Building block libraries and structural considerations in the self-assembly of polyoxometalate and polyoxothiometalate systems

Inorganic metal-oxide clusters form a class of compounds that are unique in their topological and electronic versatility and are becoming increasingly more important in a variety of applications. Namely, Polyoxometalates (POMs) have shown an unmatched range of physical properties and the ability to form structures that can bridge several length scales. The formation of these molecular clusters is often ambiguous and is governed by self-assembly processes that limit our ability to rationally design such molecules. However, recent years have shown that by considering new building block principles the design and discovery of novel complex clusters is aiding our understanding of this process. Now with current progress in thiometalate chemistry, specifically polyoxothiometalates (POTM), the field of inorganic molecular clusters has further diversified allowing for the targeted development of molecules with specific functionality. This chapter discusses the main differences between POM and POTM systems and how this affects synthetic methodologies and reactivities. We will illustrate how careful structural considerations can lead to the generation of novel building blocks and further deepen our understanding of complex systems

Tyrosine kinase inhibitors reprogramming immunity in renal cell carcinoma: rethinking cancer immunotherapy

Review article[Abstract] The immune system regulates angiogenesis in cancer by way of both pro- and antiangiogenic activities. A bidirectional link between angiogenesis and the immune system has been clearly demonstrated. Most antiangiogenic molecules do not inhibit only VEGF signaling pathways but also other pathways which may affect immune system. Understanding of the role of these pathways in the regulation of immunosuppressive mechanisms by way of specific inhibitors is growing. Renal cell carcinoma (RCC) is an immunogenic tumor in which angiogenesis and immunosuppression work hand in hand, and its growth is associated with impaired antitumor immunity. Given the antitumor activity of selected TKIs in metastatic RCC (mRCC), it seems relevant to assess their effect on the immune system. The confirmation that TKIs improve cell cytokine response in mRCC provides a basis for the rational combination and sequential treatment of TKIs and immunotherapy

Epstein-Barr Virus LMP2A Reduces Hyperactivation Induced by LMP1 to Restore Normal B Cell Phenotype in Transgenic Mice

Epstein-Barr virus (EBV) latently infects most of the human population and is strongly associated with lymphoproliferative disorders. EBV encodes several latency proteins affecting B cell proliferation and survival, including latent membrane protein 2A (LMP2A) and the EBV oncoprotein LMP1. LMP1 and LMP2A signaling mimics CD40 and BCR signaling, respectively, and has been proposed to alter B cell functions including the ability of latently-infected B cells to access and transit the germinal center. In addition, several studies suggested a role for LMP2A modulation of LMP1 signaling in cell lines by alteration of TRAFs, signaling molecules used by LMP1. In this study, we investigated whether LMP1 and LMP2A co-expression in a transgenic mouse model alters B cell maturation and the response to antigen, and whether LMP2A modulates LMP1 function. Naïve LMP1/2A mice had similar lymphocyte populations and antibody production by flow cytometry and ELISA compared to controls. In the response to antigen, LMP2A expression in LMP1/2A animals rescued the impairment in germinal center generation promoted by LMP1. LMP1/2A animals produced high-affinity, class-switched antibody and plasma cells at levels similar to controls. In vitro, LMP1 upregulated activation markers and promoted B cell hyperproliferation, and co-expression of LMP2A restored a wild-type phenotype. By RT-PCR and immunoblot, LMP1 B cells demonstrated TRAF2 levels four-fold higher than non-transgenic controls, and co-expression of LMP2A restored TRAF2 levels to wild-type levels. No difference in TRAF3 levels was detected. While modulation of other TRAF family members remains to be assessed, normalization of the LMP1-induced B cell phenotype through LMP2A modulation of TRAF2 may be a pathway by which LMP2A controls B cell function. These findings identify an advance in the understanding of how Epstein-Barr virus can access the germinal center in vivo, a site critical for both the genesis of immunological memory and of virus-associated tumors

Nanocluster formation and stabilization fundamental studies: Ranking commonly employed anionic stabilizers via the development, then application, of five comparative criteria

