D-(+)-Trehalose Dihydrate

• CAS: 6138-23-4
• Catalog Number: ACM6138234-2
• Category: Main Products
• Molecular Weight: 378.33
• Molecular Formula: C12H26O13
• Synonyms: D-Trehalose Dihydrate
• IUPAC Name: (2R,3S,4S,5R,6R)-2-(hydroxymethyl)-6-[(2R,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyoxane-3,4,5-triol
• InChI Key: HDTRYLNUVZCQOY-LIZSDCNHSA-N
• Boiling Point: 675.4ºC at 760 mmHg
• Melting Point: 97-99ºC
• Flash Point: 362.3ºC
• Density: 1.76 g/cm³
• Appearance: white solid
• Exact Mass: 378.13700
• Hazard Statements: Xi:Irritant
• H-Bond Acceptor: 11
• H-Bond Donor: 8
• Safety Description: S26-S37/39
• WGK Germany: 2

Case Study

D-Trehalose Dihydrate as a Hygroscopic Stabilizer Matrix for Spray-Dried Inhalation Formulations

Mah, Pei T., et al. European Journal of Pharmaceutics and Biopharmaceutics 144 (2019): 139-153.

D-Trehalose dihydrate is used as a protein-stabilizing carrier in spray-dried dry powder formulations for pulmonary delivery, and its inherent hygroscopicity makes moisture protection by hydrophobic amino acids essential for preserving aerosolization performance.
Experimental Protocol: Feed solutions containing 15 mg/mL total solids with trehalose-to-amino-acid weight ratios of 100:0, 80:20, 60:40 and 40:60 are atomized through a 0.7 mm two-fluid nozzle at an inlet temperature of 140°C, outlet temperatures of 69-72°C and a feed rate of 3.0 mL/min; powders are stored at 25°C and 50% relative humidity for 28 days. Solid-state changes are followed by powder X-ray diffractometry and dynamic vapor sorption, and aerosolization is assessed with an impactor at 100 L/min.
Performance Evaluation: Pure spray-dried trehalose has a glass transition temperature of 122.44°C and an emitted fraction of 59.12%, which rises to 83-92% upon amino acid addition. Whereas 20% w/w amino acid cannot prevent moisture-induced recrystallization, 40-60% w/w inhibits trehalose dihydrate crystallization over 28 days, and the 60% w/w L-isoleucine formulation withstands 90% relative humidity without recrystallizing while retaining fine particle fractions above 69%. Surface analysis shows that the 40-60% w/w formulations are enriched in amino acid at the particle surface, with L-isoleucine samples retaining more amino acid there than their L-leucine counterparts, explaining their greater moisture resistance.

D-Trehalose Dihydrate as a Lyoprotectant for Freeze-Drying Phase Transformation Studies

Sundaramurthi, Prakash, et al. Pharmaceutical research 27.11 (2010): 2374-2383.

D-Trehalose dihydrate is the crystalline form adopted by the lyoprotectant trehalose when it crystallizes in frozen solutions, and its phase behavior throughout freeze-drying is monitored to evaluate whether such crystallization compromises protein stabilization.
Experimental Protocol: Aqueous trehalose solutions are cooled from room temperature to -40°C, warmed to -18°C and annealed for up to 94 h, with some samples seeded with trehalose dihydrate or succinic acid crystals, while X-ray diffraction patterns are collected continuously. Primary drying proceeds at -25°C under 150 mTorr, followed by secondary drying at -10, 0 and 10°C, and differential scanning calorimetry complements the diffractometric analysis.
Performance Evaluation: Only hexagonal ice appears upon cooling, but annealing induces trehalose dihydrate crystallization within 12 h in seeded samples, and the dihydrate-ice eutectic melts between -2 and -3°C. During drying, dehydration converts the crystalline dihydrate into a substantially amorphous anhydrate, so the final lyophile appears amorphous despite earlier phase separation. These observations demonstrate that trehalose can crystallize during lyophilization, and that continuous monitoring of the entire cycle, rather than analysis of the dried product alone, is required to detect lyoprotectant phase separation.

D-Trehalose Dihydrate as a Cryoprotectant for Protein Stabilization in Aqueous Matrices

Olsson, Christoffer, et al. The Journal of Physical Chemistry B 120.20 (2016): 4723-4731.

