Nicholas C. Fletcher

Protein surface recognition using geometrically pure Ru( ii ) tris(bipyridine) derivatives

Fac and mer isomers of functionalised ruthenium(ii) tris(bipyridine) derivatives are shown to have different recognition properties towards cytochrome c.

Enantiomeric programming in tripodal transition metal scaffolds

A new route to the isolation of the enantiopure tris-chelate complex (Δ/Λ)-fac-[Ru(L1)3]2+ (where L1 is 2,2′-bipyridine-5-carboxylic acid) is demonstrated, where the transition metal centre retains the memory of the chirality present in a simple tripodal tether used to control the metal centred geometry.

Benzothiazole bipyridine complexes of ruthenium(II) with cytotoxic activity

A series of benzothiazole-substituted trisbipyridine ruthenium(II) analogues {[Ru(bpy)2(4,5′-bbtb)]2+, [Ru(bpy)2(5,5′-bbtb)]2+ and [Ru(bpy)2(5-mbtb)]2+ [bpy is 2,2′-bipyridine, bbtb is bis(benzothiazol-2-yl)-2,2′-bipyridine, 5-mbtb is 5-(benzothiazol-2-yl),5′-methyl-2,2′-bipyridine]} have been prepared and compared with the complex [Ru(bpy)2(4,4′-bbtb)]2+ reported previously. From the UV–vis spectral studies, substitution at the 5-position of the bpy causes the ligand-centred transitions to occur at considerably lower energy than for those with the functionality at the 4-position, while at the same time causing the emission to be effectively quenched. However, substitution at the 4-position causes the metal-to-ligand charge transfer to occur at lower energies. Fluorescent intercalator displacement studies indicate that the doubly substituted complexes displace ethidium bromide from a range of oligonucleotides, with the greater preference shown for bulge and hairpin sequences by the Λ enantiomer. Since the complexes only show small variation in the UV–vis spectra on the introduction of calf thymus DNA and a small increase in fluorescence they do not appear to be intercalators, but appear to associate within one of the grooves. All of the reported bisbenzothiazole complexes show reasonable cytotoxicity against a range of human cancer cell lines.

Protein destabilisation by ruthenium(II) tris-bipyridine based protein-surface mimetics

Highly functionalised ruthenium(II) tris-bipyridine receptor 1 which acts as a selective sensor for equine cytochrome c (cyt c) is shown to destabilise the native protein conformation by around 25 °C. Receptors 2 and 3 do not exert this effect confirming the behaviour is a specific effect of molecular recognition between 1 and cyt c, whilst the absence of a destabilising effect on 60% acetylated cyt c demonstrates the behaviour of 1 to be protein specific. Molecular recognition also modifies the conformational properties of the target protein at room temperature as evidenced by ion-mobility spectrometry (IMS) and accelerated trypsin proteolysis.

The Use of Electrospray Mass Spectrometry to Determine Speciation in a Dynamic Combinatorial Library for Anion Recognition

The composition of a dynamic mixture of similar 2,2′-bipyridine complexes of iron(II) bearing either an amide (5-benzylamido-2,2′-bipyridine and 5-(2-methoxyethane)amido-2,2′-bipyridine) or an ester (2,2′-bipyridine-5-carboxylic acid benzylester and 2,2′-bipyridine-5-carboxylic acid 2-methoxyethane ester) side chain have been evaluated by electrospray mass spectroscopy in acetonitrile. The time taken for the complexes to come to equilibrium appears to be dependent on the counteranion, with chloride causing a rapid redistribution of two preformed heteroleptic complexes (of the order of 1 hour), whereas the time it takes in the presence of tetrafluoroborate salts is in excess of 24 h. Similarly the final distribution of products is dependent on the anion present, with the presence of chloride, and to a lesser extent bromide, preferring three amide-functionalized ligands, and a slight preference for an appended benzyl over a methoxyethyl group. Furthermore, for the first time, this study shows that the distribution of a dynamic library of metal complexes monitored by ESI-MS can adapt following the introduction of a different anion, in this case tetrabutylammonium chloride to give the most favoured heteroleptic complex despite the increasing ionic strength of the solution.

