15663-27-1 Usage
Uses
Used in Anticancer Applications:
Cisplatin is used as an antineoplastic agent for the treatment of various cancer types, including non-Hodgkin's lymphoma, bladder cancer, ovarian cancer, testicular cancer, and cancers of the head and neck. It is particularly effective against solid tumors, such as those in the testes, ovaries, lungs, and other organs. Cisplatin is also used in combination therapy to enhance the efficacy of conventional chemotherapeutic drugs and improve chemo-sensitivity in resistant cases.
Used in Muscle Relaxation (Skeletal):
Cisplatin is used as a muscle relaxant, particularly in the treatment of skeletal muscle-related conditions.
Used in Antitumor Applications:
Cisplatin is employed as an antitumor agent, demonstrating its effectiveness in halting the cell cycle at the G2/M phase in vitro and showing activity against murine tumors transplanted into mice and in mouse xenograft models.
Used in Drug Delivery Systems:
Formulations containing cisplatin have been used in various drug delivery systems, such as liposomal forms and injectable collagen matrix gels, to improve its delivery, bioavailability, and therapeutic outcomes in the treatment of a wide variety of cancers.
Used in Inhibiting RecA Recombinase of M. tuberculosis:
Cisplatin also inhibits the RecA recombinase of M. tuberculosis (IC50 = 2 μM), blocking protein splicing and cell growth, which can be beneficial in the treatment of tuberculosis.
History of discovery
Cisplatin is currently one of the most commonly used drugs used in combination chemotherapy with its chemical full name being cis-dichlorodiamineplatinum. It belongs to inorganic metal complexes. After the dissociation of the chlorine atom, it can be cross-linked with the DNA of the cancer cell DNA, thereby destroying the DNA function. It can form intra-strand or inter-strand crosslink with the DNA and may also form a cross-link with DNA and protein, and can inhibit cell mitosis, belonging to cell cycle non-specific drugs. In addition to its anti-cancer effect, it is still capable of inhibiting lymphocyte transformation and having immunosuppression effect and thus can be used as the metal complex-class anti-cancer drugs.
In 1844, it had been first successfully developed by the French chemist Mario Rampini and has been ever called Rampini's salt. It appears as an orange crystal. It has a small solubility (being 0.252 g/ 100 g of water at 25 ℃) and can be produced through the reaction between tetrachloro platinum (II) solution of potassium and ammonia.
In 1891, the modern founder of coordination chemistry, Werner, starting from the study of this class of compounds, had successfully established a complex theory, and clarified the cis structure of the Rampini's salt.
It was not until 1965 that the anticancer activity of cisplatin was found by Rosenberg and his colleagues from University of Michigan USA. When studying the effect of the electric filed on the growth of E. coli, they found that when putting into the metallic platinum to the medium containing ammonium chloride and then sending through 2 ampere for two hours, the reproduction of E. coli was inhibited.
Further studies had showed that this is the effect of the cisplatin which is the product produced through the chemical reaction between the ammonia chloride and the platinum ion produced by electrolytic oxidation in the electrode. Rosenberg thought that given that cisplatin can prevent cell division, it should also have anticancer activity. Through the anti-cancer test, it has been proven that there is a good anti-cancer effect of cisplatin, drawing broad interest in metal complexes pharmacology. People had organized international cooperation research on chemistry, biology and medical field, finally enabling the successful applications of cisplatin in the treatment of cancer.
In December 1978, the US Food and Drug Administration had approved cisplatin for clinical application and make it as a commodity to supply the market. It has properties such as broad anti-tumor spectrum and being effective in treating hypoxic cells. However, it has toxicity to the kidneys, nervous system and pancreas. Modern pharmacology has classified this product as antineoplastic agents.