D-Trehalose dihydrate provides the disaccharide component of protein-trehalose-water systems, acting as a glass-forming cryoprotectant that stabilizes proteins during cryopreservation and desiccation.
Experimental Protocol: Myoglobin and trehalose stock solutions are prepared at 5 mM and 20 mM concentrations and mixed to obtain water-to-trehalose molar ratios of 7 to 172 with 0-70 wt% protein; samples are hermetically sealed after controlled drying and analyzed by differential scanning calorimetry from -150 to 100°C at 10°C/min, while dynamic viscosity is measured between 10 and 40°C.
Performance Evaluation: In non-crystalline systems the glass transition temperature rises with both trehalose and protein content, whereas the protein denaturation temperature declines as protein increases, showing that matrix dynamics and protein stability are not directly coupled. Dynamic viscosity at 20°C increases from 1.30 to 40.44 mPa·s with rising trehalose and protein contents. Binary trehalose-water mixtures avoid water crystallization up to a water content of 36 wt%, and ternary samples behave as weighted averages of the binary systems, supporting preferential hydration of the protein by one to two water layers rather than direct trehalose-protein binding. Trehalose addition markedly raises the denaturation temperature relative to pure water, confirming its stabilizing role in cryopreservation media.

Custom Q&A

What is the molecular formula of D-(+)-Trehalose Dihydrate?

The molecular formula of D-(+)-Trehalose Dihydrate is C12H26O13.

What is the molecular weight of D-(+)-Trehalose Dihydrate?

The molecular weight of D-(+)-Trehalose Dihydrate is 378.33 g/mol.

What are the synonyms for D-(+)-Trehalose Dihydrate?

The synonyms for D-(+)-Trehalose Dihydrate are Trehalose dihydrate, D-Trehalose dihydrate, and alpha,alpha-Trehalose dihydrate.

When was D-(+)-Trehalose Dihydrate created?

D-(+)-Trehalose Dihydrate was created on July 19, 2005.

When was D-(+)-Trehalose Dihydrate last modified?

D-(+)-Trehalose Dihydrate was last modified on October 21, 2023.

What is the IUPAC name of D-(+)-Trehalose Dihydrate?

The IUPAC name of D-(+)-Trehalose Dihydrate is (2R,3S,4S,5R,6R)-2-(hydroxymethyl)-6-[(2R,3R,4S,5S,6R)-3,4,5-trihydroxy-6-(hydroxymethyl)oxan-2-yl]oxyoxane-3,4,5-triol;dihydrate.

What is the InChI of D-(+)-Trehalose Dihydrate?

The InChI of D-(+)-Trehalose Dihydrate is InChI=1S/C12H22O11.2H2O/c13-1-3-5(15)7(17)9(19)11(21-3)23-12-10(20)8(18)6(16)4(2-14)22-12;;/h3-20H,1-2H2;2*1H2/t3-,4-,5-,6-,7+,8+,9-,10-,11-,12-;;/m1../s1.

What is the Canonical SMILES of D-(+)-Trehalose Dihydrate?

The Canonical SMILES of D-(+)-Trehalose Dihydrate is C(C1C(C(C(C(O1)OC2C(C(C(C(O2)CO)O)O)O)O)O)O)O.O.O.

What is the CAS number of D-(+)-Trehalose Dihydrate?

The CAS number of D-(+)-Trehalose Dihydrate is 6138-23-4.

How many hydrogen bond donor counts does D-(+)-Trehalose Dihydrate have?

D-(+)-Trehalose Dihydrate has a hydrogen bond donor count of 10.

Synthetic Use

Downstream Synthesis Route 1

• 108-24-7
• 6138-23-4

• 50257-21-1

Reference: [1]Carbohydrate Research,1980,vol. 87,p. 287 - 293

Downstream Synthesis Route 2

• 76-83-5
• 6138-23-4

• 76-84-6
• 50705-44-7

Reference: [1]Carbohydrate Research,1980,vol. 84,p. 171 - 174

Downstream Synthesis Route 3

• 6138-23-4

• 73707-77-4

Reference: [1]Carbohydrate Research,1980,vol. 79,p. 225 - 234

* For details of the synthesis route, please refer to the original source to ensure accuracy.