Titanocene dichloride is utilized in the carbonyl olefination processes to prepare low-valent titanium compounds.

Absorption, Distribution and Excretion
In the present study, the subcellular distribution of titanium in the liver of mice was determined 24 and 48 hr after application of a therapeutic (ED100; ED = effective dose) and a toxic (LD25; LD= lethal dose) dose (60 and 80 mg/kg, respectively) of the antitumor agent titanocene dichloride by electron spectroscopic imaging at the ultrastructural level. At 24 hr titanium was mainly accumulated in the cytoplasm of endothelial and Kupffer cells, lining the hepatic sinusoids. Titanium was detected in the nucleoli and the euchromatin of liver cells, packaged as granules together with phosphorus and oxygen. One day later titanium was still present in cytoplasmic inclusions within endothelial and Kupffer cells, whereas in hepatocyte nucleoli only a few deposits of titanium were observed at 48 hr. At this time titanium was mainly accumulated in the form of highly condensed granules in the euchromatin and the perinucleolar heterochromatin. It was found in the cytoplasm of liver cells, incorporated into cytoplasmic inclusion bodies which probably respresent lysosomes. Sometimes these inclusions were situated near bile canaliculi and occasionally extruded their content into the lumen of bile capillaries. This observation suggests a mainly biliary elimination of titanium containing metabolites. These results confirm electron spectroscopic imaging to be an appropriate method for determining the subcellular distribution of light and medium weight elements within biological tissues. Insights into the cellular mode of action of titanocene complexes or titanocene metabolites can be deduced from the findings of the present study.
The passage of titaniun containing metabolites across the placenta into the embryonal compartment was investigated by analyzing the titanium content in embryos/fetuses at various intervals between 1 hr and 24 hr after treatment of pregnant mice with single doses of the antitumor agent titanocene dichloride (60 mg/kg) on days 10, 12, 14 or 16 of gestation. After treatment on days 10, 12 or 14, the titanium concentrations were not elevated in comparison to untreated embryos. Only on day 16, beyond the end of organogenesis, small amounts of titanium were detectable in the fetal compartment 4-24 hr after substance application, exceeding the control values by ranging between 2 and 3. These results explain the absence of histologic lesions in developing embryonal organs and the lack of multiple teratogenic effects in new-borns after application of therapeutic doses of titanocene dichloride to pregnant mice during the embryonal organogenesis.
The pharmacokinetics and organ distribution of titanium were analyzed at various intervals up to 96 hr after a single ip injection of a therapeutic dose of the antitumor agent titanocene dichloride (60 mg/kg). Highest organ concentrations were found in the liver and the intestine where 80-90 mg titanium/kg dry weight were accumulated at 24 and 48 hr, corresponding to liver/blood and intestine/blood ratios of 8-9.
The serum concentrations of cortisol, aldosterone, progesterone and catecholamines were determined 30 min, 1, 2, 4, 8, 24 and 48 hr after application of single doses of titanocene dichloride (60 mg/kg) to non-pregnant and to pregnant mice (treatment on day 10 of gestation). Titanocene dichloride induced 5-6 fold increases in serum cortisol concentration of pregnant as well as of non-pregnant mice within 1-2 hr after substance application. The serum levels of aldosterone, progesterone and catecholamines were not influenced by treatment with titanocene dichloride. It is supposed that the augmentation of cortisol in the serum is due to a rapid release of cortisol from the suprarenal glands after application of titanocene dichloride thus mediating indirectly the induction of cleft palate in mice.

Non-Human Toxicity Values
LD50 Rat ip 25 mg/kg
LD50 Mouse ip 60 mg/kg
LD50 Mouse iv 180 mg/kg

Titanocene dichloride appears as red to red-orange crystals. (NTP, 1992)

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Mechanism of Action
Dichloro-bis(etanidazole 5-cyclopentadienyl)titanium(IV) and some related complexes were compared with cis-dichlorodiammineplatinum(II) in rats for acute anti-inflammatory activity against carrageenan paw edema, anti-arthritic activity against developing and established adjuvant induced polyarthritis, immunosuppressant activity in a local graft versus host assay, irritant effects at sites of administration (paw, skin, peritoneum) and nephro- and gastro-toxicities. These titanium complexes, like cisplatin and its hydrolysis products, in vivo exhibited both anti-inflammatory and anti-arthritic activity as well as immunosuppressant effects. Nephro- and gastro-toxicity were much less severe than in rats given platinum complexes. In vitro they selectively inhibited (3)H-thymidine incorporation by isolated thymocytes and prevented the germination of radish seeds. When given intraperitoneally, the anti-inflammatory activity may partly be due to a counter-irritant phenomenon since the titanium derivatives elicited an acute peritoneal effusion if they were injected towards the omentum. However, when injected subcutaneously or applied in dimethylformamide or dimethylsulfoxide to the skin, they manifested both anti-inflammatory and anti-arthritic activity without irritancy or much local skin damage. They might therefore have the potential of being useful drugs, especially if released slowly.

C10H10CL2TI

248.96

247.963

1271-19-8

76030824

Bright red acicular crystals from toluene
Reddish-orange crystalline solid

1.6

41.5ºC at 760 mmHg

287-289ºC

3.295

0

4

0

13

11.6

0

[CH-]1C=CC=C1.[CH-]1C=CC=C1.[Cl-].[Cl-].[Ti+4]

YMNCCEXICREQQV-UHFFFAOYSA-L

InChI=1S/2C5H5.2ClH.Ti/c2*1-2-4-5-3-1;;;/h2*1-5H;2*1H;/q2*-1;;;+4/p-2

cyclopenta-1,3-diene;titanium(4+);dichloride

2934.99.9001

Powder      -20°C    3 years

                     4°C     2 years

In solvent   -80°C    6 months

                  -20°C    1 month

Note: (1). This product requires protection from light (avoid light exposure) during transportation and storage.  (2). Please store this product in a sealed and protected environment (e.g. under nitrogen), avoid exposure to moisture.

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

May dissolve in DMSO (in most cases), if not, try other solvents such as H2O, Ethanol, or DMF with a minute amount of products to avoid loss of samples

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.)