Chromo- and fluorogenic Organometallic Sensors

Compounds that change their absorption and/or emission properties in the presence of a target ion or molecule have been studied for many years as the basis for optical sensing. Within this group of compounds, a variety of organometallic complexes have been proposed for the detection of a wide range of analytes such as cations (including H+), anions, gases (e.g. O2, SO2, organic vapours), small organic molecules, and large biomolecules (e.g. proteins, DNA). This chapter focuses on work reported within the last few years in the area of organometallic sensors. Some of the most extensively studied systems incorporate metal moieties with intense long-lived metal-to-ligand charge transfer (MLCT) excited states as the reporter or indicator unit, such as fac-tricarbonyl Re(I) complexes, cyclometallated Ir(III) species, and diimine Ru(II) or Os(II) derivatives. Other commonly used organometallic sensors are based on Pt-alkynyls and ferrocene fragments. To these reporters, an appropriate recognition or analyte-binding unit is usually attached so that a detectable modification on the colour and/or the emission of the complex occurs upon binding of the analyte. Examples of recognition sites include macrocycles for the binding of cations, H-bonding units selective to specific anions, and DNA intercalating fragments. A different approach is used for the detection of some gases or vapours, where the sensors response is associated with changes in the crystal packing of the complex on absorption of the gas, or to direct coordination of the analyte to the metal centre.

The stereoselective coordination chemistry of the helicating ligand N,N′-bis(-2,2′-dipyridyl-5-yl)carbonyl-(S/R,S/R)-1,2-diphenylethylenediamine

Abstract Enantiomerically pure N , N ′-bis(-2,2′-dipyridyl-5-yl)carbonyl-(S/R,S/R)-1,2-diphenylethylenediamine has been synthesised by linking two 2,2′-bipyridine units by (R,R)- and (S,S)-1,2-diphenylethylenediamine. The ligands possess a hindered rotation between the bipyridine chromophores, which are held together by intramolecular hydrogen bonds. ES mass spectroscopy confirmed that reaction with Fe(II), Co(III) and Cd(II) afforded dinuclear complexes. CD spectroscopy implied that enantiopure ligands conferred helicity to the metals centre giving a dominant triple helicate diastereoisomer (with the RR isomer giving a P helicate). 1 H NMR spectroscopy of the cadmium complex confirmed the presence of a single diastereoisomer.

Stereoselective coordination chemistry of the tetradentate chelating ligand (2R,3R)-bis(2,2'-dipyridyl-5-methoxyl)butane

The enantiomerically pure ligand L3RR (2R,3R)-bis(2,2′-dipyridyl-5-methoxyl)butane has been synthesised by linking two 2,2′-bipyridine units with (2R,3R)-butandiol. The reaction of L3RR with Zn(II) afforded a mononuclear species and the 1H NMR spectroscopy points to a C1 symmetry, expected for a distorted trigonal bipyramidal coordination environment. These observations were confirmed by MM2 calculations and electrospray mass spectrometry. The reaction of L3RR with iron(II) indicated the formation of a dinuclear species by mass spectrometry. Solution state CD spectroscopy indicates that both complexes adopt a Λ-configuration, implying a single stranded dinuclear iron(II) complex is present rather than the anticipated triple helical architecture.

New insights into dihydrogenphosphate recognition with dirhenium(I) tricarbonyl complexes bridged by a thiourea moiety

Three thiourea bridged 2,2′-bipyridine ligands bearing either a single thiourea group (L1), or two units separated by either a para (L2) or meta-substituted (L3) aromatic spacer, along with the corresponding bis(fac-tricarbonylrhenium(I)) complexes are reported. The three ligands all show the anticipated binding to acetate. However 1H NMR titrations reveal an unusual cooperative binding to, and selectivity for, two dihydrogenphosphate ions. The rhenium(I) complexes similarly demonstrate unusual sigmoidal titration curves, and in the case of {Re(CO)3Br}2(μ-L1) a surprisingly strong interaction to two anions. These were further exemplified in the emissive behaviour leading to the conclusion that there is an unusual interaction with dihydrogenphosphate, giving an initial increase in the emission, followed by a decrease and a blue shift in wavelength possibly as a result of partial deprotonation. It appears that dihydrogenphosphate binds cooperatively, with the addition of a second anion enhancing the interaction of the first, probably by proton transfer; this could explain the remarkable selectivity for phosphate seen with many reported anion receptors.

Ruthenium cryptates with an unusual selectivity for nitrate

The synthesis of two new tripodal complexes [Ru(L3)](PF(6))(2) and [Ru(L4)](PF(6))(2), encapsulating a ruthenium(II) cation, has been successfully achieved and the products fully characterized, including by X-ray structural determination. The smaller cavity, built around a tris(2-aminoethyl)amido scaffold demonstrated only moderate and predictable interactions with a range of anions and no significant spectroscopic change with nitrate, chloride and bromide, although dihydrogen phosphate did result in an almost stoichiometric precipitation. The expansion of the cavity to include the more rigid 1,3,5-benzenetricarbonylamide group creates a larger cavity, which shows a decrease in the emission on the introduction of chloride, bromide, hydrogen sulfate and nitrate salts, with the (1)H NMR titrations giving a surprisingly high binding affinity for nitrate over the smaller and simpler halides.