Chemistry Reference
In-Depth Information
12.2.7
Zinc Complexes in Cell imaging
There are a range of zinc species related to or based upon the ATSM (diacetyl-bis(N4-methylthiosemicarbazone) ligand that
are fluorescent and have been applied in cell imaging, mainly as models for the non-emissive copper analogues [42]. The
copper analogues are applied as PET imaging agents with the positron-emitting radioisotope
64
Cu. While these complexes
are effective cell imaging agents, they are beyond the scope of this chapter. Regardless of the semantics of definition of the
d
-block, the electronic nature of the fluorescence of zinc ATSM (and zinc and other porphyrin complexes) makes them more
akin to organic fluorophores than the phosphorescent species that are the focus of this section.
12.2.8
summary of
d
-block Lumophores in Cell imaging
The work described in this chapter demonstrates that
d
-block lumophores have now been developed as viable cell imaging
agents and molecular probes, with examples from a range of metals and complex types illustrating successful methods to
overcome issues of uptake, localisation, and toxicity. The
d
6
family have been most widely studied, and amongst these it
appears that while iridium and ruthenium complexes have the most attractive photophysics in terms of tunable and/or
responsive emission and lifetime profiles, in terms of controlling uptake and localisation, rhenium has, to date, been most
successful.
12.3
f
f-bLoCk iMAging Agents
12.3.1
Photophysical Properties of Ln
iii
Luminophores
Although the majority of the trivalent lanthanide (Ce to Lu) ions (Ln
III
) (electronic configuration of [Xe]4
f
n
where n = 0-14)
are luminescent, the most important ions in the context of optical imaging are currently Sm
III
, Eu
III
, Tb
III
, dy
III
, and Yb
III
.
The luminescence from emissive Ln
III
originates from inner shell 4
f
-4
f
transitions, which are observably sharp in appear-
ance and characteristic of the specific ion: Ln
III
ions can possess emission bands that usefully address the UV, visible, or
NIR regions. The associated Stokes' shifts can be large, but are a function of the particular pathway for populating the
f
f-centred excited state. Lifetimes can be even longer (from micro- to millisecond domain) than those described earlier for
the phosphorescent
d
-block lumophores due to the forbidden nature of the
f-f
relaxation. Because the 4
f
-4
f
transitions are
symmetry (parity) forbidden, they possess very low molar absorptivities for direct excitation, so the established strategy
for overcoming this is to incorporate a sensitising chromophore (commonly known as an antenna group), which absorbs
light and transfers energy to the 4
f
excited state (the origin of the apparent Stokes' shift) via a mechanism that often, but
not exclusively, involves the triplet excited state of the sensitiser (Scheme 12.4). The antenna group can be covalently
attached to the ligand architecture or introduced via other means (as a co-ligand, for example). Although there is a vast
range of sensitising chromophores that have been studied for various Ln
III
, for Eu
III
and Tb
III
the choice is perhaps more
limited. For these ions, the antenna group must absorb light very effectively, but it must also possess a triplet state that is
of sufficient energy (i.e., >2000 cm
-1
) above the accepting Ln
III
state to allow sensitisation and prevent back energy transfer
(which generally results in low emission intensity from the Ln
III
). Chromophore types that have proved to be effective
sensitisers of the accepting states of Eu
III
5
d
0
(~17200 cm
-1
) and Tb
III
5
d
4
(~20400 cm
-1
) are generally based upon (poly)
aromatic, often heterocyclic antennae, which ideally (for the applications described here) absorb between 350-410 nm,
with intrinsically small singlet-triplet energy gaps. From an energetic perspective, it is worth noting that consideration of
the NIR emitting lanthanides such as Yb
III
(accepting state of
2
F
5/2
at
ca.
10200 cm
-1
) broadens chromophoric options sig-
nificantly [43]. The quantum yields of emissive Ln
III
complexes vary dramatically due to the extremely sensitive nature of
the 4
f
4f-centred excited states to O-H, N-H, and C-H vibrational manifolds, which provide efficient, non-radiative deactiva-
tion pathways; the efficiency of energy transfer between the antenna and lanthanide ion also determines overall quantum
yields. A classical approach to maximising the emissivity of Ln
III
complexes is to therefore inhibit the approach of water
solvent to the inner coordination sphere; high denticity, metal ion encapsulating ligands with hydrophobic peripheries can
achieve this very effectively [44].
A unique and advantageous attribute of luminescent Ln
III
complexes is the dependence of the emission spectral form and
lifetime on the coordination environment. Eu
III
is particularly valuable in this regard with sharp emission bands
5
d
0
→
7
F
J
(
J
= 0, 2, 3, 4) that are subtly sensitive to the nature/type of the donor and the coordination geometry at Eu
III
[45]. When com-
pared to the
d
-block lumophores described earlier, such behaviour presents unique opportunities in the design of responsive
probes; thus, binding events at Ln
III
can be interrogated directly using luminescence methods and ratiometric analyses (i.e.,
independent of probe concentration) [46]. For example, the affinity of Ln
III
for various anions is dictated by electrostatics
and the steric demand of the metal centre, in turn governed by the polydentate ligand, especially the arm substituents of
