Gallium nitrate (brand name Ganite) is the

gallium Gallium is a chemical element with the symbol Ga and atomic number 31. Discovered by French chemist Paul-Émile Lecoq de Boisbaudran in 1875, Gallium is in group 13 of the periodic table and is similar to the other metals of the group (aluminiu ...

salt Salt is a mineral composed primarily of sodium chloride (NaCl), a chemical compound belonging to the larger class of salts; salt in the form of a natural crystalline mineral is known as rock salt or halite. Salt is present in vast quantitie ...

nitric acid Nitric acid is the inorganic compound with the formula . It is a highly corrosive mineral acid. The compound is colorless, but older samples tend to be yellow cast due to decomposition into oxides of nitrogen. Most commercially available nitri ...

with the

chemical formula In chemistry, a chemical formula is a way of presenting information about the chemical proportions of atoms that constitute a particular chemical compound or molecule, using chemical element symbols, numbers, and sometimes also other symbols, ...

Ga(NO₃)₃. It is a drug used to treat symptomatic

hypercalcemia Hypercalcemia, also spelled hypercalcaemia, is a high calcium (Ca2+) level in the blood serum. The normal range is 2.1–2.6 mmol/L (8.8–10.7 mg/dL, 4.3–5.2 mEq/L), with levels greater than 2.6 mmol/L defined as hypercalcemi ...

secondary to cancer. It works by preventing the breakdown of bone through the inhibition of

osteoclast An osteoclast () is a type of bone cell that breaks down bone tissue. This function is critical in the maintenance, repair, and remodeling of bones of the vertebral skeleton. The osteoclast disassembles and digests the composite of hydrated pro ...

activity, thus lowering the amount of free

calcium Calcium is a chemical element with the symbol Ca and atomic number 20. As an alkaline earth metal, calcium is a reactive metal that forms a dark oxide-nitride layer when exposed to air. Its physical and chemical properties are most similar to ...

in the blood.Gallium Nitrate monograph. Lexi-Comp Online, Lexi-Drugs Online, Lexi-Comp Inc. Hudson, OH. Available at

. Accessed September 13th, 2008. Gallium nitrate is also used to synthesize other gallium compounds.

History

Gallium Gallium is a chemical element with the symbol Ga and atomic number 31. Discovered by French chemist Paul-Émile Lecoq de Boisbaudran in 1875, Gallium is in group 13 of the periodic table and is similar to the other metals of the group (aluminiu ...

(Ga) was discovered in 1875 by P.É. Lecoq de Boisbaudran. In most of its compounds, gallium is found with an oxidation number of 3+. Gallium chemically behaves similarly to

iron Iron () is a chemical element with symbol Fe (from la, ferrum) and atomic number 26. It is a metal that belongs to the first transition series and group 8 of the periodic table. It is, by mass, the most common element on Earth, right in f ...

3+ when forming a

coordination complex A coordination complex consists of a central atom or ion, which is usually metallic and is called the ''coordination centre'', and a surrounding array of bound molecules or ions, that are in turn known as ''ligands'' or complexing agents. Many ...

. That means gallium(III) and iron(III) are similar in similar

coordination number In chemistry, crystallography, and materials science, the coordination number, also called ligancy, of a central atom in a molecule or crystal is the number of atoms, molecules or ions bonded to it. The ion/molecule/atom surrounding the central i ...

, electrical charge, ion diameter and

electron configuration In atomic physics and quantum chemistry, the electron configuration is the distribution of electrons of an atom or molecule (or other physical structure) in atomic or molecular orbitals. For example, the electron configuration of the neon atom ...

Biological activity

Gallium atoms are bound to the phosphates of DNA at low gallium concentrations, forming a stable complex. Gallium competes with

magnesium Magnesium is a chemical element with the symbol Mg and atomic number 12. It is a shiny gray metal having a low density, low melting point and high chemical reactivity. Like the other alkaline earth metals (group 2 of the periodic ta ...

in DNA binding, since its DNA affinity is 100 times higher than that of magnesium. No interactions have been found between the metal and DNA bases. According to Hedley et al., gallium inhibits replicative DNA synthesis, the major gallium-specific target probably being

ribonucleotide reductase Ribonucleotide reductase (RNR), also known as ribonucleoside diphosphate reductase (rNDP), is an enzyme that catalyzes the formation of deoxyribonucleotides from ribonucleotides. It catalyzes this formation by removing the 2'-hydroxyl group of th ...

. In addition to that, it was reported by Chitambar that gallium binds to

transferrin Transferrins are glycoproteins found in vertebrates which bind to and consequently mediate the transport of iron (Fe) through blood plasma. They are produced in the liver and contain binding sites for two Fe3+ ions. Human transferrin is encode ...

more strongly than iron. The

complex Complex commonly refers to: * Complexity, the behaviour of a system whose components interact in multiple ways so possible interactions are difficult to describe ** Complex system, a system composed of many components which may interact with each ...

inhibits DNA synthesis by acting on the M2 subunit of ribonucleotide reductase. Gallium(III) seems to act as an antagonist to the actions of several ions (Ca²⁺, Mg²⁺, Fe²⁺ and Zn²⁺) in processes of

cellular metabolism Metabolism (, from el, μεταβολή ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cell ...

