Recognition of thymine and related nucleosides by a Zn(II)-cyclen complex bearing a ferrocenyl pendant

A cyclen derivative bearing a ferrocenyl arm (L) and a series of its ZnII complexes [ZnL(OH2)][ClO4]2 (C1), [ZnL(OH)][ClO4] (C2), and [ZnL(Cl)][ClO4].CH3CN (C3) (cyclen = 1,4,7,10-tetraazacyclododecane, L = 1-(ferrocenemethyl)-1,4,7,10-tetraazacyclododecane) have been prepared and characterized spectroscopically. An X-ray structure determination confirmed the formation of complex C1 and revealed that the coordinated water participates in hydrogen bonding with the perchlorate counter ions. The pKa value for deprotonation of the water molecule determined by potentiometric titration was found to be 7.36 +/- 0.09 at 25 degrees C and I = 0.1 (KNO3). The possibility of using complex C1 as a potential sensor for thymine derivatives in aqueous solution has been examined. Shifts in the 1H and 13C NMR resonances showed the binding occurred with thymine (T) and two thymine derivatives, thymidine (dT) and thymidine 5'-monophosphate (TMP2-). Significant shifts of the nuC=O and nuC=C vibrations of the thymine derivatives were also observed via IR spectroscopy upon complexation with the receptor. The thymine adduct, [ZnL(thymine anion)][ClO4].2H2O (C4), has been crystallized and characterized. The X-ray structure of C4 confirmed the thymine binding to the receptor, and the short Zn-N(thymine) distance of 1.975(5) A indicated clearly that the ferrocenyl arm does not affect the complexation of the DNA base. In contrast to the large spectral changes, electrochemical studies showed a small shift of the reversible potential of the redox couple Fc+/Fc (Fc = ferrocene) and subtle changes in voltammetry upon the addition of an excess of dT, TMP2-, and guanine (dG) at physiological pH, indicating the level of interaction is similar in both Fc and Fc+ forms.     

Products of hydrolysis of (ferrocenylmethyl)trimethylammonium iodide: Synthesis of hydroxymethylferrocene and bis(ferrocenylmethyl) ether

The attempted coupling of (ferrocenylmethyl)trimethylammonium iodide (1) with 1,4,7-(triformyl)-1,4,7,10-tetraazacyclododecane (2) in water led to the formation of the expected compound 1-(ferrocenemethyl)-4,7,10-(triformyl)-1,4,7,10-tetraazacyclododecane (3). In addition, hydrolysis of the ferrocenyl precursor 1 led to the formation of two other known compounds, hydroxymethylferrocene (4) and bis(ferrocenylmethyl) ether (5). An X-ray crystal structure determination of 4 revealed the presence of H-bonding between the hydroxyl groups of one molecule of 4 and the oxygen atom of an adjacent molecule resulting in a left-handed helical chain of molecules lying along the b-axis direction. The O?O distances are significantly shorter than those found in previously reported structures of hydroxymethylferrocene derivatives indicative of moderate strength H-bonding interactions. In the structure of 5, the orientation of the ferrocenyl groups are staggered relative to a vector comprising the two carbons of the C-O-C linker.     

On a Model for Fires in Tunnel Network Structures

A one dimensional model to describe the dynamics of tunnelfires is used to model tunnel network structures. The corresponding conditions at the nodes are formulated. A numerical methods is presented. (© 2004 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)     

On Closure Conditions for the Moment Equations of a Bipolar Kinetic Model

We consider a bipolar kinetic model for charged media. In certain scalings the Debye length or the relaxation time are small. In addition different time scales are considered. These can be used in order to close the corresponding moment equations and leads to a (closed) set of macroscopic equations. We show three different scalings and obtain three completely different sets of macroscopic equations.     

Synthesis, characterisation and bioimaging of a fluorescent rhenium-containing PNA bioconjugate