Pharmacological effects
Cisplatin is the most commonly used metal platinum complexes with the platinum atoms containing in the molecule being important for its anti tumor effect. However, it is also effective in the form of cis while being invalid in the Trans form. It can be cross-linked to DNA strand, showing cytotoxicity. After its dissolution inside the human body, it doesn’t need carrier transport in the body while being able to penetrate through the charged cell membrane. Owing to the low intracellular chloride concentration (4mmol /L), chloride ions are replaced by the water with the charge being positive which has a similar effect as bifunctional group of alkylating agent. It can combine with the nuclear DNA bases, forming three forms of cross-linking, resulting in DNA damage, further destroying DNA replication and transcription with the capability of inhibiting the synthesis of RNA and proteins at high concentrations as well. Cisplatin is characterized by broad anti-cancer spectrum, being effective in treating hypoxic cells and strong action. It has been widely used in the treatment of testicular cancer, ovarian cancer, uterine cancer, bladder cancer, cervical cancer, prostate cancer and brain cancer with significant efficacy. However, cisplatin has certain toxicity when being used in the treatment of cancer and thus being able to cause side effects. Therefore, it is necessary to continuously identify analogues of cisplatin with less toxicity and clinical effect being similar as cisplatin. So far scientists from various countries have been synthesized and tested thousands of cisplatin-related metal complexes and have developed the second-generation anti-cancer platinum complexes with carboplatin being the representative. The third generation anticancer metal complexes have also been identified with titanocene dichloride as the representative. These compounds have nothing to do with cisplatin from the chemical perspective but they have relative good efficacy in treating some kinds of cancer which can be hardly treated by cisplatin without doing harm to the kidney function. Now people in this area are continuing extensive research with the efforts majorly lining in exploring the anticancer mechanism of metal complexes at the molecular level. China has already started producing the goods of cisplatin and has carried out research in this area.
Cisplatin belongs to non-specific cell cycle drugs with cytotoxicity. Since the proliferation and synthesis rate of cancer cells is more rapid than normal cells, the cancer cell is more sensitive than normal cell to the toxic effects of this product. It can inhibit the DNA replication of cancer cell, and destroy the structure of the cell membrane. It has a strong broad-spectrum anti-cancer effect. It can be used for the treatment of ovarian cancer, prostate cancer, testicular cancer and other genitourinary malignancies with an excellent efficacy. When being used in combination with vincristine, cyclophosphamide and 5-fluorouracil, it has an excellent efficacy in the treatment of malignant lymphoma, breast cancer, carcinoma of head and neck squamous cell, thyroid cancer, and osteosarcoma, etc. Cisplatin, in combination with radiotherapy, can be used in the treatment for patients with advanced non-small cell lung cancer; nasopharyngeal cancer and esophageal cancer with prominent effect. It also has certain efficacy in the treatment of liver cancer and soft tissue sarcoma. Cisplatin, as a strong accumulative drug, is easy to produce renal toxicity with the gastrointestinal reactions being relatively common with neutropenia occurring in some patients but can be restored after the withdrawal of drugs for 7 to 14 days.
In addition, the DNA damage effect of this product can also possibly change the antigenicity in the nucleus or the cell surface so that the original hidden surface antigen is exposed, stimulating the immune suppression of antibodies and exert their cytotoxic effects. This information is edited by Xiongfeng Dai from lookchem.
Adverse reactions and side effects
Upon being subject to one-time injection of cisplatin for 50mg/m2, 25% to 30% of patients can get azotemia. Upon a larger dose and continuous medication, it can have serious and long-lasting kidney toxicity, manifested as tubular swelling, degenerative disease, elevated level of serum urea nitrogen, decreased creatinine clearance, hematuria, proteinuria, and even uremia.
It may have mild to moderate bone marrow toxicity whose degree depends on the amount of cisplatin. Anemia is common and may be accompanied with hemolysis. The patients can get severe nausea and vomiting which often appears at the beginning of treatment within 1h, lasting 8~12 h. The patients can administrate dexamethasone, ondansetron and diazepam to reduce the reaction.
It can cause malignant renal toxicity and is prone to occur at patients free from hydration and patients of diuretic therapy.
Combination with renal toxic antibiotics may increase the risk of enhancing acute renal failure.
It can commonly cause high-frequency hearing loss, and occasionally significant hearing loss. Tinnitus can occur at rare cases.
There may be significant symptoms of hyponatremia, hypomagnesemia, hypocalcemia, and hypokalemia which may occur in a few days after treatment.
After several times of administration can cause allergic reaction which can occur within minutes after administration, being manifested as facial edema, wheezing, tachycardia, etc. The patients should be quickly subject to anti-allergy measures such as antihistamine and adrenocorticotropic hormone.
There may be peripheral nerve toxicity. Hyperuricemia occurs rarely. There are occasional symptoms of orthostatic hypotension.