To start, a brief introduction is provided on the importance of transition-metal nanoclusters, on the need to develop and then apply methods to rank the nanocluster formation and then stabilizing abilities of commonly employed anions, solvents, cations, and polymers, and on the somewhat confused literature of nanocluster stabilization. The fundamental importance of surface-adsorbed anions in transition-metal nanocluster stabilization is noted, the reason the present studies begin with a study of nanocluster-stabilizing anions. Next, five criteria, as well as the associated experimental methods, are developed to evaluate the efficacy of nanocluster stabilizing agents. The criteria are of fundamental significance in that they allow the separation of stabilizing agent effects on nanocluster formation from those on nanocluster stabilization. The results from applying the five criteria to four commonly employed anions lead to the first "anion series" of relative nanocluster-formation and stabilizing abilities, at least for the Ir(0) nanoclusters examined and by the following five criteria: [(P2W15Nb3O61)(2)O](16-) (a Bronsted-basic polyoxoanion) > C6H5O73- (citrate trianion) > [-CH2-CH(CO2)-](n)(n-) (polyacrylate) similar to Cl-. In addition to the needed methods and the first anion series, six other (8 total) conclusions are reached, important insights in an area previously lacking hard information about which anions are the better choices for nanocluster formation and stabilization. The results are also of significance in establishing polyoxoanions, notably highly charged and basic polyoxoanions such as [(P2W15Nb3O61)(2)O](16-), as the present "Gold Standards" among currently known nanocluster stabilizing anions, and according to the above five criteria. Such standards provide a reference point for future work aspiring to develop even better nanocluster stabilizing anions, solvents, cations, and polymers or their combinations

The hydrogenphosphate complex of (1,5-cyclooctadiene)iridium(I), {[Bu4N][(1,5-COD)Ir center dot HPO4]}(n): Synthesis, spectroscopic characterization, and ES-MS of a new, preferred precursor to HPO42- and Bu4N+ stabilized Ir(0)(n) nanoclusters

The synthesis and characterization of a previously unknown, rare organometallic-phosphate complex, {[Bu4N][(1,5-COD)Ir.HPO4]}(n) (1), is described. Characterization of 1 was accomplished by elemental analysis, electrospray mass spectrometry (ES-MS), and H-1 and C-13 NMR which established the symmetry of the product as at least C-2 or C-5. The ES-MS reveals an interesting, Ir(I) to Ir(III) oxidative process with intense peaks displaying the Ir-191/Ir-193 isotopic distribution patterns expected for the fragments [(1,5-COD)Ir-III(HPO4)(2)](-), [(C8H11)(2)(Ir-III)(2)(PO4)(HPO4)(H2O)](-), and [(C8H11)(2)(Ir-III)(2)(PO4)(HPO4)(H2O)(2)](-). These fragments, in turn, provide evidence for a structure with two HPO42- groups attached to a single Ir, for example ring structures (of at least such C-2 or C-5 symmetry) such as {[Bu4N][(1,5-COD)Ir.HPO4]}(2). Complex 1 is significant since it is known to be the preferred, compositionally precise precursor to the prototype example of a recently discovered class of novel, HPO42- and Bu4N+ stabilized nanoclusters, (Bu4N)(2n)(2n+)[Ir(0)(n).(HPO4)(n)](2n-). Such nanoclusters are being extended, via their analogous hydrogenphosphate-organometallic precursors (1,5-COD)M+ (or 2+)/HPO42- (M = Rh(I), Ru(II), Pt(II)) to their corresponding, catalytically active [M(0)(n).(HPO4)(n)](2n-) nanoclusters

CHARACTERIZATION OF LARGE, POLYANIONIC INORGANIC MOLECULES - FAST-ATOM-BOMBARDMENT MASS-SPECTROMETRY OF P2W15NB3O62(9)- AND OF THE SUPPORTED ORGANOMETALLIC CATALYST PRECURSOR (1,5-COD)IR-CENTER-DOT P2W15NB3O62(8)-

