Lynne Wallace

Multinuclear ruthenium(II) complexes as anticancer agents

A series of dinuclear ruthenium(II) complexes that contain labile chlorido ligands, [{Ru(tpy)Cl}2{μ-bbn}]2+ {designated Cl-Rubbn; tpy = 2,2′:6′,2′′-terpyridine, bbn = bis[4(4′-methyl-2,2′-bipyridyl)]-1,n-alkane (n = 7, 10, 12, 14 or 16)} and derivatives containing nitro substituents on the tpy ligand and/or secondary amines within the bbn linking chain have been synthesised and their potential as anticancer agents examined. Some of the Cl-Rubbn species showed good anticancer activity against MCF-7 and MDA-MB-231 breast cancer cell lines, with the Cl-Rubb12 complex being four-times more active than cisplatin. Inclusion of nitro substituents on the tpy ligands of Cl-Rubb12 resulted in significantly decreased anticancer activity. The incorporation of amine groups into the linking ligand did not increase the anticancer activity of the Cl-Rubbn complexes. The Cl-Rubbn complexes and those containing amine groups in the linking chain aquated at approximately the same rate, with 50% aquation within 120 minutes. By comparison, the complexes containing nitro substituents on the tpy ligand aquated extremely slowly, with 60% of the chlorido complex remaining 24 hours after they were dissolved in water. Cyclic voltammetry with the model mononuclear complex [Ru{(NO2)3tpy}(Me2bpy)Cl]+ {(NO2)3tpy = 4,4′,4′′-trinitro-2,2′:6′,2′′-terpyridine} showed that the nitro substituents exerted a strong effect on the ruthenium centre, with the anodic peak corresponding to the Ru(III/II) couple shifted positively by 300 mV compared to that from the non-nitrated parent complex [Ru(tpy)(Me2bpy)Cl]+. 1H NMR studies of the reaction of the Cl-Rubbn complexes with GMP indicated that the ruthenium complexes covalently bound the nucleotide slowly, with 33% bound in 24 hours. However, the results of this study suggest that the cytotoxicity of the dinuclear ruthenium complexes is a combination of covalent and reversible binding with DNA.

Dynamical processes in the lowest-excited triplet metal-to-ligand charge transfer states of ruthenium and osmium diimine complexes in crystals

This review presents a detailed description of the lowest-excited states in ruthenium(II) and osmium(II) diimine complexes, based on extensive studies of their optical spectra in crystalline environments. Deuteration, and Zeeman and Stark effects provide a wealth of incisive results. The transferred charge in the lowest-excited triplet metal-to-ligand charge transfer states is localized on a single ligand in ruthenium(II) diimine complexes and the excitation exchange interaction between equivalent metal-ligand subunits is 0 5 cm . Localization gives rise to subtle effects, such as small Stokes shifts, in spectra. The lowest-excited states of osmium(II) diimine complexes in crystals with low inhomogeneous broadening are well described as coherent intramolecular excitons with excitation exchange interactions in the range from 2 to 30 cm .

Site‐selective and Stark spectroscopy of the series [Os(2,2’‐bipyridine)3−x(2,2’‐bipyridine‐d8)x]2+ (x=0–3) in single‐crystal [Ru(2,2’‐bipyridine)3](PF6)2. Localization of an intramolecular triplet metal‐to‐ligand charge transfer exciton by partial deuteration

Selective luminescence and excitation spectroscopy and Stark experiments of the title systems are reported. Dramatic differences of the x=1 and x=2 spectra, in comparison with the x=0 and x=3 spectra are observed. The lowest‐excited state in the x=1 and x=2 spectra is a charge‐transfer excitation localized on the protonated ligand(s). A superposition of ‘‘deuterated’’ and ‘‘protonated’’ transitions is observed for the x=1 and x=2 systems in the excitation spectra. The deuteration shift (≊32 cm−1) is much larger than the excitation exchange interaction β between the metal–ligand subunits. ‖β‖ is ≊2 cm−1, as directly determined from the observed splittings (5–7 cm−1) of I, the lowest‐energy electronic origin. Stark shifts confirm the charge transfer character of the lowest‐excited states. The splittings and relative intensities of the origins and their Stark effect can be quantitatively described by an exciton formalism.