Originator
Blastolem,Lemery,Mexico
Indications
Cisplatin (Platinol) is an inorganic coordination complex
with a broad range of antitumor activity. It is especially
useful in the treatment of testicular and ovarian
cancer. It binds to DNA at nucleophilic sites, such as the
N7 and O6 of guanine, producing alterations in DNA
structure and inhibition of DNA synthesis. Adjacent
guanine residues on the same DNA strand are preferentially
cross-linked. This platinating activity is analogous
to the mode of action of alkylating agents. Cisplatin also
binds extensively to proteins. It does not appear to be
phase specific in the cell cycle.
Production Methods
Cisplatin is obtained by the method described by Kauffman
and Cowan, in which potassium(II) tetrachloroplatinate
is treated with buffered aqueous ammonia solution.
Pure cisplatin is obtained by recrystallization from dilute
hydrochloric acid.
Manufacturing Process
The synthesis proceeds dy reduction of potassium hexachlorplatinate with
hydrazine to give potassium tetrachloroplatinate. This is converted to
potassium tetraiodoplatinate by treatment with potassium iodide and then
reacted with 6 M ammonium hydroxide to give crystals of cisplatin
Therapeutic Function
Antitumor
Air & Water Reactions
Insoluble in water.
Reactivity Profile
Cisplatin is incompatible with oxidizing agents. Cisplatin is also incompatible with aluminum. Cisplatin may react with sodium bisulfite and other antioxidants.
Fire Hazard
Flash point data for Cisplatin are not available; however, Cisplatin is probably combustible.
Pharmaceutical Applications
CDDP, also referred to as cisplatinum or cisplatin, is a yellow powder and has found widespread use a
chemotherapeutic agent.
Biological Activity
Potent anticancer agent that blocks DNA synthesis. Induces apoptosis via p53-dependent and -independent mechanisms. Inhibits X-linked inhibitor of apoptosis protein (XIAP) expression and activates caspase-3. In certain glioma cell lines, sensitizes cells to TNF- α -induced apoptosis.
Biochem/physiol Actions
Potent platinum-based antineoplastic agent. Forms cytotoxic adducts with the DNA dinucleotide d(pGpG), inducing intrastrand cross-links.
Mechanism of action
Cisplatin shows biphasic plasma decay with a distribution
phase half-life of 25 to 49 minutes and an elimination
half-life of 2 to 4 days. More than 90% of the
drug is bound to plasma proteins, and binding may approach
100% during prolonged infusion. Cisplatin does
not cross the blood-brain barrier. Excretion is predominantly
renal and is incomplete.
Clinical Use
Cisplatin, combined with bleomycin and vinblastine
or etoposide, produces cures in most patients with
metastatic testicular cancer or germ cell cancer of the
ovary. Cisplatin also shows some activity against carcinomas
of the head and neck, bladder, cervix, prostate,
and lung.
Side effects
Renal toxicity is the major potential toxicity of
cisplatin. Severe nausea and vomiting that often accompany
cisplatin administration may necessitate hospitalization.
Cisplatin has mild bone marrow toxicity, yielding
both leukopenia and thrombocytopenia. Anemia is
common and may require transfusions of red blood
cells. Anaphylactic allergic reactions have been described.
Hearing loss in the high frequencies (4000 Hz)
may occur in 10 to 30% of patients. Other reported toxicities
include peripheral neuropathies with paresthesias,
leg weakness, and tremors. Excessive urinary excretion
of magnesium also may occur.
Safety Profile
Confirmed carcinogen
with experimental carcinogenic and
tumorigenic data. Poison by ingestion,
intramuscular, submtaneous, intravenous,
and intraperitoneal routes. Human systemic
effects: change in audttory acuity, change in
kidney tubules, changes in bone marrow,
corrosive to skin, depressed renal function
tests, hallucinations, nausea or vomiting.
Experimental teratogenic and reproductive
effects. Human mutation data reported.
When heated to decomposition it emits very
toxic fumes of Cland NOx. See also
PLATINUM COMPOUNDS.
Synthesis
Cisplatin, cis-diaminodichloroplatinum (30.2.5.1), is made by reducing potassium hexachloroplatinate by hydrazine to potassium tetrachloroplatinate, which reacts
with ammonia to give cisplatin (30.2.5.1) .
