Iodine-based oxidizers have been the standard for DNA and RNA synthesis since the advent of automated synthesizers.They are fast and efficient oxidizers, typically requiring less than 30 seconds for complete oxidation of phosphite triesters to phosphate triesters. However, while iodine-based oxidizers work well for most applications, there are some circumstances where non-aqueous oxidizers may be advantageous, especially where the bases or linkages being produced are sensitive to the presence of water and/or iodine during synthesis.
The use of (1S)-(+)-(10-camphorsulfonyl)-oxaziridine (CSO) has been investigated as a non-aqueous oxidizer in DNA synthesis.For example, we found that a 0.5M solution of CSO in acetonitrile worked well as an oxidizer for the synthesis of oligos containing multiple incorporations of 7-deaza-dG, compared with iodine oxidation which caused substantial degradation. CSO has also worked well in the synthesis of a long poly-dI oligo, which could not be prepared using iodine oxidation due to the sensitivity of the base.
CSO has been used for synthesizing oligos that incorporate the phosphonoacetate modification. A solution of 0.1M CSO is recommended for the oxidation of PACE modifications as the phosphonite internucleotide linkage is more easily oxidized than the phosphite internucleotide linkage. When synthesizing DNA-phosphonoacetate chimeric oligos, a 0.5M CSO solution is recommended.