Robert B. P. Elmes

Luminescent Ruthenium(II) Polypyridyl Functionalized Gold Nanoparticles; Their DNA Binding Abilities and Application As Cellular Imaging Agents

The synthesis and photophysical and biological investigation of Ru(II)-polypyridyl stabilized water-soluble, luminescent gold nanoparticles (AuNPs) are described. These structures bind to DNA and undergo rapid cellular uptake, being localized within the cell cytoplasm and nucleus within 4 h.

Photophysical and biological investigation of novel luminescent Ru(II)-polypyridyl-1,8-naphthalimide Tröger's bases as cellular imaging agents

The synthesis and photophysical properties of 1 and 2, two Ru(II)-polypyridyl based-1,8-naphthalimide Trögers bases, are described; these were found to stabilize double stranded DNA, undergo rapid cellular uptake, displaying good luminescence without affecting cell viability even after 24 hours of incubation.

Thiosquaramides: pH switchable anion transporters†

The transport of anions across cellular membranes is an important biological function governed by specialised proteins. In recent years, many small molecules have emerged that mimick the anion transport behaviour of these proteins, but only a few of these synthetic molecules also display the gating/switching behaviour seen in biological systems. A small series of thiosquaramides was synthesised and their pH-dependent chloride binding and anion transport behaviour was investigated using 1H NMR titrations, single crystal X-ray diffraction and a variety of vesicle-based techniques. Spectrophotometric titrations and DFT calculations revealed that the thiosquaramides are significantly more acidic than their oxosquaramide analogues, with pKa values between 4.0 and 9.0. This led to the observation that at pH 7.2 the anion transport ability of the thiosquaramides is fully switched OFF due to deprotonation of the receptor, but is completely switched ON at lower pH.

Colorimetric and luminescent sensors for chloride: Hydrogen bonding vs deprotonation

The synthesis and photophysical properties of four squaramide based fluorescent anion sensors (1-4) are described. These luminescent compounds showed selectivity for Cl(-) over various other anions with concomitant changes in both their UV/visible and fluorescence properties upon Cl(-) addition, attributed to initial H-bonding followed by NH deprotonation in the presence of excess Cl(-), signaled by a color change. The nature of the electron withdrawing aryl substituents is directly related to the H-bonding ability/acidity of the squaramide protons and can be used to tune the deprotonation behavior.

Sulfate-Selective Recognition by Using Neutral Dipeptide Anion Receptors in Aqueous Solution

The synthesis of six small peptide anion receptors based on thiourea and squaramide recognition moieties is described. These new receptors bind to tetrahedral sulfate anions with remarkable affinity and selectivity in aqueous solution as shown by NMR spectroscopy. Molecular modelling suggests that selectivity is mediated by a hydrogen bond network incorporating the amide backbone protons in a manner similar to that found in the sulfate-binding protein.

Synthesis and photophysical evaluations of fluorescent quaternary bipyridyl-1,8-naphthalimide conjugates as nucleic acid targeting agents

A family of organic molecules containing the DNA intercalating chromophores, 4-nitro- and 4-amino 1,8-naphthalimide, conjugated to a diquat derivative by an ‘orthogonal’ phenyl spacer have been prepared and characterised. Their binding interactions with double-stranded DNA were studied by a variety of spectroscopic techniques. These charged organic compounds are found to exhibit excellent binding affinities to DNA with binding constants comparable to those exhibited by metal complexes.

pH switchable anion transport by an oxothiosquaramide.

An oxothiosquaramide was shown to bind to chloride through hydrogen bonding interactions in DMSO and found to exhibit pH switchable choride transport across phospholipid bilayers via an antiport transport mechanism.

A simple umbelliferone based fluorescent probe for the detection of nitroreductase

A simple nitrobenzyl-umbelliferone (NCOU1) was synthesised containing a nitroreductase (NTR) trigger moiety. The presence of NTR, resulted in the fragmentation of the parent molecule and release of the highly emissive fluorophore umbelliferone via an NTR-catalyzed reduction of the nitro group. In the presence of the NTR enzyme, NCOU1 gave rise to a 5-fold increase in fluorescence intensity at 455 nm and was selective for NTR over other reductive enzymes. These results indicate that NCOU1 can be used as a simple assay for the detection of NTR.

Amino acid-based squaramides for anion recognition

Eight receptors 1–8 comprising an l-lysine scaffold modified at N- and C-termini with aliphatic alkyl chains and N,N′-alkyl amides, respectively, and bearing squaramide moieties on the amino acid side chain were synthesised by a combination of solid- and solution-phase chemistries and shown to complex various anions in 0.5% H2O in dimethyl sulfoxide-d6 solution. All of the receptors were found to bind Cl− , AcO− and BzO− via hydrogen-bond or acid–base interactions with the squaramide protons; however, 1 was found to bind to via hydrogen bonds formed between the anion and both the squaramide and amide NH moieties. Moreover, modification of both the N- and C-termini of the amino acids with different alkyl substituents had a negligible effect on their anion-binding properties while simultaneously conferring lipophilicities in a range that is optimal for molecules to behave as ‘drug-like’ systems as defined by Lipinskis rule of five. The results of this study demonstrate the versatility of such amino acid receptors as building blocks in the field of anion recognition.

Synthesis of Side-Chain Modified Peptides Using Iterative Solid Phase ‘Click’ Methodology

A series of side-chain modified peptides have been prepared via an iterative sequence of peptide couplings and azide–alkyne cycloadditions (‘click’ reactions) using Fmoc-solid phase peptide synthesis. This efficient modular synthetic route allows the systematic and sequential incorporation of a variety of side-chain modifications onto short peptides. The versatility of this approach was demonstrated by the synthesis of a series of short peptides with appended anion recognition motifs and fluorescent indicators.