Potential Exposure
A potential danger to those involved in the manufacture, formulation and administration of this anticancer chemotherapy agent. Contact with water causes decomposition.
Veterinary Drugs and Treatments
In veterinary medicine, the systemic use of cisplatin is presently
limited to use in dogs. The drug has been, or may be, useful in a
variety of neoplastic diseases including squamous cell carcinomas,
transitional cell carcinomas, ovarian carcinomas, mediastinal carcinomas,
osteosarcomas, pleural adenocarcinomas, nasal carcinomas,
and thyroid adenocarcinomas.
Cisplatin may be useful for the palliative control of neoplastic
pulmonary effusions after intracavitary
administration.
In horses, cisplatin has been used for intralesional injection for
skin tumors.
Drug interactions
Potentially hazardous interactions with other drugs
Aldesleukin: avoid concomitant use.
Antibacterials: increased risk of nephrotoxicity
and possibly ototoxicity with aminoglycosides,
capreomycin, polymyxins or vancomycin.
Antipsychotics: avoid with clozapine, increased risk
of agranulocytosis.
Cytotoxics: increased risk of ototoxicity with
ifosfamide; increased pulmonary toxicity with
bleomycin and methotrexate.
Carcinogenicity
Cisplatin is reasonably anticipated to be a human carcinogen based on sufficient evidence of carcinogenicity from studies in experimental animals.
Metabolism
It is rapidly hydrated, resulting in a short plasma half-life of less than 30 minutes. It is eliminated predominantly via the kidney, but approximately 10% of a given dose undergoes biliary excretion. It is highly nephrotoxic and can cause significant damage to the renal tubules, especially in patients with preexisting kidney disease or one kidney or who are concurrently receiving other nephrotoxic drugs (e.g., cyclophosphamide or ifosfamide). Dosages should be reduced in any of the above situations. Clearance decreases with chronic therapy, and toxicities can manifest at a late date. To proactively protect patients against kidney damage, patients should be hydrated with chloride-containing solutions. Saline or mannitol diuretics can be administered to promote continuous excretion of the drug and its hydrated analogues. Sodium thiosulfate, which accumulates in the renal tubules, also has been used to neutralize active drug in the kidneys in an effort to avoid nephrotoxicity.
Shipping
UN2928 Toxic solids, corrosive, organic, n.o.s., Hazard Class: 6.1; Labels: 6.1-Poisonous materials, 8-Corrosive material, Technical Name Required. UN3290 Toxic solid, corrosive, inorganic, n.o.s., Hazard class: 6.1; Labels: 6.1-Poisonous materials, 8-Corrosive material. UN3288 Toxic solids, inorganic, n.o.s., Hazard Class: 6.1; Labels: 6.1-Poisonous materials, Technical Name Required. UN3249 Medicine, solid, toxic, n.o.s., Hazard Class: 6.1; Labels: 6.1-Poisonous materials
Purification Methods
Recrystallise it from dimethylformamide and check the purity by IR and UV-VIS spectroscopy. [Raudaschl et al. Inorg Chim Acta 78 143 1983.] HIGHLY TOXIC, SUSPECTED CARCINOGEN.
Incompatibilities
Aluminum reacts with cisplatin and decreases the drug’s effectiveness. Do not use any aluminum equipment to prepare or administer cisplatin.
Waste Disposal
Disposal of unused product must be undertaken by qualified personnel who are knowledgeable in all applicable regulations and follow all pertinent safety precautions including the use of appropriate protective equipment. For proper handling and disposal, always comply with federal, state, and local regulations
References
1) Van Waardenburg et al. (2004), Platinated DNA adducts enhance poisoning of DNA topoisomerase I by camptothecin; J. Biol. Chem,, 279 54502
2) Siddik et al. (2003), Cisplatin: mode of cytotoxic action and molecular basis of resistance; Oncogene, 22 7265
3) Seki et al. (2000), Cisplatin (CDDP) specifically induces apoptosis via sequential activation of caspase-8, -3 and -6 in osteosarcoma; Cancer Chemother. Pharmacol., 45 199
4) Nomura et al. (2004), Cisplatin inhibits the expression of X-linked inhibitor of apoptosis protein in human LNCaP cells; Urol. Oncol., 22 453
5) Raghavan et al. (2015), Dimethylsulfoxide inactivates the anticancer effect of cisplatin against myelogenous leukemia cell lines in in vitro assays.; Indian J. Phamracol., 47 322
Check Digit Verification of cas no
The CAS Registry Mumber 15663-27-1 includes 8 digits separated into 3 groups by hyphens. The first part of the number,starting from the left, has 5 digits, 1,5,6,6 and 3 respectively; the second part has 2 digits, 2 and 7 respectively.
