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42312-G3
Bridging Biology and Nanochemistry: Metalloclusters as Bioimaging Agents and Biomineralization Scaffolds

Thomas Gerald Gray, Case Western Reserve University

����� A principal research focus in this laboratory since inception has been the synthesis and photochemical characterization of metal-metal bonded clusters.� Of primary interest are the hexanuclear molybdenum(II) and tungsten(II) halide clusters and the chalcogenide clusters of rhenium(III).� Figure 1 depicts their structure.� An octahedron of metal atoms resides within a cube of face-bridging ligands: halides for Mo^II and W^II; sulfide or selenide for Re^III.� Apical capping ligands radiate outward from the metallocore.� These entities collectively constitute the largest series of isoelectronic metal-metal bonded clusters known.� Undoubtedly their leading feature is their luminescence.� Emission results from excitation with ultraviolet or blue light; luminescence quantum yields in solution range from ca. 1�25% at room temperature, and triplet-state lifetimes are on the order of microseconds.

����� The principle investigator works to apply the excited-state properties of these clusters in biological settings, for optical biological imaging and photodynamic therapy.� Present efforts seek (a) amelioration of the toxicity associated with their heavy-metal compositions and (b) optimization of their multiphoton absorption capabilities.

Multiphoton-absorbing Metalloclusters.� Toward Reagents for Two-Photon Photo-dynamic Therapy.

� Two-photon excitation, when combined with photodynamic therapy allows ultraprecise cancer treatment in sensitive anatomical regions, such as the brain.� The Gray research laboratory has devised an energy transfer scheme, where multiphoton-harvesting antennae funnel energy into the triplet states of metalloclusters.� Scheme 1 depicts the excited-state concept.� Multiphoton excitation of the pendant stilbene moieties leads promptly to a ligand-centered singlet state.� F�rster energy transfer to the cluster, combined with intersystem crossing, affords a long-lived (microseconds) cluster-centered triplet state.� This triplet excited state then sensitizes oxygen to form therapeutic ¹O₂.� For these initial investigations, tri(stilbene) phosphine 1 of Protasiewicz and co-workers[1] was chosen as a two-photon absorber, Figure 2.� Stilbenes and their derivatives are now established two-photon chromophores, and tri(stilbene) phosphines are available from commercial reagents in gram quantities.�

Scheme 2 depicts a general strategy for ligand attachment to cluster cores.� Refluxing an N,N-dimethylformamide solution of the halide-terminated clusters with the free ligand affords site differentiated species [Re₆Se₈(Pstil₃)_nI_6�n]^2�n (a).� Clusters bearing four or five tri(stilbene) phosphines are obtainable this way.

Clusters having a smaller loading of tri(stilbene) phosphine ligands are obtainable from species passivated beforehand with an inert phosphine.� A family of [Re₆Q₈(PEt₃)_nX_{6 � n}]^{2 � n} (Q = S, X = Br; Q = Se, X = I) clusters is available from previous work.[2]^,[3]� In these species, the remaining halides are replaceable, either by direct substitution with phosphine or by de-halogenation with Ag^I or Tl^I reagents, Scheme 2 (b).� Efforts to obtain mixed phosphine clusters are underway.� Two-photon absorption cross section measurements are pending in the laboratory of Professor D. G. Nocera, MIT.� Results of these investigations will be disclosed with due speed.

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