Iridium(iii) Complexes Containing 1,10-Phenanthroline and Derivatives: Synthetic, Stereochemical, and Structural Studies, and their Antimicrobial Activity

A convenient synthetic strategy is reported for the series of complexes [Ir(pp)₃]³⁺ (where pp=phen, Me₂phen and Me₄phen) through the intermediacy of the appropriate [Ir(pp)₂(CF₃SO₃)₂]⁺ species. In the case of [Ir(phen)₃]³⁺, the cationwas resolved into its enantiomeric forms, for which the absolute configurations were determined by X-ray diffraction. The availability for the first time of the CD spectra allowed comparison with computed CD spectra. Measurement of the antimicrobial activity of the [Ir(pp)₃]³⁺ species {and the [Ir(pp)₂X₂]⁺ (X=Cl⁻, CF₃SO₃⁻) precursors involved in their synthesis}, as well as cell uptake studies with the four bacterial strains S. aureus, methicillin-resistant S. aureus (MRSA), E. coli, and P. aeruginosa, indicated that they showed little activity compared with their Ru(II) analogues. The results suggest that it is unfavourable for an individual metal centre with a 3+ charge to pass across the bacterial cell membrane.

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.

New high nitrogen compounds azoxytriazolone (AZTO) and azotriazolone (azoTO) as insensitive energetic materials

The new, electrochemically-synthesised high nitrogen materials AZTO and azoTO have been characterised by a range of techniques and compared to existing insensitive high explosives (IHE). AZTO, produced via electrolysis of aqueous NTO solutions, shows similar sensitiveness to NTO in most tests, but has better thermal stability. AzoTO displays higher thermal and impact stability than AZTO but is more sensitive to electrostatic discharge. AZTO sensitiveness is not affected by the presence of azoTO (formed concomitantly during synthesis) at levels of <20%. Crude samples and recrystallised samples react similarly in the tests performed. The ease of synthesis, low sensitiveness and moderate energy output suggest AZTO may be an economical and environmentally-friendly addition to the existing range of IHE.

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.

Electrochemical reduction of nitrotriazoles in aqueous media as an approach to the synthesis of new green energetic materials

The synthesis of new azo and azoxy compoundsvia electrochemical reduction of nitrotriazoles has been investigated in aqueous media, using nitrotriazolone (NTO) and nitrotriazole (NTr) as representative substrates. Reduction of NTO produces mainly solid azoxytriazolone (AZTO), with azotriazolone (azoTO) and aminotriazolone (ATO) as minor products, while 3-hydroxylaminotriazole is the major product formed from NTr. AZTO and azoTO are of interest as new green high-nitrogen compounds for use as insensitive high explosives (IHE). The effect of varying reaction conditions such as pH and substrate concentration has been evaluated, and a mechanism is proposed accounting for the experimental observations. In particular, the ratio of azoxy to azo in the solid product is influenced by pH and temperature, and the minor product ATO is formed not via direct reduction of NTO but via a novel thermal disproportionation reaction of the hydrazotriazolone intermediate. Conditions of high substrate concentration and low cell temperature maximise the azoxy yield and minimise the formation of minor products. Results indicate that this green electrosynthetic approach may be generally useful for the synthesis of new azoxy and azo triazoles from suitable substrates.

Non-photochemical spectral hole-burning mediated by water molecules in interligand pockets of [Cr(terpy)2]3+

Low temperature fluorescence line-narrowing (FLN) and spectral hole-burning experiments (SHB) were performed in the 2E←4A2 spin–flip transition of [Cr(2,2′:6′,2″-terpyridine)2]3+ in frozen ethylene glycol/water (2 ∶ 1) and DMSO/water (2 ∶ 1) glasses. In the FLN experiments an average 2E splitting of 23 cm−1 is observed. It is concluded that the interaction with water molecules in pockets provided by the ligands is most likely to be responsible for the relatively efficient non-photochemical hole-burning. Fast spectral diffusion and spontaneous hole-filling prevent the observation of holes above 20 K. The FLN and SHB experiments were performed by using a diode laser.

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 TPTPs inadequacy as a TATP pseudoscent is a valuable example of the limitations of such training aids.