A photoinduced pH jump applied to drug release from cucurbit[7]uril

A proof-of-principle for the application of a photoinduced pH jump for delivery of the Hoechst 33258 drug by disassembly of its host-guest complex with cucurbit[7]uril is described

Release of High-Energy Water as an Essential Driving Force for the High-Affinity Binding of Cucurbit[<i>n</i>]urils

Molecular dynamics simulations and isothermal titration calorimetry (ITC) experiments with neutral guests illustrate that the release of high-energy water from the cavity of cucurbit­[<i>n</i>]­uril (CB<i>n</i>) macrocycles is a major determinant for guest binding in aqueous solutions. The energy of the individual encapsulated water molecules decreases with increasing cavity size, because larger cavities allow for the formation of more stable H-bonded networks. Conversely, the total energy of internal water increases with the cavity size because the absolute number of water molecules increases. For CB7, which has emerged as an ultrahigh affinity binder, these counteracting effects result in a maximum energy gain through a complete removal of water molecules from the cavity. A new design criterion for aqueous synthetic receptors has therefore emerged, which is the optimization of the size of cavities and binding pockets with respect to the energy and number of residing water molecules

Inclusion of neutral guests by water-soluble macrocyclic hosts – a comparative thermodynamic investigation with cyclodextrins, calixarenes and cucurbiturils

<p>The driving forces of association between three different families of macrocycles as hosts, namely cyclodextrins (<i>α</i>-, <i>β</i>-, and <i>γ</i>-), <i>p</i>-sulfonatocalix[<i>n</i>]arenes (<i>n</i> = 4–6) as well as cucurbit[<i>n</i>]urils (<i>n</i> = 6–8), and three different bicyclic azoalkane homologues as guests, namely 2,3-diazabicyclo[2.2.1]hept-2-ene (DBH), 2,3-diazabicyclo[2.2.2]oct-2-ene (DBO) as well as 2,3-diazabicyclo[2.2.3]non-2-ene (DBN), were examined by means of calorimetric titrations, NMR spectroscopy and molecular dynamics simulation, all in aqueous solution. The small, spherical and uncharged guests preferably bind inside the cavities of the medium sized hosts. The inclusion complexation by <i>β</i>-cyclodextrin and <i>p</i>-sulfonatocalix[4]arene shows medium binding affinities (millimolar), while cucurbit[7]uril macrocycle shows very strong binding (micromolar). For all types of macrocycles, the complex formation is enthalpically driven (Δ<i>H</i>° < 0), accompanied by slightly unfavourable entropy changes (Δ<i>S</i>° < 0). The results are discussed in terms of the flexibility of the hosts, the hydrophobic character of their cavities and the release of high-energy water upon binding, and generalised by including two additional guests, the ketones cyclopentanone and (+)-camphor.</p

YKL-40 – A NEW DIAGNOSTIC BIOMARCER FOR BENIGN BREAST DISEASES AND BREAST CANCER

Benign breast diseases encompass a wide spectrum of lesions, which raise a lot of questions about their classification, diagnosis, prognosis and surgical treatment. The aim of this study is to measure the serum level of YKL-40 in cases of different groups of benign breast diseases, to compare it to the level of healthy women as well as to those with breast cancer and to examine its tissue expression after surgical treatment. We use it as a diagnostic marker and as a criterion for differential diagnosis.Forty nine (49) patients with benign breast diseases and twenty (20) patients with breast cancer were examined. All of them had their serum level of YKL-40 measured preoperatively and its tissue expression examined immunohystochemically after the surgical intervention. There were significant differences in both concentration and tissue expression of this marker in patients with different groups of benign breast diseases and breast cancer. YKL-40 can be an important biomarker in the diagnosis and differential diagnosis of breast diseases