Aminium Ion Peptide Coupling Reagents

Local Guidelines.

School of ChemistryUniversity of Leeds

HBTU, HATU, TBTU.

Background

The peptide coupling reagents HBTU, HATU and TBTU are commonly used for peptide synthesis:

Recently a case has been reported when the operator of a peptide synthesis instrument became severely sensitised to HBTU and HATU. Exposure to the smallest quantities of the material caused a nasty skin and respiratory reaction. It is clear from this case that these reagents are nasty sensitising agents and so must be treated with care and caution. The related reagent HCTU does not appear to cause such a response and is a much safer reagent to use.(

HCTU has also been reported to give superior yields in coupling reactions. (

  • Wherever possible HBTU, HATU and TBTU should be replaced with the reagent HCTU.

If HBTU, HATU or TBTU are to be used they must be used in line with the following protocol.

PROTOCOL and COSHH ASSESSMENT

THE FOLLOWING CONSTITUTES A COSHH ASSESSMENT FOR THE REAGENTS HBTU, HATU and TBTU. This assessment should be used in conjunction with the COSHH assessment for any reaction that you are to perform.

Material

HBTU May be harmful if inhaled, absorbed through the skin or swallowed. May cause respiratory tract eye and skin irritation. SENSITIZER!

TBTU May be harmful if inhaled, absorbed through the skin or swallowed. May cause respiratory tract eye and skin irritation. SENSITIZER!

HATU May be harmful if inhaled, absorbed through the skin or swallowed. May cause respiratory tract eye and skin irritation. SENSITIZER!

HEALTH MONITORING

Any researcher who is to use HBTU or HATU must first have baseline health checks at Occupational Health. These can be arranged through the chair of the safety committee.

CONTROL MEASURES

These materials must only be handled in a fume cupboard. To weigh out the material pre weigh a screwtop vial or flask with stopper and then transfer the material in a fume cupboard before returning to the balance. Where possible use alternative reagents (HCTU). Eye protection must be worn. Lab coat and gloves must be worn.

Use other appropriate control measures for other components of the reaction.

First Aid

In case of contact with the skin wash the affected area immediately with luke warm water.

In case of contact with eye irrigate thoroughly with water or (preferably) sterile eye wash solution for at least 15 minutes.

If inhaled remove casualty to fresh air.

Fire Extinguishing

Carbon Dioxide or Dry powder as demanded by other reaction components.

Spillage

If spilled in a fume cupboard clean up the solid, dissolve in a suitable solvent and dispose of in solvent waste. If significant quantities of the compound are spilled outside the fume cupboard evacuate the immediate area and seek help from qualified safety personnel trained in the use of breathing apparatus.

Disposal After Experiment

Solutions containing HBTU, HATU and TBTU can be safely disposed of in solvent waste drums provided other materials are not present which require special treatment.

Assessment performed by Dr. S. L. Warriner 2/2/2004 with advice from University safety services and occupational health service.