Catalyst Free Click Reagent

Highly Functionalized Alkyne
Our company newly launched a highly functionalized alkyne "4,8-diazacyclononyne(DACN)" developed by Prof. Katsuhiko Tomooka and Dr. Kazunobu Igawa of Institute for Materials Chemistry and Engineering (IMCE), Kyushu University.1) The DACN has high reactivity
toward Huisgen reaction with azide along with high bioorthogonality despite its high thermal
stability. Furthermore, DACN has high functional diversity with introduction of function units tothe endocyclic nitrogen atoms.

DACN・Catalyst Free・High Click Reactivity
・High Thermal Stability
・High Bioorthogonality
・High Functional Diversity

Product List
Product
N,N'-bis(p-toluenesulfonyl)-4,8-diazacyclononyne
NTs, NTs-DACN
CAS ：1797508-57-6
FW ：432.56

N-o-nitrobenzenesulfonyl-N'-p-toluenesulfonyl4,8-diazacyclononyne

Product No.

Package05628-68

100 mg05628-65

25 mg

28197-68

100 mg28197-65

25 mg

37104-68

100 mg37104-65

25 mg

NNs, NTs-DACN
CAS：1797508-58-7
FW ：463.53

N-succinoyl-N'-p-toluenesulfonyl-4,8-diazacyclononyne
NSu, NTs-DACN
CAS：−FW ：378.44※Ts = p-toluenesulfonyl、Ns = o-nitrobenzenesulfonyl、Su = succinoyl

Advantages of DACN
1. High Click Reactivity
DACN has higher click reactivity toward azides than that of cyclooctyne derivative (OCT).2)
2. High Thermal Stability
Reported strained cyclic alkynes (e.g. DIFO 3), DIBAC 4)) occasionally show thermal decomposition in experimental operations and during storage.5) In sharp contrast, DACN is thermally stable compared with reported
bent cycloalkynes. For example, no significant decomposition and/or oligomerization were observed by heating in 80 °C toluene for 2 weeks, at least.
Our company supplies DACN as crystaline form.
3. High Bioorthogonality
Side reactions with bio-thiols become problem in biological applications of strained cyclic alkynes.6) In sharp
contrast, DACN shows high reaction specificity toward Huisgen reaction. No addition product was obtainedin the presence of p-toluenethiol at room temperature, although reaction with equimolar amount of benzyl
azide provides click reaction product quantitatively.
4. High Functional Diversity
A variety of functional units such as biological ligand, fluorescent tag, biotin tag, PEG chain, etc. can be introduced to endocyclic nitrogen and/or a terminal of succinic acid moiety of DACNs.

Reaction ExampleNTs, NTs-DACN reacts with equimolar amount of benzylazide at room temperature to afford
Huisgen reaction product 1 in quantitatively.

※Reaction rate of NTs, NTs-DACN is ca. 2.3 times faster than that of cyclooctyne (OCT).

Order of reactivity for Huisgen reaction with benzyl azide.

*The figures in parentheses are reaction rate constants in M-1s-1.

References1) R. Ni, N. Mitsuda, T, Kashiwagi, K. Igawa, K. Tomooka, Angew. Chem. Int. Ed. 2015, 54, 1190.
2) N. J. Agard, J. A. Prescher, C. R. Bertozzi, J. Am. Chem. Soc. 2004, 126, 15046.
3) J. A. Codelli, J. M. Baskin, N. J. Agard, C. R. Bertozzi, J. Am. Chem. Soc. 2008, 130, 11486.
4) M. F. Debets, S. S. van Berkel, S. Schoffelen, F. P. J. T. Rutjes, J. C. M. van Hest, F. L. van Delft, Chem. Commun. 2010, 46, 97.
5) H. Stöckmann, A. A. Neves, S. Stairs, H. Ireland-Zecchini, K. M. Brindle, F. J. Leeper, Chem. Sci. 2011, 2, 932.
6) R. van Geel, G. J. M. Pruijn, F. L. van Delft, W. C. Boelens, Bioconjugate Chem. 2012, 23, 392.