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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.  Fφrster 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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