Zinc chloride targets multiple cellular proteins and enzymes. It has been associated with GPR39 (G-protein coupled receptor 39) as a target and acts as an agonist of aquaporin 1 (AQP1). Zinc ions serve as essential cofactors for hundreds of enzymes and transcription factors, playing critical roles in DNA synthesis, cell division, protein synthesis, and immune function. Zinc binds to zinc finger domains in transcription factors, regulating gene expression.

Zinc chloride provides essential zinc ions for cellular metabolism. In vitro, zinc has been shown to have significant cytotoxicity for tumor cells and to inhibit leukemia inhibitory factor, which may be due to its ability to bind copper ions. Zinc chloride has a potent rate constant for inhibition of hyperproliferative diseases such as cancer and HIV. It is used in cell culture media as a nutrient supplement to support cellular growth and function.

Zinc chloride is used in total parenteral nutrition to maintain zinc serum levels and prevent deficiency syndromes. Zinc can be used for the treatment and prevention of zinc deficiency and its consequences. In vivo, zinc is essential for normal growth, immune function, wound healing, and sensory function. It is distributed throughout the body, with highest concentrations in muscle, bone, skin, and liver.

In vitro receptor binding assays are performed using radiolabeled zinc or fluorescent zinc probes incubated with proteins or cell membranes expressing zinc-binding targets. Zinc binding affinity is measured by isothermal titration calorimetry (ITC) or surface plasmon resonance (SPR). Competition assays with chelating agents such as EDTA can be used to assess the specificity of zinc binding.

Cell culture media are supplemented with zinc chloride at specific concentrations (typically 0.5-5 μM) to support cellular growth and function. Cell lines are treated with zinc chloride at varying concentrations to assess cytotoxicity, proliferation, or zinc-dependent signaling. Cell viability is measured using standard assays such as MTT or CCK-8. Zinc-induced metallothionein expression can be measured by Western blotting or qPCR.

Animal models of zinc deficiency are used to assess the effects of zinc chloride supplementation. Rodents are administered zinc chloride via oral gavage or intravenous injection. Zinc levels in serum, tissues, and urine are measured by atomic absorption spectroscopy or inductively coupled plasma mass spectrometry (ICP-MS). Growth, immune function, and wound healing are assessed to evaluate zinc status.

Absorption, Distribution and Excretion
The oral bioavailability of zinc in humans is approximately 33%, but bioavailability varies depending on individual patient differences and current zinc levels. Further data on the pharmacokinetics of zinc chloride are unclear. Zinc is primarily excreted in feces. Gastrointestinal excretion accounts for approximately half of total zinc excretion. A study in healthy subjects found a zinc clearance rate of 0.63 ± 0.39 μg/min. In subjects receiving a low dose of zinc chloride (⁶⁵Z) and undergoing systemic measurements… the estimated absorption rate was 58% to 77% in 5 control subjects and 16% to 42% in 3 patients with enterohepatic acrodermatitis. Systemic zinc retention was measured over a 34-day period… one week after oral administration of a 2 μg tracer dose of zinc chloride to mice, the highest zinc concentration was observed in bone tissue, followed by the liver and kidneys.
In adult male rats, 95 hours after intravenous injection of carrier-free (65) zinc chloride, the systemic zinc retention was 78.3% of the dose.
In one study, 95 hours after injection of (65) zinc chloride in rats, 20.1% of the dose was recovered in feces, while only 0.6% was recovered in urine…
In mice, after intravenous injection of 0.3 μg of zinc chloride, approximately 50% of the total dose was recovered in feces within one week. In dogs, after intravenous injection of 6.5 μg of zinc chloride, approximately 20% of the zinc was recovered in feces within one week. During the same period, urinary excretion in both animals was well below 5% of the administered dose…In rats, after a single intravenous injection of 0.1 mg (65) zinc chloride, 4% of the zinc was excreted in bile within 48 hours.
For more data on the absorption, distribution, and excretion (complete) of zinc chloride (17 types), please visit the HSDB record page.

