Mapping the internal recognition surface of an octanuclear coordination cage using guest libraries

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 × 106 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 104–105 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

Amyloid precursor protein mRNA levels in the mononuclear blood cells of Alzheimer's and Down's patients

Amyloid precursor protein (APP) is expressed by many non-neural tissues and it is possible that over-expression of the APP gene in non-neural tissue is responsible for the deposition of amyloid β-protein in the brain and elsewhere. One possible source of β-protein is circulating mononuclear blood cells which have previously been shown to express APP. To test this hypothesis. RNA was isolated from the mononuclear blood cells of patients suffering from Alzheimer's disease (n = 27), Down's syndrome (n = 13), senile dementia non-Alzheimer type (n = 14) and from normal individuals (n = 48). The relative abundance of mRNA coding for different splicing variants of the amyloid precursor protein (APP) mRNA was measured using multiprobe oligonucleotide solution hybridisation (MOSH). There was no significant difference in APP mRNA levels between any of the groups. This indicates that Alzheimer's disease is not characterised by an increase in production of APP in circulating mononuclear blood cells

No evidence for a pseudoautosomal locus for schizophrenia. Linkage analysis of multiply affected families

Evidence for a pseudoautosomal locus for a schizophrenia susceptibility gene was sought by two forms of analysis of 25 multiply affected families. Firstly, in the sample as a whole there was an excess of same-sex over mixed-sex siblings compared with that expected. Secondly, linkage analysis was performed in six of the families. The genotypes were studied for DXYS14, a highly polymorphic marker in the telomeric pseudoautosomal region. No evidence for positive linkage was found with two-point analysis under eight different genetic models for the mode of transmission. A non-parametric, sibling-pair analysis also failed to detect linkage. Our findings provide no evidence for linkage within the pseudoautosomal region; same-sex concordance must arise from some other mechanism

Ferromagnetic Ni-II Discs

International audienceA family of planar disc-like hexa-, octa- and decametallic Ni-II complexes exhibit dominant ferromagnetic exchange. The deca- and octametallic clusters [Ni-10(II)(tmp)(2)(N-3)(8)(acac)(6)(MeOH)(6)] (1, H(3)tmp = 1,1,1-tris(hydroxymethyl)propane; acac = acetylacetonate) and [Ni-8(II)(thme)(2)(O2CPh)(4)(CI)(6)(MeCN)(6)(H2O)(2)] (2, H(3)thme = 1,1,1-tris(hydroxymethyl)ethane) represent rare examples of Ni-II-based single-molecule magnets, and [Ni-10(II)] (1) possesses the largest barrier to magnetisation reversal of any Ni-II single-molecule magnet to date