Calculate Digit Verification of CAS Registry Number 15663-27:
(7*1)+(6*5)+(5*6)+(4*6)+(3*3)+(2*2)+(1*7)=111
111 % 10 = 1
So 15663-27-1 is a valid CAS Registry Number.
InChI:InChI=1/2ClH.2H3N.Pt/h2*1H;2*1H3;/q;;;;+2/p-2
15663-27-1Relevant articles and documents
Copper-free click-chemistry platform to functionalize cisplatin prodrugs
Pathak, Rakesh K.,McNitt, Christopher D.,Popik, Vladimir V.,Dhar, Shanta
, p. 6861 - 6865 (2014)
The ability to rationally design and construct a platform technology to develop new platinum(IV) [PtIV] prodrugs with functionalities for installation of targeting moieties, delivery systems, fluorescent reporters from a single precursor with the ability to release biologically active cisplatin by using well-defined chemistry is critical for discovering new platinum-based therapeutics. With limited numbers of possibilities considering the sensitivity of PtIV centers, we used a strain-promoted azide-alkyne cycloaddition approach to provide a platform, in which new functionalities can easily be installed on cisplatin prodrugs from a single PtIV precursor. The ability of this platform to be incorporated in nanodelivery vehicle and conjugation to fluorescent reporters were also investigated.
Glassy carbon electrodes deliver unpredictable reduction potentials for platinum(IV) antitumor prodrugs
McCormick, Meghan C.,Schultz, Franklin A.,Baik, Mu-Hyun
, p. 28 - 34 (2016)
Reductive activation of six-coordinate Pt(IV) complexes to afford square-planar Pt(II) complexes has exhibited surprisingly divergent and unpredictable cathodic peak potentials during cyclic voltammetry (CV) measurements under widely employed experimental conditions. A systematic, detailed investigation reveals that glassy carbon (GC) electrodes are responsible for this erratic behavior. More reproducible CVs are obtained with platinum metal electrodes, which display cathodic responses at much more positive potentials. The unreliable and negatively shifted peak potentials observed at GC are attributed to a non-uniform oxide layer that is formed on the electrode surface causing slow electron transfer. A simple procedure of repetitive scanning to reducing potentials is found to be effective for cleaning and activating the GC surface, such that it exhibits the more consistent and accurate peak potential responses seen with a Pt electrode.
Cellular trafficking, accumulation and DNA platination of a series of cisplatin-based dicarboxylato Pt(IV) prodrugs
Ravera, Mauro,Gabano, Elisabetta,Zanellato, Ilaria,Bonarrigo, Ilaria,Alessio, Manuela,Arnesano, Fabio,Galliani, Angela,Natile, Giovanni,Osella, Domenico
, p. 1 - 8 (2015)
A series of Pt(IV) anticancer prodrug candidates, having the equatorial arrangement of cisplatin and bearing two aliphatic carboxylato axial ligands, has been investigated to prove the relationship between lipophilicity, cellular accumulation, DNA platination and antiproliferative activity on the cisplatin-sensitive A2780 ovarian cancer cell line. Unlike cisplatin, no facilitated influx/efflux mechanism appears to operate in the case of the Pt(IV) complexes under investigation, thus indicating that they enter by passive diffusion. While Pt(IV) complexes having lipophilicity comparable to that of cisplatin (negative values of log Po/w) exhibit a cellular accumulation similar to that of cisplatin, the most lipophilic complexes of the series show much higher cellular accumulation (stemming from enhanced passive diffusion), accompanied by greater DNA platination and cell growth inhibition. Even if the Pt(IV) complexes are removed from the culture medium in the recovery process, the level of DNA platination remains very high and persistent in time, indicating efficient storing of the complexes and poor detoxification efficiency.
