molecular ladders in (2) and chains of fused rings in (3). In each of 3,4-dimethyl-4'-chlorodiphenyl sulfone, C(14)H(13)ClO(2)S (4), and 2,5-dimethyldiphenyl sulfone, C(14)H(14)O(2)S (5), the C-H...O hydrogen bonds link the molecules into two different types of two-dimensional sheet, based on a (4,4) net in (4) and a (3,6) net in (5). The patterns of soft C-H...O hydrogen bonds in (1)-(5) are compared with those in other diaryl sulfones, mainly retrieved from the Cambridge Structural Database, whose substitution patterns preclude the formation of hard hydrogen bonds. Observed aggregation modes range from the formation of no C-H...O hydrogen bonds at all, via finite (zero-dimensional) arrays through one-, two- and three-dimensional systems.

Journal Article↗

Crystal structures of the trifluoromethyl sulfonates M(SO3CF3)2 (M = Mg, Ca, Ba, Zn, Cu) from synchrotron X-ray powder diffraction data.

The crystal structures of divalent metal salts of trifluoromethyl sulfonic acid ("trifluoromethyl sulfonates") M(SO(3)CF(3))(2) (M = Mg, Ca, Ba, Zn, Cu) were determined from high-resolution X-ray powder diffraction data. Magnesium, calcium and zinc trifluoromethyl sulfonate crystallize in the rhombohedral space group R(bar)3. Barium trifluoromethyl sulfonate crystallizes in the monoclinic space group I2/a(C2/c) and copper trifluoromethyl sulfonate crystallizes in the triclinic group P(bar)1. Within the crystal structures the trifluoromethyl sulfonate anions are arranged in double layers with the apolar CF(3) groups pointing towards each other. The cations are located next to the SO(3) groups. The symmetry relations between the different crystal structures have been analysed.

Journal Article↗