to synthetic variations as evidenced by the few probe
molecules derived from them.19-21 In this study, the applica-
tion of the versatile Cu(I)-catalyzed Huisgen cycloaddition
reaction, also widely known as the “click” reaction,22,23 offers
easy synthetic access to highly sensitive fluorescent probes
for Zn2+ featuring coordinating 1,2,3-triazolyl moieties.
1,2,3-Triazolyl is a structural mimic of imidazolyl in
histidine that binds Zn2+ in proteins.24 The 1,2,3-triazolyls
resulting from the Cu(I)-catalyzed click reaction have been
used extensively as linking units in projects ranging from
bioconjugation25 to surface sciences.26 Recently, the coor-
dination potential of 1,2,3-triazolyl has begun to be
exploited.27-30
containing motif A. Cu(I) and oxidized Cu(II) species in the
reaction mixture can be easily separated from the chelating
products by treating with EDTA during workup and subse-
quent alumina column chromatography. The click reaction
between arylacetylene and 1-azidoacetaldehyde dimethylac-
etal furnishes 4-aryl-1,2,3-triazolyl acetaldehyde 2. Reductive
amination between 2 and di(2-picolyl)amine gives rise to
probes featuring motif B.
Compounds 3-6 and 7-8 (Figure 2) were expected to
In this study, two tetradentate Zn2+ coordination motifs
were designed which were expected to chelate with Zn2+ to
afford a five-membered (Figure 1A)31 and a six-membered
Figure 2. Synthesized ligands 3-8.
form five-membered and six-membered coordination rings
with Zn2+, respectively. The X-ray crystal structures of [Zn-
(L)(AN)](ClO4)2 (Figure 3, L: 3 or 4, AN: acetonitrile)
Figure 1. (a) t-BuOH, L-sodium ascorbate, Cu(OAc)2, rt, 16 h;
(b) i. 1,2-dichloroethane, 16 h, rt; ii. NaBH(OAc)3, 4 h, Sol: solvent.
ring (Figure 1B), where N3 and N2 participate in binding,
respectively. In addition to the conventional functions of
1,2,3-triazolyls as covalent linkers, in both designs, they serve
as both chelating ligands to Zn2+ and transmitters of a
coordination event to the fluorophores (Ar in Figure 1).
The preparations of both motifs are outlined in Figure 1.
Briefly, diazotization of arylamines affords arylazides which
undergo the click reaction with 1 to afford molecules
Figure 3. ORTEP diagrams (50% probability ellipsoids) of Zn2+
complexes of 3 and 4. Perchlorate counterions are omitted for
clarity.
confirmed the N3-anchored five-membered coordination
rings. The bond lengths of the triazolyl-N3 and pyridyl
nitrogens to Zn2+ are in the range of 2.02-2.04 Å, similar
to those observed in the TPA-based Zn2+ complexes.18,32
(18) Allen, C. S.; Chuang, C.-L.; Cornebise, M.; Canary, J. W. Inorg.
Chim. Acta 1995, 239, 29-37.
(19) Dai, Z.; Xu, X.; Canary, J. W. Chem. Commun. 2002, 1414-1415.
(20) Dai, Z.; Proni, G.; Mancheno, D.; Karimi, S.; Berova, N.; Canary,
J. W. J. Am. Chem. Soc. 2004, 126, 11760-11761.
(21) Royzen, M.; Durandin, A.; Young, V. G. J.; Geacintov, N. E.;
Canary, J. W. J. Am. Chem. Soc. 2006, 128, 3854-3855.
(22) Rostovtsev, V. V.; Green, L. G.; Fokin, V. V.; Sharpless, K. B.
Angew. Chem., Int. Ed. 2002, 41, 2596-2599.
(27) Mindt, T. L.; Struthers, H.; Brans, L.; Anguelov, T.; Schweinsberg,
C.; Maes, V.; Tourwe, D.; Schibli, R. J. Am. Chem. Soc. 2006, 128, 15096-
15097.
(28) Liu, D.; Gao, W.; Dai, Q.; Zhang, X. Org. Lett. 2005, 7, 4907-
4910.
(29) Detz, R. J.; Heras, S. A.; de Gelder, R.; van Leeuwen, P. W. N.
M.; Hiemstra, H.; Reek, J. N. H.; van Maarseveen, J. H. Org. Lett. 2006,
8, 3227-3230.
(30) Bronisz, R. Inorg. Chem. 2005, 44, 4463-4465.
(31) When this manuscript was being prepared, Bergbreiter’s group
reported that coordination motif A (Figure 1A) can be incorporated in a
polymer to afford recyclable Cu(I) catalysts for the click reaction and the
atom transfer radical polymerization. Bergbreiter, D. E.; Hamilton, P. N.;
Koshti, N. M. J. Am. Chem. Soc. 2007, 129, 10666-10667.
(23) Tornoe, C. W.; Christensen, C.; Meldal, M. J. Org. Chem. 2002,
67, 3057-3064.
(24) Lippard, S. J.; Berg, J. M. Principles of Bioinorganic Chemistry;
University Science Books: Mill Valley, California, 1994.
(25) van Kasteren, S. I.; Kramer, H. B.; Jensen, H. H.; Campbell, S. J.;
Kirkpatrick, J.; Oldham, N. J.; Anthony, D. C.; Davis, B. G. Nature 2007,
446, 1105-1109.
(26) Collman, J. P.; Devaraj, N. K.; Decreau, R. A.; Yang, Y.; Yan,
Y.-L.; Ebina, W.; Eberspacher, T. A.; Chidsey, C. E. D. Science 2007, 315,
1565-1568.
5000
Org. Lett., Vol. 9, No. 24, 2007