Intra- and intermolecular complexation in C6 monoazacoronand substituted cyclodextrins

The preparation of 6(A)-deoxy-6(A)-(6-(2-(1,4,7,10-tetraoxa-13-azacyclopentadecan-13-yl)acetamido)hexylamino)-alpha-cyclodextrin, 3, 6(A)-deoxy-6(A)-(6-(2-(1,4,7,10,13-pentaoxa-16-azacyclooctadecan-16-yl)acetamido)hexylamino)-alpha-cyclodextrin, 4, and their beta-cyclodextrin analogues, 5 and 6, are described. (1)H (600 MHz) ROESY NMR spectra of the C(6) substituted beta-cyclodextrins, 5 and 6, are consistent with the intramolecular complexation of their azacyclopentadecanyl- and azacyclooctadecanyl(acetamido)hexylamino substituents in the beta-cyclodextrin annulus in D(2)O at pD = 8.5 whereas those of their alpha-cyclodextrin analogues, 3 and 4 are not complexed in the alpha-cyclodextrin annulus. This is attributed to the monoazacoronand components of the substituents being able to pass through the beta-cyclodextrin annulus whereas they are too large to pass through the alpha-cyclodextrin annulus. However, the substituents of 3 and 4 are intermolecularly complexed by beta-cyclodextrin to form pseudo [2]-rotaxanes. Metallocyclodextrins are formed by 5 through complexation by the monoazacoronand substituent component for which log (K/dm(3) mol(-1))= <2, 6.34 and 5.38 for Ca(2+), Zn(2+) and La(3+), respectively, in aqueous solution at 298.2 K and I= 0.10 mol dm(-3)(NEt(4)ClO(4)).     

Recovery of 177Lu from Irradiated HfO2 Targets for Nuclear Medicine Purposes

A new method of production of one of the most widely used isotopes in nuclear medicine, ¹⁷⁷Lu, with high chemical purity was developed; this method includes irradiation of the HfO₂ target with bremsstrahlung photons. The irradiated target was dissolved in HF and then diluted and placed onto a column filled with LN resin. Quantitative sorption of ¹⁷⁷Lu could be observed during this process. The column later was rinsed with the mixture of 0.1 M HF and 1 M HNO₃ and then 2 M HNO₃ to remove impurities. Quantitative desorption of ¹⁷⁷Lu was achieved by using 6 M HNO₃. The developed method of ¹⁷⁷Lu production ensures high purification of this isotope from macroquantities of hafnium and zirconium and radioactive impurities of carrier-free yttrium. The content of ^177mLu in ¹⁷⁷Lu in photonuclear production was determined. Due to high chemical and radionuclide purity, ¹⁷⁷Lu obtained by the developed method can be used in nuclear medicine.     

Acid–Base Equilibrium and Self-Association in Relation to High Antitumor Activity of Selected Unsymmetrical Bisacridines Established by Extensive Chemometric Analysis

Unsymmetrical bisacridines (UAs) represent a novel class of anticancer agents previously synthesized by our group. Our recent studies have demonstrated their high antitumor potential against multiple cancer cell lines and human tumor xenografts in nude mice. At the cellular level, these compounds affected 3D cancer spheroid growth and their cellular uptake was selectively modulated by quantum dots. UAs were shown to undergo metabolic transformations in vitro and in tumor cells. However, the physicochemical properties of UAs, which could possibly affect their interactions with molecular targets, remain unknown. Therefore, we selected four highly active UAs for the assessment of physicochemical parameters under various pH conditions. We determined the compounds’ pK_a dissociation constants as well as their potential to self-associate. Both parameters were determined by detailed and complex chemometric analysis of UV-Vis spectra supported by nuclear magnetic resonance (NMR) spectroscopy. The obtained results indicate that general molecular properties of UAs in aqueous media, including their protonation state, self-association ratio, and solubility, are strongly pH-dependent, particularly in the physiological pH range of 6 to 8. In conclusion, we describe the detailed physicochemical characteristics of UAs, which might contribute to their selectivity towards tumour cells as opposed to their effect on normal cells.     

Novel C60 Fullerenol-Gentamicin Conjugate–Physicochemical Characterization and Evaluation of Antibacterial and Cytotoxic Properties

This study aimed to develop, characterize, and evaluate antibacterial and cytotoxic properties of novel fullerene derivative composed of C₆₀ fullerenol and standard aminoglycoside antibiotic–gentamicin (C₆₀ fullerenol-gentamicin conjugate). The successful introduction of gentamicin to fullerenol was confirmed by X-ray photoelectron spectroscopy which together with thermogravimetric and spectroscopic analysis revealing the formula of the composition as C₆₀(OH)₁₂(GLYMO)₁₁(Gentamicin)_0.8. The dynamic light scattering (DLS) revealed that conjugate possessed ability to form agglomerates in water (size around 115 nm), while Zeta potential measurements demonstrated that such agglomerates possessed neutral character. In vitro biological assays indicated that obtained C₆₀ fullerenol-gentamicin conjugate possessed the same antibacterial activity as standard gentamicin against Staphylococcus aureus, Staphylococcus epidermidis, Pseudomonas aeruginosa, and Escherichia coli, which proves that combination of fullerenol with gentamicin does not cause the loss of antibacterial activity of antibiotic. Moreover, cytotoxicity assessment demonstrated that obtained fullerenol-gentamicin derivative did not decrease viability of normal human fibroblasts (model eukaryotic cells) compared to control fibroblasts. Thus, taking into account all of the results, it can be stated that this research presents effective method to fabricate C₆₀ fullerenol-gentamicin conjugate and proves that such derivative possesses desired antibacterial properties without unfavorable cytotoxic effects towards eukaryotic cells in vitro. These promising preliminary results indicate that obtained C₆₀ fullerenol-gentamicin conjugate could have biomedical potential. It may be presumed that obtained fullerenol may be used as an effective carrier for antibiotic, and developed fullerenol-gentamicin conjugate may be apply locally (i.e., at the wound site). Moreover, in future we will evaluate possibility of its applications in inter alia tissue engineering, namely as a component of wound dressings and implantable biomaterials.     

