Titanocene dichloride does not have a defined biological target as it is a chemical catalyst and metallocene reagent rather than a pharmacologically active compound. Its function is chemical—it serves as a catalyst for various organic transformations including epoxidation, C-C bond formation, and polymerization reactions. In biological systems, titanocene dichloride has been investigated for anticancer activity, where it may interact with DNA and proteins through coordination to phosphate groups and amino acid residues. However, the compound is primarily used as a catalyst and research reagent. When incorporated into pharmaceutical compounds, the titanocene scaffold can interact with biological targets through metal coordination.

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

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In vitro, titanocene dichloride exhibits anticancer activity against various cancer cell lines. The compound has been shown to induce apoptosis and cell cycle arrest in cancer cells through mechanisms involving DNA damage and oxidative stress. It also demonstrates catalytic activity in organic synthesis, including epoxidation of alkenes, polymerization of olefins, and cross-coupling reactions. In cell-based assays, titanocene dichloride shows concentration-dependent cytotoxicity against cancer cell lines with IC₅₀ values typically in the micromolar range. However, the compound is not used as a therapeutic agent in clinical practice. Its role is primarily as a research reagent and catalyst in organic synthesis and polymer chemistry.

In vivo, titanocene dichloride has been investigated for anticancer activity in animal models. The compound has shown antitumor activity against various tumor types in preclinical studies, including xenograft models. However, its clinical development has been limited by poor aqueous solubility, rapid hydrolysis, and unfavorable pharmacokinetics. The compound is not approved for human use as an anticancer agent. Its primary application remains as a catalyst and research reagent in organic synthesis. Any in vivo effects would be associated with its anticancer activity, but the compound is not used as a therapeutic agent in clinical practice. Its role is strictly chemical—providing catalytic and metallocene properties for organic synthesis and materials science research.

In vitro enzyme/receptor binding assays for titanocene dichloride are not standard as the compound is primarily a chemical catalyst. However, its anticancer activity has been studied using DNA binding assays, where the compound is incubated with DNA and binding is monitored by UV-Vis spectroscopy or gel electrophoresis. For cytotoxicity assays, cancer cells are treated with varying concentrations of the compound (typically 1-100 µM) for 24-72 hours, and cell viability is assessed using MTT or CellTiter-Glo assays. For catalytic applications, the compound is used as a catalyst in epoxidation reactions, where alkenes are treated with the catalyst and an oxidant (e.g., TBHP) to form epoxides.

In vitro cell culture experiments with titanocene dichloride typically involve anticancer activity studies. Cancer cell lines (e.g., HeLa, MCF-7, A549) are cultured in appropriate media and treated with the compound at concentrations ranging from 1-100 µM for 24-72 hours. Cell viability is assessed using MTT or CellTiter-Glo assays. Apoptosis is measured using Annexin V/PI staining or caspase activity assays. DNA damage is assessed by comet assay or γ-H2AX staining. The compound is dissolved in DMSO and diluted in culture medium. Cell cycle analysis is performed by flow cytometry after propidium iodide staining.

In vivo animal studies with titanocene dichloride typically involve xenograft models for anticancer evaluation. Tumor-bearing mice are treated with the compound intraperitoneally or intravenously at doses ranging from 5-50 mg/kg. Tumor volume is measured twice weekly, and body weight is monitored for toxicity. At study termination, tumors are excised for histopathological and biomarker analysis. Pharmacokinetic studies involve blood sampling at various time points for analysis of titanium levels by ICP-MS. Toxicology studies include histopathological examination of major organs. However, the compound is not used in clinical trials and is primarily a research reagent.

