Benjamin S Murray

Newcastle University, Newcastle-on-Tyne, England, United Kingdom

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Publications (11)63.33 Total impact

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    ABSTRACT: Polymer-Scaffolded Dynamic Combinatorial Libraries (PS-DCLs) have been prepared in aqueous solution by the reversible conjugation of two different acylhydrazide residues onto aldehyde-functionalized dimethylacrylamide-based polymer scaffolds. PS-DCLs have been shown by 1H NMR spectroscopic analysis to adapt their composition in response to addition of three macromolecular template species, namely poly(sodium-4-styrenesulfonate), bovine serum albumin and bovine trypsin. Compositional changes within PS-DCLs in response to template addition may be rationalized in terms of multivalent interactions between members of the PS-DCL and templates. A systematic evaluation of how properties of the polymer scaffold, including molecular weight and density of aldehyde functionalities, affect the behaviour of resultant PS-DCLs is detailed. Increasing the molecular weight of the polymer scaffold has been shown to induce a linear decrease in the amplification of the preferred residue upon template addition. A linear relationship between the molar weight percentage of the aldehyde functionalized monomer and the extent of amplification of the preferred residue upon template addition has also been demonstrated.
    Polym. Chem. 12/2012; 4(2):368-377.
  • [Show abstract] [Hide abstract]
    ABSTRACT: Polymer-Scaffolded Dynamic Combinatorial Libraries (PS-DCLs) have been prepared in aqueous solution by the reversible conjugation of two different acylhydrazide residues onto aldehyde-functionalized dimethylacrylamide-based polymer scaffolds. PS-DCLs have been shown by 1H NMR spectroscopic analysis to adapt their composition in response to addition of three macromolecular template species, namely poly(sodium-4-styrenesulfonate), bovine serum albumin and bovine trypsin. Compositional changes within PS-DCLs in response to template addition may be rationalized in terms of multivalent interactions between members of the PS-DCL and templates. A systematic evaluation of how properties of the polymer scaffold, including molecular weight and density of aldehyde functionalities, affect the behaviour of resultant PS-DCLs is detailed. Increasing the molecular weight of the polymer scaffold has been shown to induce a linear decrease in the amplification of the preferred residue upon template addition. A linear relationship between the molar weight percentage of the aldehyde functionalized monomer and the extent of amplification of the preferred residue upon template addition has also been demonstrated.
    Polymer Chemistry 09/2012; 4:368–377. · 5.23 Impact Factor
  • Benjamin S. Murray, David A. Fulton
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    ABSTRACT: Polymeric nanoparticles were prepared through the chain collapse of linear polymers driven by the formation of dynamic covalent bonds. Linear chains of poly(vinylbenzaldehyde) were intramolecularly cross-linked through the formation of dynamic covalent acylhydrazone bonds with a bis-hydrazide cross-linker. The cross-linking density was shown to be controlled by the amount of cross-linker used. The resulting single polymer chain nanoparticles were then adorned through reaction of their remaining aldehyde units with a series of monoacyl hydrazides or alkoxyamines. Alternatively, the linear polymer chains could be fully adorned by reaction of their aldehyde units with the monoacyl hydrazides and then intramolecularly cross-linked through exchange reactions with the bis-hydrazide cross-linker. Both approaches proved effective routes to prepare single-chain polymer nanoparticles possessing high functional density.
    Macromolecules 09/2011; 44(18):7242-7252. · 5.93 Impact Factor
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    ABSTRACT: Image and spectral intensity from bicarbonate-selective europium(III) probes localised in the mitochondria of cells is modulated reversibly by variation of external pCO(2), and is suppressed by addition of the carbonic anhydrase inhibitor, acetazolomide.
    Chemical Communications 07/2011; 47(26):7347-9. · 6.38 Impact Factor
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    ABSTRACT: A water soluble polymer-scaffolded dynamic combinatorial library whose members can interconvert through acylhydrazone exchange was prepared and shown to re-equilibrate in the presence of macromolecular templates.
    Chemical Communications 07/2011; 47(25):7209-11. · 6.38 Impact Factor
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    ABSTRACT: Thermoresponsive copolymer scaffolds containing reactive aldehyde functions were prepared and a selection of organic residues conjugated to these copolymer scaffolds through oxime/hydrazone formation. The conjugation of hydrophobic residues affords copolymers whose lower solution critical temperatures are in most cases higher than that of the parent copolymer scaffold.
    Chemical Communications 10/2010; 46(45):8651-3. · 6.38 Impact Factor
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    ABSTRACT: To understand better the structure and function of biological systems, cell biologists and biochemists would like to have methods that minimally perturb living systems. The development of emissive optical probes is essential for improving our observation of intracellular signaling and recognition processes. Following excitation of the probe, photons emitted from the probe may be observed by spectroscopy or microscopy and encode information about their environments in their energy, lifetime, and polarization. Such optical probes may be based on organic fluorophores, quantum dots, recombinant proteins, or emissive metal complexes. In this Account, we trace the emergence of lanthanide coordination complexes as emissive optical probes. These probes benefit from sharp emission bands and long lifetimes. We can design these complexes to report on the concentration of key biochemical variables by modulation of spectral form, lifetime, or circular polarization. These