Two azobenzenesulfonamide
molecules with thermally stable cis configurations
resulting from fluorination of positions ortho to
the azo group are reported that can differentially
regulate the activity of carbonic anhydrase in the trans and cis configurations. These fluorinated probes
each use two distinct visible wavelengths (520 and 410 or 460 nm)
for isomerization with high photoconversion efficiency. Correspondingly,
the cis isomer of these systems is highly stable
and persistent (as evidenced by structural studies in solid and solution
state), permitting regulation of metalloenzyme activity without continuous
irradiation. Herein, we use these probes to demonstrate the visible
light mediated bidirectional control over the activity of zinc-dependent
carbonic anhydrase in solution as an isolated protein, in intact live
cells and in vivo in zebrafish during embryo development.
The chiral cyclometalated π-allyliridium ortho-C,O-benzoate complex (R)-Ir-VIb derived from [Ir(cod)Cl]2, allyl acetate, 4-cyano-3-nitrobenzoic acid, and (R)-MeO-BIPHEP catalyzes the coupling of N-(p-nitrophenylsulfonyl) protected vinyl aziridine 3a with primary alcohols 1a–1l to furnish branched products of C-C bond formation 4a–4l with good levels of anti-diastereo- and enantioselectivity. In the presence of 2-propanol, but under otherwise identical conditions, vinyl aziridine 3a and aldehydes 2a–2l engage in reductive coupling to furnish an equivalent set of adducts 4a–4l with roughly equivalent levels of anti-diastereo- and enantioselectivity. Using the enantiomeric iridium catalysts, vinyl aziridine 3a reacts with unprotected chiral 1,3-diols 1m–1o in a site-selective manner to deliver the diastereomeric products of C-allylation syn-4m, 4n, 4o and anti-4m, 4n, 4o, respectively, with good isolated yields and excellent levels of catalyst-directed diastereoselectivity. These adducts were directly converted to the diastereomeric 2,4,5-trisubstituted piperidines syn-5m, 5n, 5o and anti-5m, 5n, 5o.
We report the synthesis and application of a small molecule probe for carbonic anhydrase (CA) to track holo-CA in cell lysates and live-cell models of zinc dyshomeostasis. The probe displays a 12-fold increase in fluorescence upon binding to bovine CA and also responds to human CA isoforms.
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