Silver sulfadiazine (AgSD) is a sulfonamide antibiotic. The sulfadiazine moiety (SD-SDZ) exerts a dual (bifunctional) inhibitory effect on bacterial growth, preventing bacterial folic acid absorption and subsequent DNA synthesis. Silver sulfadiazine releases silver that binds to and disrupts DNA structure, preventing bacterial DNA from replicating.

Physicochemical Properties

Molecular Formula	C10H9AGN4O2S
Molecular Weight	357.14
Exact Mass	355.949
CAS #	22199-08-2
PubChem CID	441244
Appearance	White to off-white solid powder
Density	1.496g/cm3
Boiling Point	512.6ºC at 760 mmHg
Melting Point	285 °C (dec.)(lit.)
Flash Point	263.8ºC
Vapour Pressure	1.28E-10mmHg at 25°C
LogP	3.114
Hydrogen Bond Donor Count	1
Hydrogen Bond Acceptor Count	6
Rotatable Bond Count	3
Heavy Atom Count	18
Complexity	327
Defined Atom Stereocenter Count	0
SMILES	O=S([N-]C1=NC=CC=N1)(C2=CC=C(N)C=C2)=O.[Ag+]
InChi Key	UEJSSZHHYBHCEL-UHFFFAOYSA-N
InChi Code	InChI=1S/C10H9N4O2S.Ag/c11-8-2-4-9(5-3-8)17(15,16)14-10-12-6-1-7-13-10;/h1-7H,11H2;/q-1;+1
Chemical Name	silver;(4-aminophenyl)sulfonyl-pyrimidin-2-ylazanide
HS Tariff Code	2934.99.9001
Storage	Powder-20°C 3 years 4°C 2 years In solvent -80°C 6 months -20°C 1 month Note: Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture.
Shipping Condition	Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