properties allow us to apply ratiometric methods of analysis in spectroscopy or microscopy to report on local pH, pM (M = Ca, Zn), or the concentration of certain anionic metabolites, such as citrate, lactate, bicarbonate, or urate. For optical microscopy studies in living cells, these probes must be cell-permeable and, ideally, should localize in a given cell organelle. We undertook systematic studies of more than 60 emissive complexes, examining the time dependence of cellular uptake and compartmentalization, cellular toxicity, protein affinity, and quenching sensitivity. These results and their relationship to probe structure have allowed us to identify certain structure-activity relationships. The nature and linkage mode of the integral sensitizing group-introduced to harvest incident light efficiently-is of primary importance in determining protein affinity and cellular uptake and trafficking. In many cases, uptake may occur via macropinocytosis. We have defined three main classes of behavior: complexes exhibit predominant localization profiles in protein-rich regions (nucleoli/ribosomes), in cellular mitochondria, or in endosomes/lysosomes. Therefore, these systems offer considerable promise as intracellular optical probes, amenable to single- or two-photon excitation, that may report on the local ionic composition of living cells subjected to differing environmental stresses.
    Accounts of Chemical Research 03/2009; 42(7):925-37. · 20.83 Impact Factor
  • Jackie A Mosely, Benjamin S Murray, David Parker
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    ABSTRACT: Collision-induced dissociation (CID) and electron-capture dissociation (ECD) of lanthanide metal(III)-ligand complexes and lanthanide metal(III)-ligand-phosphopeptide complexes have been investigated using a Fourier transform-ion cyclotron resonance mass spectrometer (FT-ICR MS). Ternary adducts were formed for [LnL(3+)+solvent anion(s)(n-)]((3-n)+) [Ln=europium, terbium and ytterbium, L=heptadentate ligand, solvent anion=acetate or trifluoromethane-sulphonate (triflate)]. Results show that ECD provides much more diagnostically useful information than CID. ECD was found to systematically cleave N-C bonds in the "arms" of the ligand, similar to the N-C(alpha) cleavage of peptides, generating two fragmentation sites per arm of the ligand. The most intense and informative fragment ions were obtained from the terbium complex and it is believed that this is a consequence of terbium's greater reduction potential: the greater the reduction potential, the greater the ligand fragmentation; the lower the reduction potential, the more likely the molecule is to relinquish the solvent anion. The choice of solvent is also shown to be important. In general, the complexes studied fragment easily to lose CH(3)CO(2)H; however, particularly for ECD, the complexes retain the triflate anion causing the ligand to fragment instead, thus providing much more useful information. The triflate anion can be displaced by a phosphopeptide to create a lanthanide metal-ligand-phosphopeptide adduct. ECD is able to sequence the phosphopeptide, locating the site of phosphorylation bound to [LnL](3+) and also confirm the identity of the ligand. Small differences in the fragmentation of the lanthanide metal-ligand-phosphopeptide adducts follow the trend Eu <Tb <Yb suggesting that charge density may now be a more significant factor than metal ion reduction potential. ECD analysis of the triflate salts of the terbium complexes is most informative in developing a method to optimise structural information that can be gained from this group of molecules by mass spectrometry.
    European Journal of Mass Spectrometry 01/2009; 15(2):145-55. · 1.26 Impact Factor
  • Benjamin S Murray, Elizabeth J New, Robert Pal, David Parker
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    ABSTRACT: Five structurally related europium(iii) complexes of heptadentate macrocyclic ligands bearing azaxanthone or azathiaxanthone chromophores have been evaluated comparatively as responsive probes of the intracellular environment. Protein binding (HSA) and oxy-anion binding constants have been measured by titrimetric analysis, examining ratiometric emission changes for three examples, and systems exhibiting selectivity for citrate or hydrogencarbonate identified. The cytotoxicity of each ligand and complex has been assessed and correlated with the observed chemical stability profile in competitive aqueous media. The europium complex of L(2) is non-toxic, exhibits a large change in its emission spectral profile to variation in HCO(3)(-) (or citrate) concentration allowing ratiometric analysis, and localises in cellular mitochondria. Such features augur well for its future application as a responsive probe in microscopy to monitor local changes in pHCO(3).
    Organic & Biomolecular Chemistry 07/2008; 6(12):2085-94. · 3.57 Impact Factor
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    ABSTRACT: Observation of two-photon excitation (760 nm) and emission of two responsive water soluble europium complexes is reported with cross-sections of up to 2 GM. Two-photon excitation spectra have also been measured, acquisition being achieved by the use of a cavity-dumped mode locked Ti-sapphire laser. Time-gated detection is used to differentiate the ligand fluorescence and metal centred emission in these europium complexes.
    Dalton Transactions 01/2008; · 3.81 Impact Factor
  • Paul Atkinson, Benjamin S Murray, David Parker
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    ABSTRACT: The binding of two cationic europium complexes to a differentially phosphorylated insulin receptor peptide has been studied by emission spectroscopy and (31)P NMR and (1)H NMR TOCSY methods. Analysis of the europium emission and NMR spectral data was consistent with the presence of species in slow exchange on the NMR and emission timescales, in agreement with selective binding of the lanthanide ion to the phospho-tyrosine site, allowing such complexes to be considered as prototypical chemoselective paramagnetic derivatising agents.
    Organic & Biomolecular Chemistry 09/2006; 4(16):3166-71. · 3.57 Impact Factor