Сульфаметизол

Description

Sulfamethizole is an antibacterial substance of the sulfonamide group, 4-amino-N-(5-methyl-1,3,4-thiadiazol-2-yl)benzenesulfonamide. The heterocycle of the sulfamide nitrogen is 5-methyl-1,3,4-thiadiazole, therefore the substance is classified as a thiadiazole sulfonamide. The action is bacteriostatic: the molecule repeats the geometry of para-aminobenzoic acid and competitively blocks dihydropteroate synthase, which is why the assembly of dihydrofolic acid in the bacterial cell stops, and then the synthesis of purines and pyrimidines. Human cells do not have this enzyme target - folate comes from food, which is what selectivity is based on.

Identification

• CAS No.: 144-82-1
• Chemical Formula: C9H10N4O2S2
• Molecular weight: 270.33; exact weight: 270.33
• EU number: 205-641-1
• UNII: 25W8454H16
• NSC number: 757327
• DSSTox ID: DTXSID5023615
• NCI Thesaurus Code: C47736
• RTECS number: WP0875000
• HS code: 2935904000
• ATC code: B - blood and hematopoietic system; D - dermatological preparations; J - anti-infective drugs of systemic action; S - sense organs

Physico-chemical properties

• Appearance: White powder (NTP, 1992)
• Color and shape: water crystals, colorless crystal
• Density: 1.4704 (estimated)
• Melting point: 208 °C
• Boiling point: 176 °C (estimated; model derived and below melting point)
• Flash point: 259.1 ± 30.7 °C
• Refractive index: 1.6440 (estimate)
• Solubility in water: more than 40.5 μg/ml; according to the classification of reactivity, the substance is classified as insoluble in water
• Vapor pressure: 2.06 × 10⁻⁹ mm Hg. Art. at 25 °C (estimated)
• Henry's Law Constant: 2.63 × 10⁻¹⁴ atm m³/mol at 25 °C (estimate)
• Dissociation constants: pKa1 = 2.1 (amino group); pKa2 = 5.3 (fragment R1SO2NHR2)
• PSA Specifications: 135
• XLogP3: 0.5
• Rate constant for reaction with hydroxyl radicals: 2.39 × 10⁻¹¹ cm³/(molecule s) at 25 °C (estimated)
• Storage conditions: 2–8 °C

Ion mobility data

Collision Cross Section (CCS), Type TW:

• 155.2 Ų [M+H]⁺ - calibrated to polyalanine and drug standards
• 152.2 Ų [M+H]⁺
• 157.8 Ų [M+H]⁺ - Waters Major Mix calibration
• 171.2 Ų [M+Na]⁺ - Waters Major Mix calibration

Experimental properties: complexation

Sulfamethizole has been studied as a ligand in Schiff bases derived from 5-bromosalicylicaldehyde. The electronic absorption spectra of Cu(II), Ni(II) and Co(II) chelates with Schiff bases of 5-bromosalicylicaldehyde and sulfamethoxypyridazine, sulfamethizole and sulfafurazole (sulfisoxazole) in dimethyl sulfoxide solution were studied. All chelates give an intense charge transfer band at the blue end of the visible region, the stereochemistry is described by d-d transition bands; Ni(II) and Co(II) chelates are 6-coordinated in all cases.

For the same Cu(II), Co(II) and Ni(II) chelates, an atomic absorption spectrometric method for determining the metal is described. The stoichiometry was 1:1 for all compounds, the found metal content coincided with the theoretical one. The structure was confirmed by IR spectrometry and X-ray diffraction. Thermogravimetry showed: the decomposition of Schiff bases themselves begins at 200–290 °C, chelates at 60–120 °C, stable oxides are formed at 530–800 °C; Orders and activation energies were calculated for individual decomposition reactions. The formation and stability of these chelates were also studied in an ethanol-acetone medium (70:30 v/v).

Scope of application

• Pharmaceutical substance: short-acting sulfonamide, half-life from plasma is about 2.5 hours, protein binding is about 85%, about 60% of the dose is excreted in the urine in 5 hours. High concentration in urine with low concentration in plasma determined the main indication - acute uncomplicated urinary tract infections. Trade names: Thiosulfil, Urolucosil, Microsul, Rufol, Sulfstat, Urodiaton, Thiosulfil Forte, Renasul, Metazol.
• Analytical standard for monitoring residual amounts of sulfonamides in meat, milk, aquaculture products and environmental materials using HPLC-MS/MS methods.
• Organic synthesis reagent and ligand in coordination chemistry - see section on Schiff base chelates.

Toxicity

• LD50 oral, rat: 3500 mg/kg

Safety Information

• Tags: Xi
• Hazard Statements: H317 - May cause an allergic skin reaction
• Precautionary statements: P280
• Hazard class code: 43
• Safety instructions: 36/37
• WGK Germany: 2
• Transport codes: NONH for all types of transport (not included in the list of dangerous goods)
• Reactive group according to CAMEO classification: azo-, diazo-, azido-, hydrazine and azide compounds
• Reactions with air and water: insoluble in water, does not give rapid reactions

Storage, handling and disposal

Keep in a tightly closed container at 2–8 °C, protect from light and moisture. Wear gloves and protective clothing: the main danger is skin sensitization; repeated contact with dust is unacceptable. Hanging should be carried out using a local hood.

Disposal. The criteria for treatment on the ground and disposal at sanitary landfills were being revised at the time the card was drawn up, therefore, before placing waste on the ground, agree on the method with the environmental regulator. Discharge with wash water into the sewer system is not permitted.