Kinetic characterization of the interactions of trans-dichloro-platinum(IV) anticancer prodrugs and a model compound with thiosulfate
Dong, Jingran,Huo, Shuying,Song, Changying,Shen, Shigang,Ren, Yanli,Shi, Tiesheng
, p. 127 - 133 (2014)
Sodium thiosulfate has been utilized as a rescuing agent for relief of the toxic effects of cisplatin and carboplatin. In this work, we characterized the kinetics of reactions of the trans-dichloro-platinum(IV) complexes cis-[Pt(NH3)2Cl4], ormaplatin [Pt(dach)Cl 4] and trans-[PtCl2(CN)4]2- (anticancer prodrugs and a model compound) with thiosulfate at biologically important pH. An overall second-order rate law was established for the reduction of trans-[PtCl2(CN)4]2- by thiosulfate, and varying the pH from 4.45 to 7.90 had virtually no influence on the reaction rate. In the reactions of thiosulfate with cis-[Pt(NH3) 2Cl4] and with [Pt(dach)Cl4], the kinetic traces displayed a fast reduction step followed by a slow substitution involving the intermediate Pt(II) complexes. The reduction step also followed second-order kinetics. Reductions of cis-[Pt(NH3)2Cl 4] and [Pt(dach)Cl4] by thiosulfate proceeded with similar rates, presumably due to their similar configurations, whereas the reduction of trans-[PtCl2(CN)4]2- was about 1,000 times faster. A common reduction mechanism is suggested, and the transition state for the rate-determining step has been delineated. The activation parameters are consistent with transfer of Cl+ from the platinum(IV) center to the attacking thiosulfate in the rate-determining step.
Synthesis of pyrophosphatotetraamminediplatinum(II) complex and its transformations in hydrochloric acid solutions
Starkov,Patrushev
, p. 312 - 312 (2007)
A new method for the synthesis of [Pt2(NH3) 4P2O7] is proposed. Its transformations in a hydrochloric acid medium are described. Nauka/Interperiodica 2007.
Bioorthogonal Catalytic Activation of Platinum and Ruthenium Anticancer Complexes by FAD and Flavoproteins
Alonso-de Castro, Silvia,Cortajarena, Aitziber L.,López-Gallego, Fernando,Salassa, Luca
, (2018)
Recent advances in bioorthogonal catalysis promise to deliver new chemical tools for performing chemoselective transformations in complex biological environments. Herein, we report how FAD (flavin adenine dinucleotide), FMN (flavin mononucleotide), and fo
Synthesis and Cytotoxic Study of a Platinum(IV) Anticancer Prodrug with Selectivity toward Luteinizing Hormone-Releasing Hormone (LHRH) Receptor-Positive Cancer Cells
Yao, Houzong,Xu, Zoufeng,Li, Cai,Tse, Man-Kit,Tong, Zixuan,Zhu, Guangyu
, p. 11076 - 11084 (2019)
Platinum drugs including cisplatin are widely used in clinics to treat various types of cancer. However, the lack of cancer-cell selectivity is one of the major problems that lead to side effects in normal tissues. Luteinizing hormone-releasing hormone (LHRH) receptors are overexpressed in many types of cancer cells but rarely presented in normal cells, making LHRH receptor a good candidate for cancer targeting. In this study, we report the synthesis and cytotoxic study of a novel platinum(IV) anticancer prodrug functionalized with LHRH peptide. This LHRH-platinum(IV) conjugate is highly soluble in water and quite stable in a PBS buffer. Cytotoxic study reveals that the prodrug selectively targets LHRH receptor-positive cancer cell lines with the cytotoxicities 5-8 times higher than those in LHRH receptor-negative cell lines. In addition, the introduction of LHRH peptide enhances the cellular accumulation in a manner of receptor-mediated endocytosis. Moreover, the LHRH-platinum(IV) prodrug is proved to kill cancer cells by binding to the genomic DNA, inducing apoptosis, and arresting the cell cycle at the G2/M phase. In summary, we report a novel LHRH-platinum(IV) anticancer prodrug having largely improved selectivity toward LHRH receptor-positive cancer cells, relative to cisplatin.
