ORGANIC
LETTERS
2010
Vol. 12, No. 20
4486-4489
Probing Nitrobenzhydrol Uncaging
Mechanisms Using FerriCast
Daniel P. Kennedy, Daniel C. Brown, and Shawn C. Burdette*
Department of Chemisty, UniVersity of Connecticut, 55 North EagleVille
Road U- 3060, Storrs, Connecticut 06269, United States
Received July 23, 2010
ABSTRACT
The FerriCast derivative FC-NDBF was synthesized from 3-methyl-2-nitrodibenzofuran (NDBF). The photochemistry of the target Fe3+ photocage
and several related congeners provides mechanistic insight into the uncaging quantum yields of nitrobenzhydrol-derived ligands.
For over 30 years, photolabile protecting groups have been
incorporated into photocages to study biological pro-
cesses.1 Photocages render analytes inert until investigators
initiate activity with light. While most photocages are for
organic molecules, metal ions including Ca2+ and Cu2+
can be caged with photoactive chelators.2,3 Tsien designed
Nitr-photocages for Ca2+ based on converting a nitroben-
zhydrol-based ligand into a benzophenone.4 Upon uncaging,
electrons on a coordinated aniline delocalize onto a conju-
gated carbonyl group, which decreases the affinity for the
metal ion. Cast chelators, a name evocative of casting off a
metal ion, exploit this strategy to cage Mg2+,5 Zn2+,6 Hg2+,
and Pb2+.7
FerriCast (FC-DMNB) incorporates 7-phenyl-1-oxa-4,10-
dithia-7-azacyclododecane (AT212C4, 2) into a nitroben-
zhydrol scaffold (Scheme 1).8 Rurack et al. explored the
coordination chemistry of AT212C4 in a fluorescent sensor
for Fe3+.9 FC-DMNB utilizes a 4,5-dimethoxy-2-nitrobenzyl
(DMNB) caging chromophore and exhibits modest photolysis
quantum yields (Φ ) 0.05, ε350 ) 5700 cm-1 M-1) like other
nitrobenzhydrol-based photocages. In contrast, a nitrodiben-
zofuran-based (NDBF) Ca2+ photocage possesses Φ ∼ 0.7
and a high molar absorptivity (ε ) 18 400 cm-1 M-1) but
uses chelator fragmentation as the uncaging strategy.10 We
hypothesized that replacing the DMNB group with a NDBF
chromophore also would improve the uncaging efficiency
of FerriCast and related nitrobenzhydrol photocages, but no
practical route to useful NDBF precursors had been reported.
(1) Lee, H. M.; Larson, D. R.; Lawrence, D. S. ACS Chem. Biol. 2009,
4, 409–427.
(2) Ellis-Davies, G. C. R.; Kaplan, J. H. J. Org. Chem. 1988, 53, 1966–
1969
.
(7) Mbatia, H. W.; Kennedy, D. P.; Camire, C. E.; Incarvito, C. D.;
Burdette, S. C. Eur. J. Inorg. Chem. 2010, accepted.
(8) Kennedy, D. P.; Incarvito, C. D.; Burdette, S. C. Inorg. Chem. 2010,
49, 916–923.
(3) Ciesienski, K. L.; Haas, K. L.; Dickens, M. G.; Tesema, Y. T.; Franz,
K. J. J. Am. Chem. Soc. 2008, 130, 12246–12247
.
(4) Adams, S. R.; Kao, J. P. Y.; Grynkiewicz, G.; Minta, A.; Tsien,
R. Y. J. Am. Chem. Soc. 1988, 110, 3212–3220.
(9) Bricks Julia, L.; Kovalchuk, A.; Trieflinger, C.; Nofz, M.; Buschel,
M.; Tolmachev Alexei, I.; Daub, J.; Rurack, K. J. Am. Chem. Soc. 2005,
127, 13522–13529.
(5) Bandara, H. M. D.; Kennedy, D. P.; Akin, E.; Incarvito, C. D.;
Burdette, S. C. Inorg. Chem. 2009, 48, 8445–8455.
(6) Gwizdala, C.; Kennedy, D. P.; Burdette, S. C. Chem. Commun. 2009,
6967–6969.
(10) Momotake, A.; Lindegger, N.; Niggli, E.; Barsotti, R. J.; Ellis-
Davies, G. C. R. Nat. Methods 2006, 3, 35–40.
10.1021/ol101726a 2010 American Chemical Society
Published on Web 09/24/2010