Biomedical subjects

Linda Swanson

Publications and source records attributed to Linda Swanson.

4 recordsLinked to original sources

PubMed2006

Dinuclear monointercalating RuII complexes that display high affinity binding to duplex and quadruplex DNA.

The DNA duplex binding properties of previously reported dinuclear Ru(II) complexes based on the ditopic ligands tetrapyrido[3,2-a:2',3'-c:3'',2''-h:2'',3''-j]phenazine (tppz) and tetraazatetrapyrido[3,2-a:2'3'-c:3'',2''-l:2''',3'''-n]pentacene (tatpp) are reported. Photophysical and biophysical studies indicate that, even at high ionic strengths, these complexes bind to duplex DNA, through intercalation, with affinities that are higher than any other monointercalating complex and are only equalled by DNA-threaded bisintercalating complexes. Additional studies at high ionic strengths using the 22-mer d(AG(3)[T(2)AG(3)](3)) [G3] human telomeric sequence reveal that the dinuclear tppz-based systems also bind with high affinity to quadruplex DNA. Furthermore, for these complexes, quadruplex binding is accompanied by a distinctive blue-shifted "light-switch" effect, characterized by higher emission enhancements than those observed in the analogous duplex effect. Calorimetry studies reveal that the thermodynamics of duplex and quadruplex binding is distinctly different, with the former being entirely entropically driven and the latter being both enthalpically and entropically favored.

DNA↗

PubMed2006

Highly branched poly(N-isopropylacrylamide) for use in protein purification.

Poly(N-isopropylacrylamide)s with imidazole endgroups were used to separate a histidine-tagged protein fragment directly from a crude cell lysate. The polymers display a lower critical solution temperature that can be tuned to occur at a range of subambient temperatures. UV-visible spectra indicated differences in the binding in aqueous media of Cu(II) and Ni(II) to the imidazole endgroups. These changes in the UV-visible spectra were reflected in the solution/aggregation behavior of the polymers as studied by dynamic light scattering. The addition of Cu(II) disaggregated the polymers, and the polymer coil swelled. On the other hand, when Ni(II) was added the polymers remained aggregated in aqueous media. The polymers were used to purify residues 230-534 of the histidine-tagged breast cancer susceptibility protein his6-BRCA1. Cu(II) was found to be better suited to the formation of useful polymer-metal ion-protein complexes that display cloud points, since Ni(II)/polymer mixtures generated very little purified protein. The polymers were synthesized using a previously reported variation of the reversible addition-fragmentation chain termination (RAFT) methodology, using the chain transfer agent 3H-imidazole-4-carbodithioic acid 4-vinyl benzyl ester with N-isopropylacrylamide (NIPAM).

Acrylic Resins↗

PubMed2004

DNA binding of an organic dppz-based intercalator.

An improved synthesis of a water-soluble derivative of dipyrido[3,2-a:2',3'-c]phenazine (dppz) is reported. The structures of both dppz and the cation ethylene-bipyridyldiylium-phenazine dinitrate [[1][(PF(6))(2)]] have been obtained via X-ray crystallography. Metal complex derivatives of dppz are very well studied. However, using the water soluble [1][(NO(3))(2)], the nature of the interaction of a simple dppz unit with duplex DNA has been investigated for the first time. In both organic solvents and water, 1 displays unstructured luminescence, assigned to an intramolecular charge transfer. The emission is quenched on binding to natural and synthetic duplex DNA, including poly(dA).poly(dT). A variety of techniques reveal that the cation binds to DNA with an affinity comparable to those of many metal dppz complexes, via an intercalative binding mode.

Binding Sites↗

PubMed2004

Complexes of substituted derivatives of 2-(2-pyridyl)benzimidazole with Re(I), Ru(II) and Pt(II): structures, redox and luminescence properties.

N,N'-Chelating ligands based on the 2-(2-pyridyl)benzimidazole (PB) core have been prepared with a range of substituents (phenyl, pentafluorophenyl, naphthyl, anthracenyl, pyrenyl) connected to the periphery via alkylation of the benzimidazolyl unit at one of the N atoms. These PB ligands have been used to prepare a series of complexes of the type [Re(PB)(CO)(3)Cl], [Pt(PB)(CCR)(2)](where -CCR is an acetylide ligand) and [Ru(bpy)(2)(PB)][PF(6)](2)(bpy = 2,2'-bipyridine). Six of the complexes have been structurally characterised. Electrochemical and luminescence studies show that all three series of complexes behave in a similar manner to the analogous complexes with 2,2'-bipyridine in place of PB. In particular, all three series of complexes show luminescence in the range 553-605 nm (Pt series), 620-640 nm (Re series) and 626-645 nm (Ru series) arising from the (3)MLCT state, with members of the Pt(II) series being the most strongly emissive with lifetimes of up to 500 ns and quantum yields of up to 6% in air-saturated CH(2)Cl(2) at room temperature. In the Re and Ru series there was clear evidence for inter-component energy-transfer processes in both directions between the (3)MLCT state of the metal centre and the singlet and triplet states of the pendant organic luminophores (naphthalene, pyrene, anthracene). For example the pyrene singlet is almost completely quenched by energy transfer to a Re-based MLCT excited state, which in turn is completely quenched by energy transfer to the lower-lying pyrene triplet state. For the analogous Ru(II) complexes the inter-component energy transfer is less effective, with (1)anthracene --> Ru((3)MLCT) energy transfer being absent, and Ru((3)MLCT)-->(3)anthracene energy transfer being incomplete. This is rationalised on the basis of a greater effective distance for energy transfer in the Ru(II) series, because the MLCT excited states are localised on the bpy ligands which are remote from the pendant aromatic group; in the Re series in contrast, the MLCT excited states involve the PB ligand to which the pendant aromatic group is directly attached, giving more efficient energy transfer.

Journal Article↗