. The action of gallium on bone metabolism decreases

associated with cancer. However, gallium is mostly found within the cell as a salt in

lysosome A lysosome () is a membrane-bound organelle found in many animal cells. They are spherical vesicles that contain hydrolytic enzymes that can break down many kinds of biomolecules. A lysosome has a specific composition, of both its membrane prot ...

Preparation

Gallium nitrate is commercially available as the hydrate. The nonahydrate may also be prepared by dissolving gallium in nitric acid, followed by recrystallization. The structure of gallium nitrate nonahydrate has been determined by X-ray crystallography.

Use and manufacturing

Preparation of gallium nitride from gallium nitrate

GaN powder was synthesized using a direct current (DC) non-transferred arc plasma. Kim, Tae-Hee, Sooseok Choi, and Dong-Wha Park. "Thermal plasma synthesis of crystalline gallium nitride nanopowder from gallium nitrate hydrate and melamine." ''Nanomaterials'' 6.3 (2016): 38.

Medication Information

Gallium nitrate injection is a clear, colorless, odorless, sterile solution of gallium nitrate, a hydrated

nitrate Nitrate is a polyatomic ion A polyatomic ion, also known as a molecular ion, is a covalent bonded set of two or more atoms, or of a metal complex, that can be considered to behave as a single unit and that has a net charge that is not zer ...

salt of the group IIIa element, gallium. The stable, nonahydrate, Ga(NO₃)₃•9H2O is a white, slightly hygroscopic, crystalline powder of molecular weight 417.87, that is readily soluble in water. Each mL of Ganite (gallium nitrate injection) contains gallium nitrate 25 mg (on an anhydrous basis) and sodium citrate dihydrate 28.75 mg. The solution may contain

sodium hydroxide Sodium hydroxide, also known as lye and caustic soda, is an inorganic compound with the formula NaOH. It is a white solid ionic compound consisting of sodium cations and hydroxide anions . Sodium hydroxide is a highly caustic base and alkali ...

hydrochloric acid Hydrochloric acid, also known as muriatic acid, is an aqueous solution of hydrogen chloride. It is a colorless solution with a distinctive pungent smell. It is classified as a strong acid Acid strength is the tendency of an acid, symbol ...

for pH adjustment to 6.0-7.0.Gallium Nitrate
National Center for Biotechnology Information, U.S. National Library of Medicine. April 13th, 2012

Overdose

Use of higher doses of gallium nitrate than recommended may cause

nausea Nausea is a diffuse sensation of unease and discomfort, sometimes perceived as an urge to vomit. While not painful, it can be a debilitating symptom if prolonged and has been described as placing discomfort on the chest, abdomen, or back of the ...

, vomiting and increases risk of

chronic kidney disease Chronic kidney disease (CKD) is a type of kidney disease in which a gradual loss of kidney function occurs over a period of months to years. Initially generally no symptoms are seen, but later symptoms may include leg swelling, feeling tired, vo ...

. In the case of overdose,

serum calcium Calcium ions (Ca2+) contribute to the physiology and biochemistry of organisms' cells. They play an important role in signal transduction pathways, where they act as a second messenger, in neurotransmitter release from neurons, in contraction of ...

should be monitored, patients should receive vigorous hydration for 2–3 days and any further drug administrations should be discontinued.

Treatment

The action of gallium in gallium nitrate on bone

metabolism Metabolism (, from el, μεταβολή ''metabolē'', "change") is the set of life-sustaining chemical reactions in organisms. The three main functions of metabolism are: the conversion of the energy in food to energy available to run cell ...

decreases the hypercalcemia associated with cancer. Gallium inhibits osteoclastic activity and therefore decreases

hydroxyapatite Hydroxyapatite, also called hydroxylapatite (HA), is a naturally occurring mineral form of calcium apatite with the formula Ca5(PO4)3(OH), but it is usually written Ca10(PO4)6(OH)2 to denote that the crystal unit cell comprises two entities. ...

crystal formation, with adsorption of gallium onto the surfaces of

crystals. Also, the increased concentration of gallium in the bone leads to increasing the synthesis of

collagen Collagen () is the main structural protein in the extracellular matrix found in the body's various connective tissues. As the main component of connective tissue, it is the most abundant protein in mammals, making up from 25% to 35% of the whole ...

as well as the formation of the

bone tissue A bone is a rigid organ that constitutes part of the skeleton in most vertebrate animals. Bones protect the various other organs of the body, produce red and white blood cells, store minerals, provide structure and support for the body, an ...

inside the cell. It has been reported that a protracted infusion was effective against cancer-associated hypercalcemia. Preliminary studies in

bladder carcinoma Bladder cancer is any of several types of cancer arising from the tissues of the urinary bladder. Symptoms include blood in the urine, pain with urination, and low back pain. It is caused when epithelial cells that line the bladder become mali ...

carcinoma Carcinoma is a malignancy that develops from epithelial cells. Specifically, a carcinoma is a cancer that begins in a tissue that lines the inner or outer surfaces of the body, and that arises from cells originating in the endodermal, mesodermal ...

of the urothelium and

lymphomas Lymphoma is a group of blood and lymph tumors that develop from lymphocytes (a type of white blood cell). In current usage the name usually refers to just the cancerous versions rather than all such tumours. Signs and symptoms may include enlar ...

are also promising. Another interesting schedule of subcutaneous injection with low doses of gallium nitrate has been proposed, especially for the treatment of bone

metastases Metastasis is a pathogenic agent's spread from an initial or primary site to a different or secondary site within the host's body; the term is typically used when referring to metastasis by a cancerous tumor. The newly pathological sites, then, ...