Biological Activity

ln Vitro	In order to study bacterial infections in burns, silver sulfadiazine (AgSD) is used topically[2].
ADME/Pharmacokinetics	Absorption, Distribution and Excretion Very limited penetration through the skin. Only when applied to very large area burns is absorption into the body generally an issue. Metabolism / Metabolites The degradation of sulfonamides has two different pathways: the N-acetylation pathway which is genetically determined and saturable, and the cytochrome P450 pathway which produces toxic hydroxylamine metabolites "detoxified" by glutathione. (A2885)
Toxicity/Toxicokinetics	Toxicity Summary Studies utilizing radioactive micronized silver sulfadiazine, electron microscopy, and biochemical techniques have revealed that the mechanism of action of silver sulfadiazine on bacteria differs from silver nitrate and sodium sulfadiazine. Silver sulfadiazine acts only on the cell membrane and cell wall to produce its bactericidal effect. A specific mechanism of action has not been determined, but silver sulfadiazine's effectiveness may possibly be from a synergistic interaction, or the action of each component. Silver is a biocide, which binds to a broad range of targets. Silver ions bind to nucleophilic amino acids, as well as sulfhydryl, amino, imidazole, phosphate, and carboxyl groups in proteins, causing protein denaturation and enzyme inhibition. Silver binds to surface membranes and proteins, causing proton leaks in the membrane, leading to cell death. Sulfadiazine is a competitive inhibitor of bacterial para-aminobenzoic acid (PABA), a substrate of the enzyme dihydropteroate synthetase. The inhibited reaction is necessary in these organisms for the synthesis of folic acid. Toxicity Data LD50: 10001 mg/kg (oral, rat)
References	[1]. Strydom SJ, et al. Poly(amidoamine) dendrimer-mediated synthesis and stabilization of silver sulfonamide nanoparticles with increased antibacterial activity. Nanomedicine. 2013;9(1):85-93. [2]. Munhoz DR, et al. Alginate films functionalized with silver sulfadiazine-loaded [Mg-Al] layered double hydroxide as antimicrobial wound dressing. Int J Biol Macromol. 2019;141:504-510.
Additional Infomation	Silver(1+) sulfadiazinate is a silver salt, a sulfonamidate and a member of pyrimidines. It has a role as an antimicrobial agent and an antibacterial drug. It contains a sulfadiazinate. Silver sulfadiazine is a sulfa derivative topical antibacterial used primarily on second- and third-degree burns. Silver sulfadiazine is a Sulfonamide Antibacterial. Silver Sulfadiazine is a sulfonamide-based topical agent with antibacterial and antifungal activity. Silver sulfadiazine may act through a combination of the activity of silver and sulfadiazine. When this agent interacts with sodium chloride-containing body fluids, silver ions are released slowly and sustainably into wounded areas. Ionized silver atoms catalyze the formation of disulfide bonds leading to protein structural changes and inactivating thiol-containing enzymes; silver ions may also intercalate DNA thereby interfering with replication and transcription of bacteria. As a competitive inhibitor of para-aminobenzoic acid (PABA), sulfadiazine inhibits bacterial dihydropteroate synthase, thereby resulting in disruption of folic acid metabolism and ultimately DNA synthesis. Silver sulfadiazine is only found in individuals that have used or taken this drug. It is a sulfa derivative topical antibacterial used primarily on second- and third-degree burns. [Wikipedia] Studies utilizing radioactive micronized silver sulfadiazine, electron microscopy, and biochemical techniques have revealed that the mechanism of action of silver sulfadiazine on bacteria differs from silver nitrate and sodium sulfadiazine. Silver sulfadiazine acts only on the cell membrane and cell wall to produce its bactericidal effect. A specific mechanism of action has not been determined, but silver sulfadiazine's effectiveness may possibly be from a synergistic interaction, or the action of each component. Silver is a biocide, which binds to a broad range of targets. Silver ions bind to nucleophilic amino acids, as well as sulfhydryl, amino, imidazole, phosphate, and carboxyl groups in proteins, causing protein denaturation and enzyme inhibition. Silver binds to surface membranes and proteins, causing proton leaks in the membrane, leading to cell death. Sulfadiazine is a competitive inhibitor of bacterial para-aminobenzoic acid (PABA), a substrate of the enzyme dihydropteroate synthetase. The inhibited reaction is necessary in these organisms for the synthesis of folic acid. Antibacterial used topically in burn therapy. See also: Sulfadiazine (has active moiety); Silver cation (has active moiety); Enrofloxacin; Silver sulfadiazine (component of). Drug Indication Indicated as an adjunct for the prevention and treatment of wound sepsis in patients with second- and third-degree burns. Mechanism of Action Studies utilizing radioactive micronized silver sulfadiazine, electron microscopy, and biochemical techniques have revealed that the mechanism of action of silver sulfadiazine on bacteria differs from silver nitrate and sodium sulfadiazine. Silver sulfadiazine acts only on the cell membrane and cell wall to produce its bactericidal effect. A specific mechanism of action has not been determined, but silver sulfadiazine's effectiveness may possibly be from a synergistic interaction, or the action of each component. Silver is a biocide, which binds to a broad range of targets. Silver ions bind to nucleophilic amino acids, as well as sulfhydryl, amino, imidazole, phosphate, and carboxyl groups in proteins, causing protein denaturation and enzyme inhibition. Silver binds to surface membranes and proteins, causing proton leaks in the membrane, leading to cell death. Sulfadiazine is a competitive inhibitor of bacterial para-aminobenzoic acid (PABA), a substrate of the enzyme dihydropteroate synthetase. The inhibited reaction is necessary in these organisms for the synthesis of folic acid. Pharmacodynamics Silver sulfadiazine has broad antimicrobial activity. It is bactericidal for many gram- negative and gram-positive bacteria as well as being effective against yeast. Silver sulfadiazine is not a carbonic anhydrase inhibitor and may be useful in situations where such agents are contraindicated.