Positive and negative ion FAB-MS (fast atom bombardment mass spectrometry) has been used to help characterize large polyoxoanions with molecular weights of up to 6300 mass units, specifically [BU4N]9P2W15Nb3O62 and the important polyoxoanion-supported iridium organometallic complex [Bu(4)N]Na-5(3)[(1,5-COD)Ir.P2W15Nb3O62]. A detailed assignment of more than 50 envelopes has been performed, including the comparison of experimental vs calculated molecular ion distributions for key fragments. Two main pathways account for the most common fragmentations in both positive and negative ion FAB-MS, the loss of WO3 and the loss of O (and/or H2O, the latter generally following cation exchange between H+ from the matrix and Bu(4)N(+) or Na+). The excellent agreement between the experimental and calculated isotopic ion distributions provides reliable molecular formulas, even for fragments differing by only a few mass units. A higher degree of fragmentation is observed in the negative ion mode; this provides interesting structural and mechanistic results, notably the formation of a ''P2W10Nb2O424-'' fragment analogous to the ''P2W12'' polyoxoanion described in the literature. Overall, the most important finding is that most of the peaks in such complicated mass spectra can be readily assigned in terms of simple mechanisms and now-established polyoxoanion-fragmentation chemistry

Molecular insights for how preferred oxoanions bind to and stabilize transition-metal nanoclusters: a tridentate, C-3 symmetry, lattice size-matching binding model

The recent discovery of an anion efficacy series for the formation and stabilization of transition-metal Ir(0)(n) nanoclusters, specifically P2W15Nb3O629- similar to SiW9Nb3O407- > C6H5O73- > [-CH2CH(CO2-)-](n)(n-) similar to OAc- similar to P3O93- similar to Cl- similar to OH--that is, polyoxoanions > citrate(3-) > other commonly employed nanocluster stabilizing anions, raises the question of what are the underlying factors behind this preferred order of stabilizers? A brief discussion of three relevant nanocluster papers in the literature, plus a concise summary of the relevant interfacial electrochemistry and surface science literature of C-3 symmetry SO42- binding to Ir(111) (as well as to Rh(111), Pt(111), Au(111) and Cu(1111)), are presented first as key background for the lattice size-matching model which follows in which tridentate anions coordinate to transition-metal nanocluster surfaces. A table of nanocluster formation and stabilization data for tridentate oxoanion stabilizers is presented, results which allow two fundamental, previously unavailable, important insights (out of 10 total insights): (i) the premier anionic stabilizers of transition-metal(0) nanoclusters present a tridentate, facial array of oxygen atoms for coordination to the metal(0) surface; and (ii) the preferred tridentate oxoanion stabilizers of nanoclusters are those that have the best match between the ligand O-O and surface Ir-Ir distances, all other factors being equal-that is, there is a previously unappreciated, geometric, anion-to-surface-metal lattice-size-matching component to the best anionic stabilizers of transition-metal nanoclusters. These are the first molecular-level insights for how the to-date premier tridentate, anionic stabilizers of transition-metal nanoclusters achieve their higher level of stabilization-a non-trivial advance since there was a lack previously of molecular-level insights into how transition-metal nanoclusters are stabilized. Four experimentally testable predictions of the C-3 symmetry, lattice size-matching model for nanocluster M(111) surfaces are presented and briefly discussed. One key prediction is that HPO42- is a heretofore unappreciated simple, effective and readily available stabilizer of Ir(0) and other transition-metal nanoclusters where there is a lattice-size match between the O-O and the surface M-M distances. Recent experimental evidence is summarized revealing that this prediction is, in fact, trite-that is, the third key, new finding of this work is (iii) the first rational design of a new nanocluster stabilizer, HPO42-, one shown to be as good a stabilizer as the common nanocluster stabilizer citrate(3-). The C-3 symmetry, lattice size-matching model is significant in seven additional ways which are detailed in the text and summary which follows

Iridium(0) nanocluster, acid-assisted catalysis of neat acetone hydrogenation at room temperature: Exceptional activity, catalyst lifetime, and selectivity at complete conversion

