Entropy-Enthalpy Compensation May Be a Useful Interpretation Tool for Complex Systems Like Protein-DNA Complexes: An Appeal to Experimentalists

In various chemical systems enthalpy-entropy compensation (EEC) is a well-known rule of behavior, although the physical roots of it are still not completely understood. It has been frequently questioned whether EEC is a truly physical phenomenon or a coincidence due to trivial mathematical connections between statistical-mechanical parameters - or even simpler: A phantom effect resulting from the misinterpretation of experimental data. Here, we review EEC from a new standpoint using the notion of correlation which is essential for the method of factor analysis, but is not conventional in physics and chemistry. We conclude that the EEC may be rationalized in terms of hidden (not directly measurable with the help of the current experimental set-up) but physically real factors, implying a Carnot-cycle model in which a micro-phase transition (MPT) plays a crucial role. Examples of such MPTs underlying physically valid EEC should be typically cooperative processes in supramolecular aggregates, like changes of structured water at hydrophobic surfaces, conformational transitions upon ligand-biopolymer binding, and so on, so forth. The MPT notion could help rationalize the occurrence of EEC in connection with hydration and folding of proteins,enzymatic reactions, functioning of molecular motors, DNA de- and rehybridization, as well as similar phenomena.Comment: 8 pages, 2 Figures, Submitted for publicatio

Pendulum as a model system for driven rotation in molecular nanoscale machines

We suggest a ratchet mechanism of rotatory (or translatory) motion of a Brownian rotator (or a particle) in a spatially symmetric periodic potential. The asymmetry that drives the ratchet motion is due to a special sequence of activation of catalytic sites arranged in space circularly and periodically. A pendulum driven by short impulses at its stable equilibrium point is shown to be a simple mechanical model which can be constructed easily and used for visual observation of the ratchet rotation. A possible application of this mechanism in nanotechnology is briefly discussed

Thermally regulated reversible formation of vesicle-like assemblies by hexaproline amphiphiles

Peptides composed of hexaproline and glutamic acid (P6E) or lysine (P6K) as C-terminal units show thermally promoted aggregation, affording vesicle-like assemblies upon heating to 80 ºC. The aggregation is analyzed by dynamic light scattering (DLS), with number averaged diameters of ca. 600 and 300 nm respectively for P6E and P6K. NMR studies reveal that upon heating the amount of NMR-visible species is reduced to ca. 50% and that an important conformational change is experienced by the molecules in solution. Circular dichroism (CD) shows that at 20º C the peptides present a polyproline II (PP-II) conformation which is disorganized upon heating. Scanning electron microscopy for samples which were fast frozen at 80 ºC reveals vesicle-like assemblies. Using pyrene as a fluorescence probe, a critical aggregation concentration of ca. 30 m was estimated for P6E while that of P6K was above 0.6 mM. The aggregation process is found to be fully reversible and could serve as a basis for development of stimuli responsive carriers

ValiDichro: a website for validating and quality control of protein circular dichroism spectra

Circular dichroism (CD) spectroscopy is widely used in structural biology as a technique for examining the structure, folding and conformational changes of proteins. A new server, ValiDichro, has been developed for checking the quality and validity of CD spectral data and metadata, both as an aid to data collection and processing and as a validation procedure for spectra to be included in publications. ValiDichro currently includes 25 tests for data completeness, consistency and quality. For each test that is done, not only is a validation report produced, but the user is also provided with suggestions for correcting or improving the data. The ValiDichro server is freely available at http://valispec.cryst.bbk.ac.uk/circularDichroism/ValiDichro/upload.html

Ecosystem Services and Opportunity Costs Shift Spatial Priorities for Conserving Forest Biodiversity

Inclusion of spatially explicit information on ecosystem services in conservation planning is a fairly new practice. This study analyses how the incorporation of ecosystem services as conservation features can affect conservation of forest biodiversity and how different opportunity cost constraints can change spatial priorities for conservation. We created spatially explicit cost-effective conservation scenarios for 59 forest biodiversity features and five ecosystem services in the county of Telemark (Norway) with the help of the heuristic optimisation planning software, Marxan with Zones. We combined a mix of conservation instruments where forestry is either completely (non-use zone) or partially restricted (partial use zone). Opportunity costs were measured in terms of foregone timber harvest, an important provisioning service in Telemark. Including a number of ecosystem services shifted priority conservation sites compared to a case where only biodiversity was considered, and increased the area of both the partial (+36.2%) and the non-use zone (+3.2%). Furthermore, opportunity costs increased (+6.6%), which suggests that ecosystem services may not be a side-benefit of biodiversity conservation in this area. Opportunity cost levels were systematically changed to analyse their effect on spatial conservation priorities. Conservation of biodiversity and ecosystem services trades off against timber harvest. Currently designated nature reserves and landscape protection areas achieve a very low proportion (9.1%) of the conservation targets we set in our scenario, which illustrates the high importance given to timber production at present. A trade-off curve indicated that large marginal increases in conservation target achievement are possible when the budget for conservation is increased. Forty percent of the maximum hypothetical opportunity costs would yield an average conservation target achievement of 79%

