Interaction of the Large Host Q[10] with Metal Polypyridyl Complexes: Binding Modes and Effects on Luminescence.

Aqueous solution state host-guest systems have been studied, comprising the large host cucurbit[10]uril with luminescent cationic tris(polypyridyl) (PP) metal complexes [Ru(PP)3]2+ and [Ir(PP)3]3+. All complexes bind strongly with the host, with the overall complex charge and size having a minor effect on affinity but influencing the association dynamics and contribution from higher-order (1:2) host-guest species. The 1:2 species contributes more significantly to the binding equilibrium in the case of [Ru(phen)3]2+. The effect of the host upon emission is highly variable and depends on the electronic structure of the guest. The metal-to-ligand charge transfer (MLCT) emission of [Ru(PP)3]2+ is strongly quenched, in contrast to the large enhancements seen previously for MLCT emission of iridium cyclometalated complexes, while the ligand-centered emission of [Ir(PP)3]3+ is little affected. The mechanisms of quenching and enhancement are discussed, together with the implications for the design of larger supramolecular assemblies based on these archetypal emitters.

Modelling the luminescence of iridium cyclometalated complexes encapsulated in cucurbituril.

Iridium(iii) cyclometalated complexes in aqueous solution often display relatively weak luminescence. It has been shown in previous work that this emission can be significantly enhanced (by up to two orders of magnitude) by encapsulation in cucurbit[10]uril (Q[10]). Luminescence lifetime measurements suggest a dynamic self-quenching mechanism is active, possibly due to displacement of an excited guest complex via collision with an unbound complex. We devise a model for the association of a group of iridium(iii) cyclometalated complexes with Q[10]. The model parameters are then fitted to steady-state emission titration curves. The excellent agreement of experimental data with the model provides valuable mechanistic information relating to the way this class of metal complexes interact and associate with the Q[10] host.

Encapsulation of Mitoxantrone within Cucurbit[8]uril Decreases Toxicity and Enhances Survival in a Mouse Model of Cancer.

Mitoxantrone was efficiently encapsulated within cucurbit[8]uril in a 2:1 complex where the two mitoxantrone molecules were symmetrically located through both portals of a cucurbit[8]uril cage. The novel complex facilitates increased mitoxantrone uptake in mouse breast cancer cells and decreases the toxicity of the drug in healthy mice. In an orthotopic mouse model of metastatic breast cancer the complex still maintains in vivo anticancer activity compared to the free drug, yet provides a statistically significant increase in the survival of these mice compared to conventional mitoxantrone treatment. This new low toxicity formulation offers the possibility to increase mitoxantrone dose and thus maximize efficacy while managing the dose limiting side effects.

Iridium Cyclometalated Complexes in Host-Guest Chemistry: A Strategy for Maximizing Quantum Yield in Aqueous Media.

The weaker emission typically seen for iridium(III) cyclometalated complexes in aqueous medium can be reversed via encapsulation in cucurbit[10]uril (Q[10]). The Q[10] cavity is shown to effectively maximize quantum yields for the complexes, compared to any other medium. This may provide significant advantages for a number of sensor applications. NMR studies show that the complexes are accommodated similarly within the host molecule, even with cationic substituents attached to the ppy ligands, indicating that the hydrophobic effect is the dominant driving force for binding. Cavity-encapsulated 1:1 host-guest species dominate the emission, but 1:2 species are also indicated, which also give some enhancement of intensity. Results demonstrate that the enhancement is due primarily to much lower rates of nonradiative decay but also suggest that the encapsulation can cause a change in character of the emitting state.

Rapid degradation of cyclic peroxides by titanium and antimony chlorides.

First responders face extraordinary risks when dealing with organic peroxides such as TATP due to the extreme sensitivity of this class of explosives, and to a lack of a robust chemical means of safe and rapid neutralisation. The Lewis acids TiCl4 and SbCl3 have been found to demonstrate a novel degradation mechanism, with TiCl4 degrading a model cyclic peroxide in minutes when used in a two-fold excess, or ∼3 hours at half equivalence. The products cannot re-form peroxide compounds as is the case with acid degradation, suggesting the two mechanisms are fundamentally different. The Lewis acids mediate a rearrangement reaction in the cyclic peroxide backbone leading to relatively innocuous products through deactivation of oxidising O. Sub-stoichiometric TiCl4 reactions highlight a secondary reaction pathway that also leads to some oxidative chlorination products, possibly mediated by an unconfirmed titanium-oxychloride species. SbCl3 was found to exhibit similar reactivity to TiCl4, although at a slower rate. A mechanism is proposed, consistent with the observations for both stoichiometric and sub-stoichiometric quantities of TiCl4.

Tri- and tetra-nuclear polypyridyl ruthenium(II) complexes as antimicrobial agents.

