Nickel is an essential cofactor for a variety of enzymes that play
important roles in microorganisms (bacteria, archea, fungi,
algea)228 and plants, particularly in energy and nitrogen
metabolism.229 As compared to other biological metals, nickel
is used at low levels; its use is relatively widespread in
microorganisms but more limited in eukaryotes.230 Yet, there
are very few Ni2+ selective indicators for live-cell imaging
(Table 8 and Figure 16). The Chang group presented one of
the first and only fluorescent sensors for cellular Ni2+,
Nickelsensor-1 (NS1).222 NS1 is composed of a BODIPYderived
fluorophore conjugated to a mixed N/O/S receptor.
This probe displays a 25-fold increase in fluorescence upon
binding Ni2+, although it binds with relatively low affinity (Kd =
193 μM). NS1 staining of human lung carcinoma A549 cells
incubated in extracellular NiCl2 (1 mM) was able to display an
increase in the intracellular Ni2+, suggesting the sensor can
detect increases over basal Ni2+ levels in mammalian cells. NS1
remains a platform from which more Ni2+ sensors can be
modeled to achieve Ni2+ detection in live cells with higher
dynamic range and altered affinities, for application in
microorganisms.