I. Introduction 61 II. Binding of Small Molecules to DNA 62 A. Covalent Binding 62 B. Reversible (Noncovalent) DNA-Binding Agents 65 III. DNA-Metal Ion Complexes 67 A. Platinum Complexes 70 B. Other Metal Ions 73 IV. DNA-Protein Complexes 74 A. Introduction 74 B. ESI-MS of DNA-Protein Complexes 76 C. ESI-MS Analysis of Proteolytic Products of DNA-Protein Complexes 79 D. ESI-MS of Ternary DNA-Protein-Ligand Complexes 80 V. Conclusions 80 Abbreviations 81 References 81 --Interactions of DNA with drugs, metal ions, and proteins are important in a wide variety of biological processes. With the advent of electrospray ionization (ESI) and matrix-assisted laser desorption ionization (MALDI), mass spectrometry (MS) is now a well-established tool for the characterization of the primary structures of biopolymers. The gentle nature of the ESI process, however, means that ESI-MS is also finding application for the study of noncovalent and other fragile biomolecular complexes. We outline here the progress, to date, in the use of ESI-MS for the study of noncovalent drug-DNA and protein-DNA complexes together with strategies that can be employed to examine the binding of small molecules and metal complexes to DNA. In the case of covalent complexes with DNA, sequence information can be derived from ESI-MS used in conjunction with tandem mass spectrometry (MS/MS) and/or enzymatic digestion. MS/MS can also be used to probe the relative binding affinities of drugs that bind to DNA via noncovalent interactions. Overall, the work in this area, to date has demonstrated that ESI-MS and MS/MS will prove to be valuable complements to other structural methods, offering advantages in terms of speed, specificity, and sensitivity. (c) 2001 John Wiley & Sons, Inc.

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The partial encapsulation of platinum(II)-based DNA intercalators of the type [Pt(5-Cl-phen)(ancillary ligand)](2+), where 5-Cl-phen is 5-chloro-1,10-phenanthroline and the ancillary ligand is ethylenediamine, (1S,2S)-diaminocyclohexane (S,S-dach) or (1R,2R)-diaminocyclohexane, within cucurbit[n]uril (CB[n], where n is 6, 7 or 8) has been examined by (1)H and (195)Pt NMR and mass spectrometry. For CB[7], the molecule encapsulates over the ancillary ligand of all metal complexes, whether this is ethylenediamine or diaminocyclohexane. For CB[8], encapsulation occurs over the sides of the 5-Cl-phen ligand at low [Pt(5-Cl-phen)(S,S-dach)](2+) (5CLSS) to CB[8] ratios (i.e. 0.25:1) but over the ancillary ligand at higher ratios (i.e. 2:1). For CB[6] binding, 5CLSS exhibits both portal and cavity binding, with the ancillary ligand displaying chemical shifts consistent with fast exchange kinetics on the NMR timescale for portal binding and slow exchange kinetics for cavity binding. Binding constants could not be determined using UV-vis, circular dichroism or fluorescence spectrophotometry, but a binding constant for binding of 5CLSS to CB[6] of approximately 10(5) M(-1) was determined using (1)H NMR. Finally, the effect of CB[n] encapsulation on the cytotoxicity of the metal complexes was examined using L1210 murine leukaemia cells in vitro growth inhibition assays. The cytotoxicity is highly dependent on both the metal complex and the CB[n] size, and whilst CB[7] and CB[8] generally decreased cytotoxicity, it was found that CB[6] increased the cyotoxicity of 5CLSS up to 2.5-fold.

The effect of preparation conditions and biopolymer dispersants on the The effect of preparation conditions and biopolymer dispersants on the properties of SWNT buckypapers properties of SWNT buckypapers

