Gallium nitrate

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Gallium nitrate
Gallium nitrate nonanhydrate.jpg
Names
IUPAC name
Gallium trinitrate
Other names
Gallium(III) nitrate
Nitric acid, gallium salt
Identifiers
3D model (JSmol)
ChEMBL
DrugBank
ECHA InfoCard 100.033.453 OOjs UI icon edit-ltr-progressive.svg
EC Number
  • 236-815-5
PubChem CID
UNII
UN number 1477
  • InChI=1S/Ga.3NO3/c;3*2-1(3)4/q+3;3*-1
    Key: CHPZKNULDCNCBW-UHFFFAOYSA-N
  • [N+](=O)([O-])[O-].[N+](=O)([O-])[O-].[N+](=O)([O-])[O-].[Ga+3]
Properties
Ga(NO3)3
Molar mass 255.7377 g/mol
Hazards
GHS labelling:
GHS-pictogram-rondflam.svg GHS-pictogram-acid.svg GHS-pictogram-exclam.svg
Danger
H272, H314, H315, H319, H335
P210, P220, P221, P260, P261, P264, P271, P280, P301+P330+P331, P302+P352, P303+P361+P353, P304+P340, P305+P351+P338, P310, P312, P321, P332+P313, P337+P313, P362, P363, P370+P378, P403+P233, P405, P501
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
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Gallium nitrate (brand name Ganite) is the gallium salt of nitric acid with the chemical formula Ga(NO3)3. It is a drug used to treat symptomatic hypercalcemia secondary to cancer. It works by preventing the breakdown of bone through the inhibition of osteoclast activity, thus lowering the amount of free calcium in the blood. [1] [2] Gallium nitrate is also used to synthesize other gallium compounds.

Contents

History

Gallium (Ga) was discovered in 1875 by P.É. Lecoq de Boisbaudran. [3] In most of its compounds, gallium is found with an oxidation number of 3+. Gallium chemically behaves similarly to iron 3+ when forming a coordination complex. [4] That means gallium(III) and iron(III) are similar in similar coordination number, electrical charge, ion diameter and electron configuration.

Biological activity

Gallium atoms are bound to the phosphates of DNA at low gallium concentrations, forming a stable complex. [5] Gallium competes with magnesium 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. [6] According to Hedley et al., gallium inhibits replicative DNA synthesis, the major gallium-specific target probably being ribonucleotide reductase. [6] In addition to that, it was reported by Chitambar that gallium binds to transferrin more strongly than iron. The transferrin gallium complex inhibits DNA synthesis by acting on the M2 subunit of ribonucleotide reductase. [7] Gallium(III) seems to act as an antagonist to the actions of several ions (Ca2+, Mg2+, Fe2+ and Zn2+) in processes of cellular metabolism. The action of gallium on bone metabolism decreases hypercalcemia associated with cancer. However, gallium is mostly found within the cell as a salt in lysosomes.

Preparation

Gallium nitrate is commercially available as the hydrate. The nonahydrate may also be prepared by dissolving gallium in nitric acid, followed by recrystallization. [8] The structure of gallium nitrate nonahydrate has been determined by X-ray crystallography. [9]

Use and manufacturing

Preparation of gallium nitride from gallium nitrate

GaN powder was synthesized using a direct current (DC) non-transferred arc plasma. [10]

Medication Information

Gallium nitrate injection is a clear, colorless, odorless, sterile solution of gallium nitrate, a hydrated nitrate 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 or hydrochloric acid for pH adjustment to 6.0-7.0. [11]

Overdose

Use of higher doses of gallium nitrate than recommended may cause nausea, vomiting and increases risk of chronic kidney disease. In the case of overdose, serum calcium should be monitored, patients should receive vigorous hydration for 2–3 days and any further drug administrations should be discontinued. [11]

Treatment

The action of gallium in gallium nitrate on bone metabolism decreases the hypercalcemia associated with cancer. Gallium inhibits osteoclastic activity and therefore decreases hydroxyapatite crystal formation, with adsorption of gallium onto the surfaces of hydroxyapatite crystals. [12] Also, the increased concentration of gallium in the bone leads to increasing the synthesis of collagen as well as the formation of the bone tissue inside the cell. It has been reported that a protracted infusion was effective against cancer-associated hypercalcemia. [13] Preliminary studies in bladder carcinoma, carcinoma of the urothelium and lymphomas are also promising. [14] Another interesting schedule of subcutaneous injection with low doses of gallium nitrate has been proposed, especially for the treatment of bone metastases, but the definitive results have not yet been published. [15]

Chemical reactivity

Gallium nitrate can react with reducing agents 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 of materials in this group can be rapid, but often requires initiation of heat, catalyst 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, esters, and thiocyanates. [11]

Adverse reactions

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 developed acute renal failure 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 >2.5 mg/dL. [11]

Blood pressure

In a controlled trial of patients, it was noticed a decrease in mean systolic and diastolic blood pressure after the treatment with gallium nitrate. The decrease in blood pressure was asymptomatic and did not require specific treatment. [11]

Hematologic

High doses of gallium nitrate were associated with anemia when used in treating patients for advanced cancer. In results, several patients have received red blood cell transfusions. [11]

See also

Related Research Articles

<span class="mw-page-title-main">Gallium</span> Chemical element, symbol Ga and atomic number 31

Gallium is a chemical element with the symbol Ga and atomic number 31. Discovered by the 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.