Solubility Data

Solubility (In Vitro)

H2O : < 0.1 mg/mL DMSO : < 1 mg/mL

Solubility (In Vivo)

Note: Listed below are some common formulations that may be used to formulate products with low water solubility (e.g. < 1 mg/mL), you may test these formulations using a minute amount of products to avoid loss of samples. Injection Formulations (e.g. IP/IV/IM/SC) Injection Formulation 1: DMSO : Tween 80： Saline = 10 : 5 : 85 (i.e. 100 μL DMSO stock solution → 50 μL Tween 80 → 850 μL Saline) *Preparation of saline: Dissolve 0.9 g of sodium chloride in 100 mL ddH ₂ O to obtain a clear solution. Injection Formulation 2: DMSO : PEG300 ：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL DMSO → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Injection Formulation 3: DMSO : Corn oil = 10 : 90 (i.e. 100 μL DMSO → 900 μL Corn oil) Example: Take the Injection Formulation 3 (DMSO : Corn oil = 10 : 90) as an example, if 1 mL of 2.5 mg/mL working solution is to be prepared, you can take 100 μL 25 mg/mL DMSO stock solution and add to 900 μL corn oil, mix well to obtain a clear or suspension solution (2.5 mg/mL, ready for use in animals). Injection Formulation 4: DMSO : 20% SBE-β-CD in saline = 10 : 90 [i.e. 100 μL DMSO → 900 μL (20% SBE-β-CD in saline)] *Preparation of 20% SBE-β-CD in Saline (4°C，1 week): Dissolve 2 g SBE-β-CD in 10 mL saline to obtain a clear solution. Injection Formulation 5: 2-Hydroxypropyl-β-cyclodextrin : Saline = 50 : 50 (i.e. 500 μL 2-Hydroxypropyl-β-cyclodextrin → 500 μL Saline) Injection Formulation 6: DMSO : PEG300 : castor oil : Saline = 5 : 10 : 20 : 65 (i.e. 50 μL DMSO → 100 μLPEG300 → 200 μL castor oil → 650 μL Saline) Injection Formulation 7: Ethanol : Cremophor : Saline = 10： 10 : 80 (i.e. 100 μL Ethanol → 100 μL Cremophor → 800 μL Saline) Injection Formulation 8: Dissolve in Cremophor/Ethanol (50 : 50), then diluted by Saline Injection Formulation 9: EtOH : Corn oil = 10 : 90 (i.e. 100 μL EtOH → 900 μL Corn oil) Injection Formulation 10: EtOH : PEG300：Tween 80 : Saline = 10 : 40 : 5 : 45 (i.e. 100 μL EtOH → 400 μLPEG300 → 50 μL Tween 80 → 450 μL Saline) Oral Formulations Oral Formulation 1: Suspend in 0.5% CMC Na (carboxymethylcellulose sodium) Oral Formulation 2: Suspend in 0.5% Carboxymethyl cellulose Example: Take the Oral Formulation 1 (Suspend in 0.5% CMC Na) as an example, if 100 mL of 2.5 mg/mL working solution is to be prepared, you can first prepare 0.5% CMC Na solution by measuring 0.5 g CMC Na and dissolve it in 100 mL ddH2O to obtain a clear solution; then add 250 mg of the product to 100 mL 0.5% CMC Na solution, to make the suspension solution (2.5 mg/mL, ready for use in animals). Oral Formulation 3: Dissolved in PEG400 Oral Formulation 4: Suspend in 0.2% Carboxymethyl cellulose Oral Formulation 5: Dissolve in 0.25% Tween 80 and 0.5% Carboxymethyl cellulose Oral Formulation 6: Mixing with food powders Note: Please be aware that the above formulations are for reference only. InvivoChem strongly recommends customers to read literature methods/protocols carefully before determining which formulation you should use for in vivo studies, as different compounds have different solubility properties and have to be formulated differently.  (Please use freshly prepared in vivo formulations for optimal results.)

Preparing Stock Solutions		1 mg	5 mg	10 mg
	1 mM	2.8000 mL	14.0001 mL	28.0002 mL
	5 mM	0.5600 mL	2.8000 mL	5.6000 mL
	10 mM	0.2800 mL	1.4000 mL	2.8000 mL

*Note: Please select an appropriate solvent for the preparation of stock solution based on your experiment needs. For most products, DMSO can be used for preparing stock solutions (e.g. 5 mM, 10 mM, or 20 mM concentration); some products with high aqueous solubility may be dissolved in water directly. Solubility information is available at the above Solubility Data section. Once the stock solution is prepared, aliquot it to routine usage volumes and store at -20°C or -80°C. Avoid repeated freeze and thaw cycles.