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Metabolism/Metabolites
Zinc chloride dissociates into ions in the body and is not further metabolized. Zinc can enter the body through the lungs, skin, and gastrointestinal tract. Intestinal absorption of zinc is regulated by the zinc carrier protein CRIP. Zinc also binds to metallothionein, helping to prevent excessive absorption. Zinc is widely distributed, present in all tissues and tissue fluids, with higher concentrations in the liver, gastrointestinal tract, kidneys, skin, lungs, brain, heart, and pancreas. In the blood, zinc binds to carbonic anhydrase in erythrocytes, as well as to albumin, β2-macroglobulin, and amino acids in plasma. Zinc bound to albumin and amino acids can diffuse across tissue membranes. Zinc is excreted in urine and feces. (L49)

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Biological Half-Life
Using a two-compartment model, the half-life of zinc is 4.5–26 days, with a second half-life of 387–478 days.
The systemic half-life of zinc is 162–500 days; [TDR, p. 1245]

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Zinc chloride is administered intravenously in total parenteral nutrition. Zinc is distributed throughout the body, bound primarily to albumin and α2-macroglobulin in plasma. It is excreted primarily in feces via biliary secretion and to a lesser extent in urine. The half-life of zinc in the body is approximately 2-3 weeks. Zinc homeostasis is regulated by intestinal absorption and endogenous excretion.

Protein Binding
70% of zinc in plasma is bound to proteins, and some is bound to serum albumin.

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Zinc chloride is generally safe at therapeutic doses. Acute toxicity can cause gastrointestinal irritation, nausea, and vomiting. Inhalation of zinc chloride fumes can cause respiratory irritation and metal fume fever. Chronic high-dose zinc supplementation can cause copper deficiency due to competition for absorption. The tolerable upper intake level for zinc in adults is 40 mg/day. Zinc chloride is corrosive and should be handled with appropriate PPE.

Zinc chloride is a white crystalline solid, readily soluble in water. It is corrosive to metals and therefore irritates the skin, eyes, and mucous membranes. It is used in wood preservation, as a flux, as a catalyst in metal chemistry and manufacturing, and for many other purposes. Zinc chloride solution is a colorless liquid, slightly corrosive to metals, and can burn the eyes, skin, and mucous membranes. Zinc chloride is an ionic solution suitable for total parenteral nutrition to maintain zinc levels and prevent zinc deficiency. Zinc chloride was approved by the U.S. Food and Drug Administration (FDA) prior to June 26, 1986. Zinc chloride is an ionic salt essential for the synthesis of cholesterol, proteins, and fats. Zinc plays a vital role in the normal functioning of the immune system. Zinc is necessary for the enzyme activity required for cell division, cell growth, and wound healing, as well as for the liver's release of vitamin A. Zinc plays a role in maintaining the sensitivity of smell and taste and is essential for maintaining prostate reproductive health and insulin function. Zinc is also involved in carbohydrate metabolism. Zinc chloride can be administered orally or parenterally as a nutritional supplement. Zinc chloride is a nutritional supplement. Several salts containing the tetrachlorozincate anion (ZnCl₂⁴⁻) are known. Coulter's reagent, V₂Cl₃(thf)₆Zn₂Cl₆, is one such salt containing Zn₂Cl₂⁴⁻. The compound Cs₃ZnCl₅ contains tetrahedral coordinated ZnCl₂⁴⁻ and Cl⁻ anions. No compounds containing ZnCl₄⁴⁻ ions have been found. Zinc chloride is known to have four polymorphs, in which Zn²⁺ ions are coordinated with four chloride ions in a trigonal-planar manner. Pure anhydrous orthorhombic zinc chloride rapidly transforms into other polymorphs upon exposure to air; one possible explanation is that the presence of OH groups promotes this rearrangement. Molten zinc chloride, upon rapid cooling, forms a glassy state, a rigid amorphous solid; this property is related to its melt structure. Zinc chloride belongs to the transition metal chloride family. In these inorganic compounds, the largest halogen atom is chlorine, and the heaviest metal atom is a transition metal. See also: Zinc cation (containing the active moiety); Benzocaine; Zinc chloride (component); Benzyl alcohol; Zinc chloride (component)... See more...