<span class="mw-page-title-main">Magnesium</span> Chemical element, symbol Mg and atomic number 12

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 it occurs naturally only in combination with other elements and it almost always has an oxidation state of +2. It reacts readily with air to form a thin passivation coating of magnesium oxide that inhibits further corrosion of the metal. The free metal burns with a brilliant-white light. The metal is obtained mainly by electrolysis of magnesium salts obtained from brine. It is less dense than aluminium and is used primarily as a component in strong and lightweight alloys that contain aluminium.

<span class="mw-page-title-main">Magnesium sulfate</span> Chemical compound with formula MgSO4

Magnesium sulfate or magnesium sulphate (in English-speaking countries other than the US) is a chemical compound, a salt with the formula MgSO4, consisting of magnesium cations Mg2+ (20.19% by mass) and sulfate anions SO2−4. It is a white crystalline solid, soluble in water but not in ethanol.

<span class="mw-page-title-main">Magnesium in biology</span> Use of Magnesium by organisms

Magnesium is an essential element in biological systems. Magnesium occurs typically as the Mg2+ ion. It is an essential mineral nutrient (i.e., element) for life and is present in every cell type in every organism. For example, adenosine triphosphate (ATP), the main source of energy in cells, must bind to a magnesium ion in order to be biologically active. What is called ATP is often actually Mg-ATP. As such, magnesium plays a role in the stability of all polyphosphate compounds in the cells, including those associated with the synthesis of DNA and RNA.

<span class="mw-page-title-main">Parathyroid hormone</span> Mammalian protein found in Homo sapiens

Parathyroid hormone (PTH), also called parathormone or parathyrin, is a peptide hormone secreted by the parathyroid glands that regulates the serum calcium concentration through its effects on bone, kidney, and intestine.

<span class="mw-page-title-main">Calcitonin</span> Amino acid peptide hormone secreted by the thyroid gland

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 effects of parathyroid hormone (PTH).

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 hypercalcemia. Those with a mild increase that has developed slowly typically have no symptoms. In those with greater levels or rapid onset, symptoms may include abdominal pain, bone pain, confusion, depression, weakness, kidney stones or an abnormal heart rhythm including cardiac arrest.

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<span class="mw-page-title-main">Tetrafluoroborate</span> Anion

Tetrafluoroborate is the anion BF
4
. This tetrahedral species is isoelectronic with tetrafluoroberyllate (BeF2−
4
), tetrafluoromethane (CF4), and tetrafluoroammonium (NF+
4
) and is valence isoelectronic with many stable and important species including the perchlorate anion, ClO
4
, which is used in similar ways in the laboratory. It arises by the reaction of fluoride salts with the Lewis acid BF3, treatment of tetrafluoroboric acid with base, or by treatment of boric acid with hydrofluoric acid.

A gallium scan is a type of nuclear medicine test that uses either a gallium-67 (67Ga) or gallium-68 (68Ga) radiopharmaceutical to obtain images of a specific type of tissue, or disease state of tissue. Gallium salts like gallium citrate and gallium nitrate may be used. The form of salt is not important, since it is the freely dissolved gallium ion Ga3+ which is active. Both 67Ga and 68Ga salts have similar uptake mechanisms. Gallium can also be used in other forms, for example 68Ga-PSMA is used for cancer imaging. The gamma emission of gallium-67 is imaged by a gamma camera, while the positron emission of gallium-68 is imaged by positron emission tomography (PET).

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<span class="mw-page-title-main">Cerium nitrates</span> Chemical compound