Carboplatin decomposition in aqueous solution with chloride ions monitored by X-ray absorption spectroscopy
Curis,Provost,Nicolis,Bouvet,Benazeth,Crauste-Manciet,Brion,Brossard
, p. 1003 - 1008 (2000)
Carboplatin aqueous solutions, with chloride ions added at different concentrations, were studied by X-ray absorption spectroscopy (XAS). The comparison of solid and solution spectra shows that carboplatin and cisplatin spectra are strongly different, and that the carboplatin ligands induce a specific structure of the spectrum, conserved in solution. Hence, it is possible to study by XAS the evolution of carboplatin in solution. This study shows that carboplatin is the major compound present in solution, even after 15 days, in neutral solutions with chloride concentration less than 9%, exposed to light or not. On the contrary, with high chloride concentrations (18%) or in acidic solutions (0.1 M HCl), the carboplatin is chlorolysed, the evolution of the solution composition can be followed by XAS and cisplatin formation is evidenced.
Microwave-assisted synthesis of the anticancer drug cisplatin, cis-[Pt(NH3)2Cl2]
Petruzzella, Emanuele,Chirosca, Cristian V.,Heidenga, Cameron S.,Hoeschele, James D.
, p. 3384 - 3392 (2015)
A microwave-assisted synthesis of cisplatin, cis-[Pt(NH3)2Cl2], has been developed and optimized on both a 0.2 and 0.05 millimolar scale. The optimized synthetic procedure was modeled after the Lebedinskii-Golovnya method and is suitable for incorporating the radionuclide, 195mPt, into cisplatin for biological studies. Highest yields (47%) and purity are obtained using a K2PtCl4:NH4OAc:KCl molar ratio of 1:4:2 at a temperature of 100 °C. The entire synthesis and purification procedure requires approximately 80 min. At a reaction temperature of 150 °C, the trans isomer is the exclusive product, suggesting that complexes of the general form, trans-[Pt(RNH2)2Cl2], can be synthesized directly from K2PtCl4 using [RNH3]OAc (R = alkyl or aryl moieties) via a microwave process. Two novel separation procedures have been developed which efficiently remove the major impurity (1:1 Magnus-type salt) from the crude reaction product, yielding a product of purity comparable to that obtained by the Dhara method and suitable for biological studies. These procedures are applicable to both the micro- and macro-scale of synthesis. The question of whether this microwave-assisted synthesis of cisplatin will be a preferred method for incorporating 195mPt into cisplatin is yet to be determined. This journal is
Aluminum Doped MCM-41 Nanoparticles as Platforms for the Dual Encapsulation of a CO-Releasing Molecule and Cisplatin
Carmona, Francisco J.,Jiménez-Amezcua, Ignacio,Rojas, Sara,Rom?o, Carlos C.,Navarro, Jorge A. R.,Maldonado, Carmen R.,Barea, Elisa
, p. 10474 - 10480 (2017)
Mesoporous silica Al-MCM-41 nanoparticles have been used, for the first time, as vehicles for the single and dual encapsulation of the cationic CO-releasing molecule (CORM) [Mn(1,4,7-triazacyclononane)(CO)3]+ (ALF472+) and the well-known antineoplastic drug, cis-[PtCl2(NH3)2] (cisplatin). Thus, two new hybrid materials, namely, ALF472@Al-MCM-41 and ALF472-cisplatin@Al-MCM-41, have been isolated and fully characterized. The results reveal that the presence of CORM molecules enhances cisplatin loading 3-fold, yielding a cargo of 0.45 mmol g-1 of ALF472+ and 0.12 mmol g-1 of the platinum complex for ALF472-cisplatin@Al-MCM-41. It is worth noting that ALF472@Al-MCM-41 shows a good dispersion in phosphate buffered saline solution, while the dual hybrid material slightly aggregates in this simulated physiological medium (hydrodynamic size: 112 ± 23 and 336 ± 50 nm, respectively). In addition, both hybrid materials (ALF472@Al-MCM-41 and ALF472-cisplatin@Al-MCM-41) behave as photoactive CO-releasing materials, delivering 0.25 and 0.11 equiv of CO, respectively, after 24 h and exhibiting a more controlled CO delivery than that of the free CORM. Finally, metal leaching studies have confirmed the good retention capacity of Al-MCM-41 toward the potentially toxic manganese fragments (86% of retention after 72 h) as well as the low release of cisplatin (ca. 7% after 72 h).