, but the definitive results have not yet been published.

Chemical Reactivity

Gallium nitrate can react with

reducing agents In chemistry, a reducing agent (also known as a reductant, reducer, or electron donor) is a chemical species that "donates" an electron to an (called the , , , or ). Examples of substances that are commonly reducing agents include the Earth meta ...

to generate heat and products that may be gaseous. The products may themselves be capable of further reactions (such as combustion in the air). The

chemical reduction Redox (reduction–oxidation, , ) is a type of chemical reaction in which the oxidation states of substrate change. Oxidation is the loss of electrons or an increase in the oxidation state, while reduction is the gain of electrons or a d ...

of materials in this group can be rapid, but often requires initiation of heat,

catalyst Catalysis () is the process of increasing the rate of a chemical reaction by adding a substance known as a catalyst (). Catalysts are not consumed in the reaction and remain unchanged after it. If the reaction is rapid and the catalyst recyc ...

and addition of a solvent. Explosive mixtures of gallium nitrate with reducing agents often persist unchanged for long periods if initiation is prevented. Some inorganic oxidizing agents such as gallium nitrate are salts of metals that are soluble in water; dissolution dilutes but does not nullify the oxidizing power of such materials. Generally, inorganic oxidizing agents can react violently with active metals,

cyanides Cyanide is a naturally occurring, rapidly acting, toxic chemical that can exist in many different forms. In chemistry, a cyanide () is a chemical compound that contains a functional group. This group, known as the cyano group, consists of a ...

esters In chemistry, an ester is a compound derived from an oxoacid (organic or inorganic) in which at least one hydroxyl group () is replaced by an alkoxy group (), as in the substitution reaction of a carboxylic acid and an alcohol. Glycerides are ...

, and

thiocyanates Thiocyanate (also known as rhodanide) is the anion . It is the conjugate base of thiocyanic acid. Common derivatives include the colourless salts potassium thiocyanate and sodium thiocyanate. Mercury(II) thiocyanate was formerly used in pyrot ...

Adverse Reaction

Kidney

Adverse renal effects have been reported in about 12.5% of patients treated with gallium nitrate. Two patients receiving gallium nitrate and one patient receiving

calcitonin Calcitonin is a 32 amino acid peptide hormone secreted by parafollicular cells (also known as C cells) of the thyroid (or endostyle) in humans and other chordates. in the ultimopharyngeal body. It acts to reduce blood calcium (Ca2+), opposing the ...

developed acute

renal failure Kidney failure, also known as end-stage kidney disease, is a medical condition in which the kidneys can no longer adequately filter waste products from the blood, functioning at less than 15% of normal levels. Kidney failure is classified as eit ...

in a controlled trial of patients with cancer-related hypercalcemia. Also, it was reported that gallium nitrate should not be administered to patients with

serum creatinine Creatinine (; ) is a breakdown product of creatine phosphate from muscle and protein metabolism. It is released at a constant rate by the body (depending on muscle mass). Biological relevance Serum creatinine (a blood measurement) is an import ...

>2.5 mg/dL.

Blood Pressure

In a controlled trial of patients, it was noticed a decrease in mean

systolic Systole ( ) is the part of the cardiac cycle during which some chambers of the heart contract after refilling with blood. The term originates, via New Latin, from Ancient Greek (''sustolē''), from (''sustéllein'' 'to contract'; from ''sun ...

and

diastolic Diastole ( ) is the relaxed phase of the cardiac cycle when the chambers of the heart are re-filling with blood. The contrasting phase is systole when the heart chambers are contracting. Atrial diastole is the relaxing of the atria, and ventricu ...

blood pressure after the treatment with gallium nitrate. The decrease in

blood pressure Blood pressure (BP) is the pressure of circulating blood against the walls of blood vessels. Most of this pressure results from the heart pumping blood through the circulatory system. When used without qualification, the term "blood pressure" r ...

was asymptomatic and did not require specific treatment.

Hematologic

High doses of gallium nitrate were associated with

anemia Anemia or anaemia (British English) is a blood disorder in which the blood has a reduced ability to carry oxygen due to a lower than normal number of red blood cells, or a reduction in the amount of hemoglobin. When anemia comes on slowly, th ...

when used in treating patients for advanced cancer. In results, several patients have received red blood cell

transfusions Blood transfusion is the process of transferring blood products into a person's circulation intravenously. Transfusions are used for various medical conditions to replace lost components of the blood. Early transfusions used whole blood, but mo ...

References

External links

Ganite
brand website {{nitrates Gallium compounds Nitrates