A series of inert tri- and tetra-nuclear polypyridylruthenium(II) complexes that are linked by the bis[4(4'-methyl-2,2'-bipyridyl)]-1,n-alkane ligand ("bb(n)" for n = 10, 12 and 16) have been synthesised and their potential as antimicrobial agents examined. Due to the modular nature of the synthesis of the oligonuclear complexes, it was possible to make both linear and non-linear tetranuclear ruthenium species. The minimum inhibitory concentrations (MIC) of the ruthenium(II) complexes were determined against four strains of bacteria--Gram positive Staphylococcus aureus (S. aureus) and methicillin-resistant S. aureus (MRSA), and Gram negative Escherichia coli (E. coli) and Pseudomonas aeruginosa (P. aeruginosa). In order to gain an understanding of the relative antimicrobial activities, the cellular uptake and water-octanol partition coefficients (log P) were determined for a selection of the ruthenium complexes. Although the trinuclear complexes were the most lipophilic based upon log P values and showed the greatest cellular uptake, the linear tetranuclear complexes were generally more active, with MIC values <1 µM against the Gram positive bacteria. Similarly, although the non-linear tetranuclear complexes were slightly more lipophilic and were taken up to a greater extent by the bacteria, they were consistently less active than their linear counterparts. Of particular note, the cellular accumulation of the oligonuclear ruthenium complexes was greater in the Gram negative strains compared to that in the Gram positive S. aureus and MRSA. The results demonstrate that the lower antimicrobial activity of polypyridylruthenium(II) complexes towards Gram negative bacteria, particularly P. aeruginosa, is not strongly correlated to the cellular accumulation but rather to a lower intrinsic ability to kill the Gram negative cells.

Cyclic pentanone peroxide: sensitiveness and suitability as a model for triacetone triperoxide.

Research to counter the threat of organic peroxides such as triacetone triperoxide (TATP) is at times hampered by their inherent extreme sensitiveness and volatility. This work describes an approach to lowering some risks associated with the handling of TATP in the laboratory through the use of an analog species, tripentanone triperoxide (TPTP). Sensitiveness has been tested via standard methods. GCMS analysis has shown that TPTP degrades via similar mechanisms to TATP under a range of conditions. Slight differences in product composition were traced to side reactions which may also affect impurities present in homemade TATP synthesis. A pilot field trial was conducted to evaluate TPTP as a substitute for TATP in explosive detection dog (EDD) scent training. The degradation studies have yielded insights into the complexities of the acidic degradation of cyclic peroxides with potential forensic application, and TPTP's inadequacy as a TATP pseudoscent is a valuable example of the limitations of such training aids.

Strong enhancement of luminescence from an iridium polypyridyl complex via encapsulation in cucurbituril.

An exceptional, temperature-dependent enhancement of luminescence is reported upon encapsulation of an iridium(III) polypyridyl complex in cucurbit[10]uril (Q[10]). This is the first demonstrated example of a luminescent transition metal complex occupying the Q[10] cavity with this type of differential response.

Chlorido-containing ruthenium(II) and iridium(III) complexes as antimicrobial agents.

A series of polypyridyl-ruthenium(II) and -iridium(III) complexes that contain labile chlorido ligands, [{M(tpy)Cl}(2){µ-bb(n)}](2/4+) {Cl-Mbb(n); where M = Ru or Ir; tpy = 2,2':6',2''-terpyridine; and bb(n) = bis[4(4'-methyl-2,2'-bipyridyl)]-1,n-alkane (n = 7, 12 or 16)} have been synthesised and their potential as antimicrobial agents examined. The minimum inhibitory concentrations (MIC) and minimum bactericidal concentrations (MBC) of the series of metal complexes against four strains of bacteria - Gram positive Staphylococcus aureus (S. aureus) and methicillin-resistant S. aureus (MRSA), and Gram negative Escherichia coli (E. coli) and Pseudomonas aeruginosa (P. aeruginosa) - have been determined. All the ruthenium complexes were highly active and bactericidal. In particular, the Cl-Rubb(12) complex showed excellent activity against all bacterial cell lines with MIC values of 1 µg mL(-1) against the Gram positive bacteria and 2 and 8 µg mL(-1) against E. coli and P. aeruginosa, respectively. The corresponding iridium(III) complexes also showed significant antimicrobial activity in terms of MIC values; however and surprisingly, the iridium complexes were bacteriostatic rather than bactericidal. The inert iridium(III) complex, [{Ir(phen)(2)}(2){µ-bb(12)}](6+) {where phen = 1,10-phenanthroline) exhibited no antimicrobial activity, suggesting that it could not cross the bacterial membrane. The mononuclear model complex, [Ir(tpy)(Me(2)bpy)Cl]Cl(2) (where Me(2)bpy = 4,4'-dimethyl-2,2'-bipyridine), was found to aquate very rapidly, with the pK(a) of the iridium-bound water in the corresponding aqua complex determined to be 6.0. This suggests the dinuclear complexes [Ir(tpy)Cl}(2){µ-bb(n)}](4+) aquate and deprotonate rapidly and enter the bacterial cells as 4+ charged hydroxo species.