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References

  1. Gallium Nitrate monograph. Lexi-Comp Online, Lexi-Drugs Online, Lexi-Comp Inc. Hudson, OH. Available at: Archived 2004-11-16 at the Wayback Machine . Accessed September 13th, 2008.
  2. Ganite at drugs.com
  3. Green, MA; Welch, MJ (1989). "Gallium radiopharmaceutical chemistry". Int J Rad Appl Instrum B. 16 (5): 435–448. doi:10.1016/0883-2897(89)90053-6. PMID   2681083.
  4. Hart, MM; Adamson, RH (1971). "Antitumor activity and toxicity of salts of inorganic group 3a metals: aluminum, gallium, indium, and thallium". Proc Natl Acad Sci USA. 68 (7): 1623–1626. Bibcode:1971PNAS...68.1623H. doi: 10.1073/pnas.68.7.1623 . PMC   389254 . PMID   5283954.
  5. Hart, MM; Smith, CF; Yancey, ST; Adamson, RH (1971). "Toxicity and antitumor activity of gallium nitrate and periodically related metal salts". J Natl Cancer Inst. 47 (5): 1121–1127. PMID   4330799.
  6. 1 2 Manfait, M; Collery, P (1984). "Etude in vitro par spectroscopie Raman de la conformation d'un ADN sous l'influence des ions magnésium et gallium". Magnesium Bull. 4: 153–155.
  7. Hedley, DW; Tripp, EH; Slowiaczek, P; Mann, GJ (1988). "Effect of gallium on DNA synthesis by human T-cell lymphoblasts". Cancer Res. 48 (11): 3014–3018. PMID   3259158.
  8. Birnara, Christiana; Kessler, Vadim G.; Papaefstathiou, Giannis S. (2009). "Mononuclear gallium(III) complexes based on salicylaldoximes: Synthesis, structure and spectroscopic characterization". Polyhedron . 28 (15): 3291. doi:10.1016/j.poly.2009.04.039.
  9. Hendsbee, Arthur; Pye, Cory; Masuda, Jason (2009). "Hexaaquagallium(III) trinitrate trihydrate". Acta Crystallographica E . 65 (8): i65. doi:10.1107/S1600536809028086. PMC   2977161 . PMID   21583299.
  10. 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.
  11. 1 2 3 4 5 6 Gallium Nitrate. National Center for Biotechnology Information, U.S. National Library of Medicine. April 13th, 2012
  12. Warrell, RP Jr; Issacs, M; Alcock, NW; Bockman, RS (1987). "Gallium nitrate for treatment of refractory hypercalcemia from parathyroid carcinoma". Ann Intern Med. 107 (5): 683–686. doi:10.7326/0003-4819-107-5-683. PMID   2821862.
  13. Warrell, RP Jr (1988). "Questions about clinical trials in hypercalcemia [editorial]". J Clin Oncol. 6 (5): 759–761. doi:10.1200/jco.1988.6.5.759. PMID   3284973.
  14. Seligman, PA; Crawford, ED (1991). "Treatment of advanced transitional cell carcinoma of the bladder with continuousinfusion gallium nitrate". J Natl Cancer Inst. 83 (21): 1582–1584. doi:10.1093/jnci/83.21.1582. PMID   1960756.
  15. Warrell, RP Jr (1997). "Gallium nitrate for the treatment of bone metastases". Cancer. 80 (8 Suppl): 1680–1685. doi: 10.1002/(sici)1097-0142(19971015)80:8+<1680::aid-cncr19>3.0.co;2-w . PMID   9362436.
HNO3 He
LiNO3 Be(NO3)2 B(NO3)4 RONO2 NO3
NH4NO3
HOONO2 FNO3 Ne
NaNO3 Mg(NO3)2 Al(NO3)3
Al(NO3)4
SiPS ClONO2 Ar
KNO3 Ca(NO3)2 Sc(NO3)3 Ti(NO3)4 VO(NO3)3 Cr(NO3)3 Mn(NO3)2 Fe(NO3)2
Fe(NO3)3
Co(NO3)2
Co(NO3)3
Ni(NO3)2 CuNO3
Cu(NO3)2
Zn(NO3)2 Ga(NO3)3 GeAsSe BrNO3 Kr
RbNO3 Sr(NO3)2 Y(NO3)3 Zr(NO3)4 NbO(NO3)3 MoO2(NO3)2 Tc Ru(NO3)3 Rh(NO3)3 Pd(NO3)2
Pd(NO3)4
AgNO3
Ag(NO3)2
Cd(NO3)2 In(NO3)3 Sn(NO3)4 Sb(NO3)3 Te INO3 Xe(NO3)2
CsNO3 Ba(NO3)2   Lu(NO3)3 Hf(NO3)4 TaO(NO3)3 WO2(NO3)2 ReO3NO3 Os Ir3O(NO3)10 Pt(NO3)2
Pt(NO3)4
Au(NO3)3 Hg2(NO3)2
Hg(NO3)2
TlNO3
Tl(NO3)3
Pb(NO3)2 Bi(NO3)3
BiO(NO3)
Po(NO3)4 AtRn
FrNO3 Ra(NO3)2  LrRfDbSgBhHsMtDsRgCnNhFlMcLvTsOg
La(NO3)3 Ce(NO3)3
Ce(NO3)4
Pr(NO3)3 Nd(NO3)3 Pm(NO3)3 Sm(NO3)3 Eu(NO3)3 Gd(NO3)3 Tb(NO3)3 Dy(NO3)3 Ho(NO3)3 Er(NO3)3 Tm(NO3)3 Yb(NO3)3
Ac(NO3)3 Th(NO3)4 PaO2(NO3)3 UO2(NO3)2 Np(NO3)4 Pu(NO3)4 Am(NO3)3 Cm(NO3)3 Bk(NO3)3 Cf(NO3)3 EsFmMdNo