A water-soluble cubic coordination cage (H w) has been prepared, which is isostructural with a previously reported organic-soluble cage (H) apart from the hydroxy groups on the external surface which render it water-soluble. These two cages act as hosts for small organic molecules which bind via a combination of (i) hydrogen-bonding interactions with specific sites on the internal surface of the cages; (ii) nonpolar interactions such as aromatic and van der Waals interactions between aromatic rings in the guest and the cage internal surface; and (iii) solvophobic interactions. By comparing DG values for guest binding in water (using H w) and MeCN (using H), and using pairs of related guests that differ in the presence or absence of an aromatic ring substituent, it is possible to construct thermodynamic cycles that allow quantification of the solvophobic contribution to binding. Specifically, this is the difference between the solvophobic contributions to DG in water and MeCN associated with desolvation of both guest and the internal surface of the cage when complexation occurs. A highly consistent value of ca. À10 kJ mol À1 is determined for this solvophobic contribution to DG associated with the aromatic ring in water compared to MeCN, which correlates very well with what would be expected based on the free energy changes associated with transfer of toluene from MeCN to water. Thus, all three contributions to guest binding listed above can be separately quantified. The ability to prepare related pairs of guests with the presence or absence of a wide range of substituents provides a potentially general way to quantify the solvophobic contributions to guest binding of these substituents.

No abstract

Size and shape criteria for guest binding inside the cavity of an octanuclear cubic coordination cage in water have been established using a new fluorescence displacement assay to quantify guest binding. For aliphatic cyclic ketones of increasing size (from C5 to C11), there is a linear relationship between ΔG for guest binding and the guest's surface area: the change in ΔG for binding is 0.3 kJ mol(-1) Å(-2), corresponding to 5 kJ mol(-1) for each additional CH2 group in the guest, in good agreement with expectations based on hydrophobic desolvation. The highest association constant is K = 1.2 × 10(6) M(-1) for cycloundecanone, whose volume is approximately 50% of the cavity volume; for larger C12 and C13 cyclic ketones, the association constant progressively decreases as the guests become too large. For a series of C10 aliphatic ketones differing in shape but not size, ΔG for guest binding showed no correlation with surface area. These guests are close to the volume limit of the cavity (cf. Rebek's 55% rule), so the association constant is sensitive to shape complementarity, with small changes in guest structure resulting in large changes in binding affinity. The most flexible members of this series (linear aliphatic ketones) did not bind, whereas the more preorganized cyclic ketones all have association constants of 10(4)-10(5) M(-1). A crystal structure of the cage·cycloundecanone complex shows that the guest carbonyl oxygen is directed into a binding pocket defined by a convergent set of CH groups, which act as weak hydrogen-bond donors, and also shows close contacts between the exterior surface of the disc-shaped guest and the interior surface of the pseudospherical cage cavity despite the slight mismatch in shape.

Introduction: Diabetic retinopathy (DR) is the leading cause of vision loss in the working age population of the developed world. DR encompasses a complex pathology, and one that is reflected in the variety of currently available treatments, which include laser photocoagulation, glucocorticoids, vitrectomy and agents which neutralize vascular endothelial growth factor (VEGF). Whilst these options demonstrate modest clinical benefits, none is yet to fully attenuate clinical progression or reverse damage to the retina.This has led to an interest in developing novel therapies for the condition, such as mediators of angiopoietin signaling axes, immunosuppressants, nonsteroidal anti-inflammatory drugs (NSAIDs), oxidative stress inhibitors and vitriol viscosity inhibitors. Further, preclinical research suggests that gene therapy treatment for DR could provide significant benefits over existing treatments options.Areas covered: Here we review the pathophysiology of DR and provide an overview of currently available treatments. We then outline recent advances made towards improved patient outcomes and highlight the potential of the gene therapy paradigm to revolutionize DR management.Expert opinion: Whilst significant progress has been made towards our understanding of DR, further research is required to enable the development of a detailed spatiotemporal model of the disease. In addition, we hope that improvements in our knowledge of the condition facilitate therapeutic innovations that continue to address unmet medical need and improve patient outcomes, with a focus on the development of targeted medicines.

The host-guest chemistry of the octanuclear cubic coordination cage [Co(8)L(12)](16+) (where L is a bridging ligand containing two chelating pyrazolyl-pyridine units connected to a central naphthalene-1,5-diyl spacer via methylene "hinges") has been investigated in detail by (1)H NMR spectroscopy. The cage encloses a cavity of volume of ca. 400 Å(3), which is accessible through 4 Å diameter portals in the centers of the cube faces. The paramagnetism of the cage eliminates overlap of NMR signals by dispersing them over a range of ca. 200 ppm, making changes of specific signals easy to observe, and also results in large complexation-induced shifts of bound guests. The cage, in CD(3)CN solution, acts as a remarkably size- and shape-selective host for small organic guests such as coumarin (K = 78 M(-1)) and other bicyclic molecules of comparable size and shape such as isoquinoline-N-oxide (K = 2100 M(-1)). Binding arises from two independent recognition elements, which have been separately quantified. These are (i) a polar component arising from interaction of the H-bond accepting O atom of the guest with a convergent group of CH protons inside the cavity that lie close to a fac tris-chelate metal center and are therefore in a region of high electrostatic potential; and (ii) an additional component arising from the second aromatic ring (aromatic/van der Waals interactions with the interior surface of the cage and/or solvophobic interactions). The strength of the first component varies linearly with the H-bond-accepting ability of the guest; the second component is fixed at approximately 10 kJ mol(-1). We have also used (1)H-(1)H exchange spectroscopy (EXSY) experiments to analyze semiquantitatively two distinct dynamic processes, viz. movement of the guest into and out of the cavity and tumbling of the guest inside the host cavity. Depending on the size of the guest and the position of substituents, the rates of these processes can vary substantially, and the rates of processes that afford observable cross-peaks in EXSY spectra (e.g., between free and bound guest in some cases; between different conformers of a specific host·guest complex in others) can be narrowed down to a specific time window. Overall, the paramagnetism of the host cage has allowed an exceptionally detailed analysis of the kinetics and thermodynamics of its host-guest behavior.

2423 the C,, type. 490. The Xtructure of the Phosphonitrilic Halides.

A new strategy to effect photoinduced control over molecular self-assembly is reported. This strategy uses the reversible trans-cis photoisomerization of a novel azobenzene system, where the trans- and cis-forms self-assemble into dramatically different higher-order structures. The trans-azobenzene form of this molecule associates into infinite hydrogen-bonded linear tapes, while the cis-azobenzene form undergoes hydrogen-bonded self-assembly into cyclic tetramers. This results in a second level of association, where the cis-hydrogen-bonded supramolecular cycles ultimately form long, rod-like aggregates through stacking interactions.

No abstract