Succession planning in an academic medical center nursing service.

Succession planning is of strategic importance in any industry. It ensures the smooth transition from leader to leader and the ability of the organization to maintain the forward momentum as well as meet its operational and financial goals. Health care and nursing are no exception. In the complex and challenging world of health care today, leadership is critical to an organization's success and leadership succession is a key strategy used to ensure continuity of leadership and development of talent from within the organization. At Rush University Medical Center, a 667-bed academic medical center providing tertiary care to adults and children, the need for a focus on succession planning for the nursing leadership team is apparent as key leaders come to the end of their careers and consider retirement. It has become apparent that to secure the legacy and continue the extraordinary history of nursing excellence, care must be taken to grow talent from within and take the opportunity to leverage the mentoring opportunities before the retirement of many key leaders. To ensure a smooth leadership transition, nursing leadership and human resources partner at Rush University Medical Center to implement a systematic approach to leadership succession planning.

Cucurbit[10]uril binding of dinuclear platinum(II) and ruthenium(II) complexes: association/dissociation rates from seconds to hours.

A simpler method for the purification of cucurbit[10]uril (Q[10]) from the Q[10].Q[5] inclusion complex is reported. 1,12-Diaminododecane was used to displace Q[5], as opposed to the synthetic melamine derivative currently used. The binding of trans-[{PtCl(NH(3))(2)}(2)(micro-NH(2)(CH(2))(8)NH(2))](2+) (CT008) and [{Ru(phen)(2)}(2)(micro-bb(5))](4+) {phen = 1,10-phenanthroline; bb(5) = 1,5-bis[4(4'-methyl-2,2'-bipyridyl)]pentane} (Rubb(5)) to Q[10] was studied by (1)H NMR and luminescence spectroscopy, cyclic voltammetry and molecular modelling. The (1)H NMR resonances of the methylene protons in the bridging ligands of CT008 and Rubb(5) exhibited large upfield chemical shift changes upon addition of Q[10]. These shifts are indicative of encapsulation of the bridging ligand within the Q[10] cavity, with the metal centres positioned outside the portals. (1)H NMR-based kinetics experiments with Rubb(5) show the presence of a portal-bound intermediate which progresses to a completely encapsulated inclusion complex only after many hours. The large metal centres of Rubb(5) provide a restriction to the movement of the complex in and out of the cavity and result in binding kinetics that are slow on both the (1)H NMR and biological timescales. This result was consistent with molecular modelling simulations. Cyclic voltammetry showed that the Ru(III/II) couple of free Rubb(5) appeared at +1.058 V (vs Ag/AgCl), with the first ligand reduction observed as a shoulder ( approximately -1.38 V) on the edge of the solvent (water) front. The Q[10]-bound complex exhibited an anodic shift of 48 mV compared to the free metal complex. Luminescence spectroscopy of the binding of Rubb(5) to Q[10] yielded an approximate binding constant of 1.9 x 10(9) M(-1). Although CT008 was encapsulated within Q[10], the inclusion complex was not soluble in several buffers at pH 7.0. These results indicate that Q[10] is not an effective delivery vehicle for dinuclear platinum(II) anti-cancer drugs; however, due to the strong binding affinity and slow exchange rates, Q[10] does show considerable promise as a delivery mechanism for controlled slow release of large dinuclear ruthenium(II) complexes.

Electrochemical method applicable to treatment of wastewater from nitrotriazolone production.

Laboratory studies show that electrochemical oxidation of acidic nitrotriazolone (NTO) solutions results in complete mineralization, with ammonium nitrate as the only solution product Other products (carbon dioxide, carbon monoxide, and nitrous oxide) are eliminated as gases from the working electrode. No additional chemical loading is required for the process, and electricity isthe only input The process maytherefore represent a cost-effective and environmentally friendly method of remediation for wastewater from NTO manufacture. Electrolyses were carried out at different applied voltages and at NTO concentrations of 0.01 and 0.05 mol/L, and the results indicate that a higher oxidation rate results in a greater charge passed per mole of NTO oxidized and increased production of nitrous oxide. Mechanisms are proposed on the basis of competing oxidative pathways that account for all products formed and the total charge passed during the reaction.

Electrochemical remediation produces a new high-nitrogen compound from NTO wastewaters.

A new high-nitrogen molecule, identified as azoxytriazolone (AZTO), has been generated in high yield by electroreduction of acidic aqueous solutions of nitrotriazolone (NTO). The near-quantitative conversion appears to be driven by the low solubility of the product. AZTO precipitates readily, leaving the solution virtually free of organic material, and the process may therefore present an efficient and productive remediation method for wastewater from NTO manufacture. The chemical formula and molecular structure of AZTO indicate that it may be effective as an insensitive explosive.