Chiral and water‐soluble poly(2‐oxazoline)s

We describe the synthesis and characterization of the first water‐soluble and chiral poly(2,4‐disubstituted‐2‐oxazoline)s. While poly(2,4‐dimethyl‐2‐oxazoline)s are water soluble up to 100 °C, aqueous solutions of poly(2‐ethyl‐4‐methly‐2‐oxazoline) exhibit a lower critical solution temperature. This is discussed in context with its constitutional isomers poly(2‐oxazoline)s and poly(2‐oxazine)s. Circular dichroism spectroscopy revealed strong Cotton effects, which are also responsive to temperature in aqueous solution. It is therefore hypothesized that structures, comparable to polyproline helices, are formed in aqueous solution. In contrast to polyproline, poly(2,4‐disubstituted‐2‐oxazoline)s are highly water soluble and therefore represent very interesting pseudo‐polypeptides that may be useful to develop responsive biomimetic biomaterials. © 2012 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem, 2013     

Insensitivity of leptogenesis with flavor effects to low energy leptonic CP violation

If the baryon asymmetry of the Universe is produced by leptogenesis, CP violation is required in the lepton sector. In the seesaw extension of the standard model with three hierarchical right-handed neutrinos, we show that the baryon asymmetry is insensitive to the Pontecorvo-Maki-Nagakawa-Sakata phases: thermal leptogenesis can work for any value of the observable phases. This result was well known when there were no flavor effects in leptogenesis; we show that it remains true when flavor effects are included.     

A comparison of T2*-weighted magnitude and phase imaging for measuring the arterial input function in the rat aorta following intravenous injection of gadolinium contrast agent

The arterial input function (AIF) is important for quantitative MR imaging perfusion experiments employing Gd contrast agents. This study compared the accuracy of T(2)*-weighted magnitude and phase imaging for noninvasive measurement of the AIF in the rat aorta. Twenty-eight in vivo experiments were performed involving simultaneous arterial blood sampling and MR imaging following Gd injection. In vitro experiments were also performed to confirm the in vivo results. At 1.89 T and TE=3 ms, the relationship between changes in 1/T(2)* in blood (estimated from MR signal magnitude) and Gd concentration ([Gd]) was measured to be approximately 19 s(-1) mM(-1), while that between phase and [Gd] was approximately 0.19 rad mM(-1). Both of these values are consistent with previously published results. The in vivo phase data had approximately half as much scatter with respect to [Gd] than the in vivo magnitude data (r(2)=.34 vs. r(2)=.17, respectively). This is likely due to the fact that the estimated change in 1/T(2)* is more sensitive than the phase to a variety of factors such as partial volume effects and T(1) weighting. Therefore, this study indicates that phase imaging may be a preferred method for measuring the AIF in the rat aorta compared to T(2)*-weighted magnitude imaging.     

Investigating generation mechanisms of tyre/road noise by speed exponent analysis

The purpose of this study is to clarify the influence of air-pumping related noise sources on typical tyre/road noise. The aim is to increase the understanding of noise generation mechanisms and catalyse the development of existing tyre/road noise simulation tools. The speed dependency of measured and simulated tyre/road noise is analysed and the results show that a large part of the noise can be explained by a high speed exponent traditionally connected with air-pumping mechanisms. Surprisingly, this is also the case for rough road surfaces which are expected to mainly generate noise by tyre vibrations. It is also found that vehicle wind noise may have a strong influence on the pass-by noise and care must be taken when analysing measurement data of quiet tyre/road combinations. Even simulated tyre/road noise shows higher speed exponents than what is anticipated without the inclusion of any type of air-pumping mechanism in the model. It is concluded that it is unfeasible to separate noise created by tyre vibrations from noise created by air-pumping with a speed exponent analysis due to the overlap in the speed exponents connected with the different generation mechanisms.     

Rotationally invariant bipartite states and bound entanglement

We consider rotationally invariant states in CN₁⊗CN₂${\mathbb{C}}^{N_1}\otimes {\mathbb{C}}^{N_2}$ Hilbert space with even N₁?4$N_1?4$ and arbitrary N₂?N₁$N_2?N_1$, and show that in such case there always exist states which are inseparable and remain positive after partial transposition, and thus the PPT criterion does not suffice to prove separability in such systems. We demonstrate it applying a map developed recently by Breuer [H.-P. Breuer, Phys. Rev. Lett. 97 (2006) 080501] to states that remain invariant after partial time reversal.