A new rhenium tricarbonyl complex of a bis(quinoline)-derived ligand (2-azido-N,N-bis((quinolin-2-yl)methyl)ethanamine, L-N(3)), namely [Re(CO)(3)(L-N(3))]Br was synthesized and characterized in-depth, including by X-ray crystallography. [Re(CO)(3)(L-N(3))]Br exhibits a strong UV absorbance in the range 300-400 nm with a maximum at 322 nm, and upon photoexcitation, shows two distinct emission bands at about 430 and 560 nm in various solvents (water, ethylene glycol). [Re(CO)(3)(L-N(3))]Br could be conjugated, on a solid phase, to a peptide nucleic acid (PNA) oligomer using the copper(I)-catalyzed azide-alkyne cycloaddition reaction (Cu-AAC, "click" chemistry) and an alkyne-containing PNA building block to give Re-PNA. It was demonstrated that upon hybridisation with a complementary DNA strand (DNA), the position of the maxima and emission intensity for the hybrid Re-PNA·DNA remained mainly unchanged compared to those of the single strand Re-PNA. The rhenium-containing PNA oligomer Re-PNA could be then mediated in living cells where they have been shown to be non-toxic contrary to the general notion that organometallic compounds are usually unstable under physiological conditions and/or cytotoxic. Furthermore, Re-PNA could be detected in living cells using fluorescent microscopy.     

Small organometallic compounds as antibacterial agents

The emergence of bacterial resistance to commercial antibiotics is an issue of global importance. During the last two decades, the number of antibacterial agents that have been discovered and introduced into the market has steadily declined and failed to meet the challenges posed by rapidly increasing resistance of the pathogens against common antibacterial drugs. The development of new classes of compounds to control the virulence of the pathogens is therefore urgently required. This perspective describes the historical development in brief and recent advances on the preparation of small organometallic compounds as new classes of antibacterial agents with potential for clinical development.     

Diffusion and viscosity of liquid tin: Green-Kubo relationship-based calculations from molecular dynamics simulations

Molecular dynamics (MD) simulations of liquid tin between its melting point and 1600 °C have been performed in order to interpret and discuss the ionic structure. The interactions between ions are described by a new accurate pair potential built within the pseudopotential formalism and the linear response theory. The calculated structure factor that reflects the main information on the local atomic order in liquids is compared to diffraction measurements. Having some confidence in the ability of this pair potential to give a good representation of the atomic structure, we then focused our attention on the investigation of the atomic transport properties through the MD computations of the velocity autocorrelation function and stress autocorrelation function. Using the Green-Kubo formula (for the first time to our knowledge for liquid tin) we determine the macroscopic transport properties from the corresponding microscopic time autocorrelation functions. The selfdiffusion coefficient and the shear viscosity as functions of temperature are found to be in good agreement with the experimental data.     

Multidisciplinary Preclinical Investigations on Three Oxamniquine Analogues as New Drug Candidates for Schistosomiasis**

Schistosomiasis is a disease of poverty affecting millions of people. Praziquantel (PZQ), with its strengths and weaknesses, is the only treatment available. We previously reported findings on three lead compounds derived from oxamniquine (OXA), an old antischistosomal drug: ferrocene-containing (Fc-CH₂-OXA), ruthenocene-containing (Rc-CH₂-OXA) and benzene-containing (Ph-CH₂-OXA) OXA derivatives. These derivatives showed excellent in vitro activity against both Schistosoma mansoni larvae and adult worms and S. haematobium adult worms, and were also active in vivo against adult S. mansoni. Encouraged by these promising results, we conducted additional in-depth preclinical studies and report in this investigation on metabolic stability studies, in vivo studies on S. haematobium and juvenile S. mansoni, computational simulations, and formulation development. Molecular dynamics simulations supported the in vitro results on the target protein. Though all three compounds were poorly stable within an acidic environment, they were only slightly cleared in the in vitro liver model. This is likely the reason why the promising in vitro activity did not translate into in vivo activity on S. haematobium. This limitation could not be overcome by the formulation of lipid nanocapsules as a way to improve the in vivo activity. Further studies should focus on increasing the compound's bioavailability, to reach an active concentration in the microenvironment of the parasite.     

Chiral perturbation theory: Expansions in the mass of the strange quark

In a previous paper, we have shown how to systematically determine the low-energy structure of the Green functions in QCD. The present article extends this framework to expansions in the mass of the strange quark. We construct the generating functional of U(3)×U(3) which allows us to calculate the Green functions up to and including terms of order p⁴ (at fixed radio m_quark/p²) in terms of a few coupling constants which chiral symmetry leaves undetermined. We calculate the first non-leading term in the quark mass expansion of the order parameters , and of the masses and decay constants in the pseudoscalar octet. The three coupling constants which are not fixed by experimental low-energy information are estimated by invoking large-N_c arguments.     

Comment on the 4kF instability of quasi-one-dimensional systems

It will be shown that the 4k_F-instability, as observed in some TCNQ compounds, may be understood as a second-order effect of the electron gas. Moreover, the presented approach suggests a further instability at 6k_F.