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Drug Indications
Zinc chloride injection is indicated for total parenteral nutrition to maintain serum zinc levels and prevent zinc deficiency.

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Mechanism of Action
Zinc plays a catalytic, structural, and regulatory role in the body. Zinc is a component of approximately 3000 human proteins. Zinc, through the action of metallothioneins, has a cytoprotective effect against reactive oxygen species-mediated apoptosis. In promyelocytic leukemia cell lines, zinc enhances the expression of A20 mRNA, which reduces NF-κB activation through the TRAF pathway, thereby reducing the gene expression and production of TNF-α, IL-1β, and IL-8. In patients with diarrhea, zinc can restore the integrity of the mucosal barrier, restore the activity of brush border enzymes in intestinal cells, promote antibody production, and promote the generation of circulating lymphocytes to fight intestinal pathogens. Zinc can also act as a potassium channel blocker, directly affecting ion channels and inhibiting cAMP-mediated chloride ion secretion. Zinc deficiency reduces thymosin levels, inhibits the maturation of helper T cells, and reduces the production of Th1 cytokines such as IL-2. Decreased IL-2 levels reduce the activity of NK cells and CD8+ T cells. Zinc deficiency also leads to reduced CD4+ T cell production, decreased NF-κB activation, decreased IκB phosphorylation levels, and reduced NF-κB binding to DNA.
Hepatocytes cultured in monolayers for 22 hours, followed by treatment with zinc chloride (100 μM) for 24 hours, showed a 15-fold increase in metallothionein (MT) concentration. Following zinc chloride pretreatment, hepatocytes were treated with 20 or 40 μM silver nitrate for 24 hours, and cytotoxicity was assessed by enzyme leakage and intracellular potassium loss. Silver toxicity was significantly reduced in zinc-pretreated cells. Furthermore, while zinc pretreatment did not significantly affect silver uptake by hepatocytes, it altered the subcellular distribution of silver, with greater accumulation in the cytosol and less accumulation in the nucleus, mitochondria, and microsomal components. In control cells, silver in the cytosol was primarily bound to high-molecular-weight proteins, while silver in zinc-pretreated cells was primarily bound to metallothionein (MT). In primary rat hepatocyte cultures, zinc-induced MT protected cells from silver-induced cytotoxicity, which is caused by silver binding to MT, leading to reduced metal content in key organelles and proteins.

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Zinc chloride is an inorganic compound used as a source of zinc ions in clinical nutrition and research. CAS: 7646-85-7. Molecular formula: ZnCl2, molecular weight: 136.30. Synonyms: dichlorozinc, zinc dichloride. It is available as a solution for injection and as a solid for research use. It is hygroscopic and should be stored in a tightly sealed container. For research and clinical use only.

133.866

7646-85-7

5727

White, very deliquesce granules, or fused pieces or rods
White, hygroscopic crystals
White particulate dispersed in air /Zinc chloride fume/

2.91g/cm3

219-220ºC at 10 mmHg

554 °F (NIOSH, 2024) ; 541 °F (USCG, 1999) ; Approximately 290 °C ; 290 °C ; 554 °F ; 290 °C ; 554 °F

732ºC

1 mm Hg ( 428 °C)

1.376

0

0

0

3

2.8

0

[Cl-].[Cl-].[Zn+2]

JIAARYAFYJHUJI-UHFFFAOYSA-L

InChI=1S/2ClH.Zn/h2*1H;/q;;+2/p-2

dichlorozinc

2934.99.9001

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 and light.

Room temperature (This product is stable at ambient temperature for a few days during ordinary shipping and time spent in Customs)

H2O :~100 mg/mL (~733.73 mM; with sonication)

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.

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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).

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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)

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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).

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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

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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.

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 (Please use freshly prepared in vivo formulations for optimal results.)