Acetone hydrogenation catalysis is important in applications such as heat pumps and fuel cells or in fulfilling the sizable demand for the product of selective acetone hydrogenation, 2-propanol. Reported herein is the discovery of a superior acetone hydrogenation catalyst- superior in terms of activity at low temperature, selectivity at complete conversion, and total catalyst lifetime. The new catalyst system consists of lr(0)(n) nanoclusters plus HCI easily and reproducibly formed from commercially available [(1,5-COD)-lrCI](2) under H-2. The resultant, room temperature, high activity, and highly selective (2/n)lr(0)(n) plus 2HCI catalyst system hydrogenates acetone at 22 degrees C and 40 psig of H-2 pressure to 95% 2-propanol and the rest diisopropyl ether at 100% conversion with 16400 total catalytic turnovers and with an initial turnover frequency of 1.9 s(-1) at 22 degrees C. When molecular sieves are added, the catalyst system becomes even more selective and long-lived, providing the complete and selective conversion of acetone to 100% 2-propanol with 188000 total turnovers. Also reported are initial kinetic, D-labeling and other mechanistic studies, a summary section detailing the four main findings, the "green chemistry" aspects, and the current main drawback (a limited catalytic lifetime due to nanocluster precipitation) of the present invention. A review of the extensive literature of acetone hydrogenation is also tabulated as part of the Supporting Information

Transition-metal nanocluster stabilization fundamental studies: Hydrogen phosphate as a simple, effective, readily available, robust, and previously unappreciated stabilizer for well-formed, isolable, and redissolvable Ir(0) and other transition-metal nanoclusters

This work tests the hypothesis that tridentate oxoanions are especially effective stabilizers of transition-metal nanoclusters when the O-O distance of the anions matches closely the M-M (M = metal) distance atop the nanocluster surface. Specifically, we test the hypothesis that HPO42- with its 2.5 Angstrom O-O distance is a very simple, effective, but previously unrecognized anion for the stabilization of transition-metal(O) nanoclusters such as those of Ir(O), where the Ir-Ir surface distance is ca. 2.6-2.7 Angstrom. This hypothesis is tested by the five criteria we recently developed. These criteria emphasize the ability of a given nanocluster-stabilizing anion to allow the formation of highly kinetically controlled, near-monodisperse (less than or equal to+/-15%) size distributions of nanoclusters and then to allow isolable and fully redissolvable nanoclusters that exhibit, once redispersed into solution, good catalytic activity and long catalytic lifetimes. The previously unknown precursor complex {[Bu4N] [(1,5-COD)Ir.HPO4]}(n), 1, was prepared and shown to be a preferred precursor for the reproducible formation of hydrogen phosphate- and tetrabutylammonium-stabilized transition-metal lr(O) nanoclusters. The nanocluster formation reaction was shown to follow the slow continuous nucleation (A --> B, rate constant k(1)) followed by fast autocatalytic surface growth (A + B --> 2B, rate constant k(2)) mechanism uncovered previously; this finding was then exploited by showing that nanocluster size control could be achieved as expected by adding excess HPO42- to lower the k(2)/k(1) ratio, resulting in the formation of smaller nanoclusters. A relatively rare experimental demonstration of the balanced reaction for nanocluster formation is also provided. Proton Sponge [i.e., 1,8-bis(dimethylamino)naphthalene] is shown to be a preferred scavenger of the 1 equiv of H+ byproduct formed from the H-2 reduction of the (1,5-COD)Ir(l)+ moiety in the nanocluster precursor to Ir(O) plus H+; positive effects of Proton Sponge on the resultant nanocluster catalytic lifetime are also demonstrated. Transmission electron microscopy (TEM) of the postcatalysis nanoclusters shows that agglomeration is a catalysis-inhibiting deactivation reaction. Overall, the results show that HPO42- is an effective anion for the formation, and then stabilization, of lr(O) transition-metal nanoclusters in acetone and with Bu4N+ countercations. More specifically, HPO42- rates alongside citrate(3-) in the developing series of anion efficacy for nanocluster formation, stabilization and catalytic activity: polyoxoanions > HPO42- similar to citrate(3-) > other commonly employed nanocluster-stabilizing anions. Since a reasonable match between the tridentate O-O distance in HPO42- and the M-M distances is present for the metals Fe, Co, Ni, Ru, Rh Ir, Pd, Re, Os, and Pt [i.e., the lattice size-matching criterion is fulfilled; Ozkar, S.; Finke, R. G. Coord. Chem. Rev. 2003 (submitted for publication)], our results imply that HPO42- merits consideration for nanocluster synthesis and stabilization any time M(O) nanoclusters of the above list of metals are planned. The additional advantages of HPO42- are also presented and briefly discussed, namely, its thermal robustness, its high resistance to reduction or oxidation, its valuable <SU