High power tip sonication was used to prepare dispersions containing multi-walled carbon nanotubes (MWNTs), or multi-walled carbon nanotubes functionalised with carboxylic acid groups (MWNT-COOH) or amine groups (MWNT-NH2). The dispersion of carbon nanotubes was facilitated by the presence of a surfactant (Triton X-100) or various macrocyclic ligands (derivatised porphyrin, phthalocyanine or calixarene) in the solution. Vacuum filtration of the dispersions afforded self-supporting membranes known as buckypapers. Microanalysis provided evidence for retention of the surfactant or macrocyclic ligands in the buckypapers, which were also characterised by measurement of their electrical conductivities (24±16 to 58±11 S/cm), contact angles (28±1° to 55±10°) and mechanical properties (tensile strengths varied between 1.6±0.7 and 13±2 MPa). The surface and internal morphologies of the buckypapers were similar to each other, which correlates with the lack of variation observed in their permeability's towards water. The ability of selected buckypapers to remove trace organic contaminants (TrOCs) was also examined. A buckypaper prepared using Triton X-100 as the dispersant showed more than 80% removal efficiency for 11 out of the 12 TrOCs investigated in this study. On the other hand, a buckypaper prepared from MWNTs and phthalocyaninetetrasulfonic acid exhibited lower removal efficiencies for these TrOCs, possibly due to their smaller specific surface area. KeywordsCarbon nanotubes, buckypapers, water permeability, trace organic contaminants, bisphenol A, GeoQuest S/cm), contact angles (28 ± 1 to 55 ± 10 ) and mechanical properties (tensile strengths varied between 1.6 ± 0.7 and 13 ± 2 MPa). The surface and internal morphologies of the buckypapers were similar to each other, which correlates with the lack of variation observed in their permeability's towards water. The ability of selected buckypapers to remove trace organic contaminants (TrOCs) was also examined. A buckypaper prepared using Triton X-100 as the dispersant showed more than 80% removal efficiency for 11 out of the 12 TrOCs investigated in this study. On the other hand, a buckypaper prepared from MWNTs and phthalocyaninetetrasulfonic acid exhibited lower removal efficiencies for these TrOCs, possibly due to their smaller specific surface area.

Over the course of the past decade, there has been growing interest in the development of different types of membranes composed of carbon nanotubes (CNTs), including buckypapers and composite materials, for an ever-widening range of filtration applications. This article provides an overview of how different types of CNT membranes are prepared and the results obtained from investigations into their suitability for different applications. The latter involve the removal of small particles from air samples, the filtration of aqueous solutions containing organic compounds and/or bacteria, and the separation of individual liquids present in mixtures. A growing number of reports have demonstrated that the incorporation of CNTs into composite membranes confers an improved resistance to fouling caused by biomacromolecules and bacteria. These results are discussed, along with evidence that demonstrates it is possible to further reduce fouling by taking advantage of the inherent conductivity of composite membranes containing CNTs, as well as by using different types of electrochemical stimuli.

Stereospecific sequential condensation of paraformaldehyde and propionaldehyde with a tripodal bis(triamine)cobalt(iii) template rapidly encapsulates the metal, and a subsequent facile reduction of imine functions gives an expanded cavity hexaazabicyclic cage system with unusual structural and chromophore electron properties, complemented by an exceptional stability and relatively fast Coii/ill electron exchange rates.

Electrospray ionisation (ESI) mass spectrometry was used to examine the reactions of the clinically used antiarthritic agent [Au(S2O3)2]3-, and AuPEt3Cl, a derivative of another clinically used agent auranofin, with human serum albumin (HSA) obtained from a human volunteer. Both compounds reacted readily with HSA to form complexes containing one or more covalently attached gold fragments. In the case of AuPEt3Cl, binding was accompanied by the loss of the chloride ligand, while for [Au(S2O3)2]3- the mass spectral data indicated binding of Au(S2O3) groups. Experiments performed using HSA with Cys34 blocked by reaction with iodoacetamide were consistent with reaction of both gold compounds with this amino acid. Separate blocking experiments using diethylpyrocarbonate and AuPEt3Cl also provided evidence for histidine residues acting as lower-affinity binding sites for this gold compound. ESI mass spectra of solutions containing [Au(S2O3)2]3- or [Au(CN)2]-, and HSA, provided evidence for the formation of protein complexes in which intact gold molecules were non-covalently bound. In the case of [Au(S2O3)2]3-, these non-covalent complexes proved to be transitory in nature. However, for [Au(CN)2]- a non-covalent complex containing a single gold molecule bound to HSA was found to be stable, and constituted the main adduct formed in solutions containing low-to-medium Au-to-HSA ratios. Evidence was also obtained for the formation of a covalent adduct in which a single Au(CN) moiety was bonded to Cys34 of the protein. AuPEt3Cl reacted to a much lower extent with HSA that had Cys34 modified by formation of a disulfide bond to added cysteine, than with unmodified HSA. This suggests that the extent of modification of the protein in vivo may have an important influence on the transport and bioavailability of gold antiarthritic drugs.