Nanosheet formation by an anionic surfactant-like peptide and modulation of self-assembly through ionic complexation

The surfactant-like peptide (Ala)6-(Asp) (A6D) is shown to self-assemble into ultrathin (3 nm thick) nanosheets in aqueous solution above a critical aggregation concentration. A combination of circular dichroism and FTIR spectroscopy and X-ray diffraction shows that the nanosheets comprise interdigitated bilayers of the peptide with β-sheet conformation. The self-assembly can be modulated by addition of hexamethylenediamine which is expected to interact with the anionic C terminus (and C-terminal D residue) of the peptide. Multiple ordered nanostructures can be accessed depending on the amount of added diamine. Nanosheet and bicontinuous network structures were observed using cryogenic-TEM and small-angle X-ray scattering. Addition of hexamethylenediamine at a sufficiently large molar ratio leads to disruption of the ordered nanostructure and the formation of a solution of A6D–diamine molecular complexes with highly charged end groups. The multiple acid-functionalized nanostructures that are accessible in this system are expected to have many applications in the fabrication of new nanomaterials

Ruthenium polypyridyl complexes and their modes of interaction with DNA : is there a correlation between these interactions and the antitumor activity of the compounds?

Various interaction modes between a group of six ruthenium polypyridyl complexes and DNA have been studied using a number of spectroscopic techniques. Five mononuclear species were selected with formula [Ru(tpy) L1L2](2-n)?, and one closely related dinuclear cation of formula [{Ru(apy)(tpy)}2{l-H2N(CH2)6NH2}]4?. The ligand tpy is 2,20:60,200-terpyridine and the ligand L1 is a bidentate ligand, namely, apy (2,20-azobispyridine), 2-phenylazopyridine, or 2-phenylpyridinylmethylene amine. The ligand L2 is a labile monodentate ligand, being Cl-, H2O, or CH3CN. All six species containing a labile L2 were found to be able to coordinate to the DNA model base 9-ethylguanine by 1H NMR and mass spectrometry. The dinuclear cationic species, which has no positions available for coordination to a DNA base, was studied for comparison purposes. The interactions between a selection of four representative complexes and calf-thymus DNA were studied by circular and linear dichroism. To explore a possible relation between DNA-binding ability and toxicity, all compounds were screened for anticancer activity in a variety of cancer cell lines, showing in some cases an activity which is comparable to that of cisplatin. Comparison of the details of the compound structures, their DNA binding, and their toxicity allows the exploration of structure–activity relationships that might be used to guide optimization of the activity of agents of this class of compounds

Self-assembly of the toll-like receptor agonist macrophage-activating lipopeptide MALP-2 and of its constituent peptide

The self-assembly of the macrophage-activating lipopeptide MALP-2 in aqueous solution has been investigated and is compared to that of the constituent peptide GNNDESNISFKEK. MALP-2 is a toll-like receptor agonist lipopeptide with diverse potential biomedical applications and its self-assembly has not previously been examined. It is found to self-assemble, above a critical aggregation concentration (cac), into remarkable “fibre raft” structures, based on lateral aggregation of β-sheet based bilayer tapes. Peptide GNNDESNISFKEK also forms β-sheet structures above a cac, although the morphology is distinct, comprising highly extended and twisted tape structures. A detailed insight into the molecular packing within the MALP-2 raft and GNNDESNISFKEK nanotape structures is obtained through X-ray diffraction and small-angle X-ray scattering. These results point to the significant influence of the attached lipid chains on the self-assembly motif, which lead to the raft structure for the lipopeptide assemblies

Effects of chirality on the intracellular localization of binuclear ruthenium(II) polypyridyl complexes

Interest in binuclear ruthenium(II) polypyridyl complexes as luminescent cellular imaging agents and for biomedical applications is increasing rapidly. We have investigated the cellular localization, uptake, and biomolecular interactions of the pure enantiomers of two structural isomers of [μ-bipb(phen)4Ru2]4+ (bipb is bis(imidazo[4,5-f]-1,10-phenanthrolin-2-yl)benzene and phen is 1,10-phenanthroline) using confocal laser scanning microscopy, emission spectroscopy, and linear dichroism. Both complexes display distinct enantiomeric differences in the staining pattern of fixed cells, which are concluded to arise from chiral discrimination in the binding to intracellular components. Uptake of complexes in live cells is efficient and nontoxic at 5 μM, and occurs through an energy-dependent mechanism. No differences in uptake are observed between the structural isomers or the enantiomers, suggesting that the interactions triggering uptake are rather insensitive to structural variations. Altogether, these findings show that the complexes investigated are promising for future applications as cellular imaging probes. In addition, linear dichroism shows that the complexes exhibit DNA-condensing properties, making them interesting as potential gene delivery vectors