Absorption, Distribution and Excretion
This study used ultrastructural level electron spectroscopy imaging to determine the subcellular distribution of titanium in mouse liver. Measurements were taken 24 and 48 hours after administration of the antitumor drug titanium dichloride at therapeutic doses (ED100; ED = effective dose) and toxic doses (LD25; LD = lethal dose) (60 and 80 mg/kg, respectively). At 24 hours, titanium primarily accumulated in the cytoplasm of hepatic sinusoidal endothelial cells and Kupffer cells. Titanium was also detected in the nucleoli and euchromatin of hepatocytes, presenting as granules along with phosphorus and oxygen. One day later, titanium remained in intracytoplasmic inclusions of endothelial cells and Kupffer cells, while at 48 hours, only a small amount of titanium deposition was observed in the hepatocyte nucleoli. At this point, titanium primarily accumulated as highly concentrated granules in euchromatin and perinuclear heterochromatin. Titanium was also found in the cytoplasm of hepatocytes, encapsulated in intracytoplasmic inclusion bodies, which may represent lysosomes. Sometimes, these inclusion bodies are located near bile canaliculi, occasionally squeezing their contents into the bile capillary lumen. This observation suggests that titanium-containing metabolites are primarily excreted via bile. These results confirm that energy dispersive spectroscopy (EDS) is an effective method for determining the subcellular distribution of light and medium molecular weight elements in biological tissues. The results of this study contribute to a deeper understanding of the cellular mechanisms of action of titanium complexes or titanium metabolites. This study investigated the transplacental entry of titanium-containing metabolites into the embryo by analyzing the titanium content in embryos/fetuses of pregnant mice 1 hour to 24 hours after a single injection of the antitumor drug titanium dichloride (60 mg/kg) on days 10, 12, 14, or 16 of gestation. The results showed that, compared with untreated embryos, the titanium concentration in the embryos/fetuses did not increase after treatment on days 10, 12, or 14. Only on day 16, after organogenesis, within 4–24 hours post-administration, were trace amounts of titanium detected in the fetus, at levels 2–3 times higher than in the control group. These results explain why, after administration of therapeutic doses of titanocene dichloride to pregnant mice during embryonic organogenesis, no histological damage was observed in developing embryonic organs, and no multiple teratogenic effects were observed in newborns. Following a single intraperitoneal injection of a therapeutic dose of the antitumor drug titanocene dichloride (60 mg/kg), the pharmacokinetics and organ distribution of titanium over a period of up to 96 hours were analyzed. The highest concentrations of titanium were found in the liver and intestines, with accumulations of 80–90 mg/kg dry weight in the liver and intestines at 24 and 48 hours, respectively, corresponding to liver/blood and intestine/blood ratios of 8–9.
Following a single injection of titanium dioxide (60 mg/kg) into non-pregnant and pregnant mice (administered on day 10 of gestation), serum concentrations of cortisol, aldosterone, progesterone, and catecholamines were measured at 30 minutes, 1 hour, 2 hours, 4 hours, 8 hours, 24 hours, and 48 hours. Titanium dioxide increased serum cortisol concentrations by 5-6 times in both pregnant and non-pregnant mice within 1-2 hours after administration. Titanium dioxide treatment had no effect on serum aldosterone, progesterone, or catecholamine levels. It is speculated that the increase in serum cortisol is due to the rapid release of cortisol from the adrenal glands after titanium dioxide administration, thereby indirectly contributing to cleft palate development in mice.

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Pharmacokinetic properties of titanocene dichloride have been studied for its anticancer activity. Following intravenous administration, the compound is rapidly hydrolyzed in aqueous media to form titanocene dihydroxide and other species. The compound has poor aqueous solubility and bioavailability. Titanium is distributed to various tissues, with highest concentrations in the liver, kidney, and spleen. The compound is eliminated primarily via renal excretion. The elimination half-life is relatively short (hours). However, the compound is not intended for therapeutic use and has not been formally developed as a drug. Its pharmacokinetic properties are of academic interest rather than clinical relevance.

Non-Human Toxicity Values
Rat intraperitoneal LD50: 25 mg/kg
Mouse intraperitoneal LD50: 60 mg/kg
Mouse intravenous LD50: 180 mg/kg

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Titanocene dichloride is a skin and eye irritant and may be harmful if swallowed, inhaled, or in contact with skin. The compound contains titanium, which is generally considered to have low toxicity, but the organometallic nature of the compound may present additional hazards. Standard laboratory safety precautions should be followed when handling this compound, including the use of gloves, safety glasses, and working in a fume hood. The compound should be stored in a cool, dry place under inert atmosphere. No acute toxicity data are available. The compound is not intended for drug, household, or other uses.

Titanium dichloride is a red to orange-red crystal. (NTP, 1992) Mechanism of Action: In mice, dichlorobis(ethidazole-5-cyclopentadienyl)titanium (IV) and some of its related complexes were compared with cisplatin (II) to evaluate their acute anti-inflammatory activity against carrageenan-induced paw edema in rats, their anti-arthritic activity against developing and established adjuvant-induced polyarthritis, their immunosuppressive activity in local graft-versus-host assays, their irritant effects at administration sites (paw, skin, peritoneum), and their nephrotoxicity and gastric toxicity. These titanium complexes, like cisplatin and its hydrolysates, exhibited anti-inflammatory, anti-arthritic, and immunosuppressive effects in vivo. Their nephrotoxicity and gastric toxicity were significantly less compared to rats given platinum complexes. In vitro experiments showed that these compounds selectively inhibited the incorporation of 3H-thymidine into isolated thymocytes and prevented radish seed germination. When administered intraperitoneally, their anti-inflammatory activity may be partly attributed to a counter-stimulatory effect, as injection of titanium derivatives near the greater omentum can cause acute peritonitis. However, when administered subcutaneously or applied topically to the skin with dimethylformamide or dimethyl sulfoxide solutions, they exhibit anti-inflammatory and anti-arthritis activities without irritation or significant local skin damage. Therefore, they may have the potential to become effective drugs, especially in the case of sustained release.

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Titanocene dichloride is a metallocene compound used as a catalyst in organic synthesis and polymerization reactions. It is also known as bis(cyclopentadienyl)titanium dichloride. The compound has been investigated for anticancer activity, but its clinical development has been limited by poor aqueous solubility and rapid hydrolysis. It is used as a catalyst for epoxidation, C-C bond formation, and polymerization reactions. The compound has not undergone clinical trials and is not approved as a pharmaceutical. Its mechanism of action is catalytic—facilitating organic transformations through titanium-mediated reactions.

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

552 °F (NTP, 1992) ; 289 °C +/- 2 deg

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.)