CE frontal analysis based on simultaneous UV and contactless conductivity detection: a general setup for studying noncovalent interactions

CE frontal analysis (CE-FA) has been established as a powerful tool to study noncovalent interactions between macromolecules and small molecules such as drug substances or pharmaceutical excipients. However, when using traditional commercial CE instrumentation, a serious drawback is related to the fact that only UV-active compounds can be studied. In recent years, contactless conductivity detection has become an attractive alternative to UV detection in CE due to its high versatility. In this study, we combine contactless conductivity detection and UV detection in a highly versatile setup for profiling noncovalent interactions between low-molecular-weight molecules and macromolecules. In the case of molecules having a chromophore the setup allows determination of binding constants using two independent detectors. The new contactless conductivity detection cell is compatible with commercial CE instrumentation and is therefore easily implemented in any analysis laboratory with CE expertise.     

Effective modulation of DNA duplex stability by reversible transition metal complex formation in the minor groove

Herein we describe the reversible changing of DNA duplex thermal stability by exploiting transition metal complexation phenomena. A terpyridine ligand was conjugated to the N2'-atoms of 2'-amino-2'-deoxyuridine and its locked counterpart 2'-amino-LNA, and these metal-complexing monomers were incorporated into oligodeoxyribonucleotides. Upon addition of varying amounts of transition metal ions, the thermal stability of DNA duplexes containing these terpyridine-functionalized units in different constitutions was affected to different degrees (DeltaTm values = -15.5 to +49.0 degrees C, relative to the unmodified duplex). The most pronounced effects were observed when two complexing monomers were positioned in opposite strands. Addition of 1 equiv of Ni2+ to such a system induced extraordinary duplex stabilization. Molecular modeling studies suggest, as an explanation for this phenomenon, formation of nickel-mediated interstrand linkages in the minor groove. Addition of an excess of metal ions resulted in largely decreased Tm values. Alternating addition of metal ions and EDTA demonstrated reversibility of metal ion-induced changes in hybridization strength, proving that the described approach provides an efficient method for duplex stability modulation.     

Short strong hydrogen bonds in 2-acetyl-1,8-dihydroxy-3,6-dimethylnaphthalene: an outlier to current hydrogen bonding theory?

The environmental influence on the electronic character of two O-H...O hydrogen bonds in a beta-diketone, 2-acetyl-1,8-dihydroxy-3,6-dimethylnaphthalene, is studied by low-temperature synchrotron X-ray diffraction and high-level density functional theory (DFT) calculations. It is revealed that one of the hydrogen bonds is very strong, yet partial localization is found. This result is analyzed by atoms in molecules (AIM) theory and applying the source function. Model compounds, with less steric strain, reveal that the strong hydrogen bond is not merely a result of steric compression.     

Families of vector measures of uniformly bounded variation

We characterize families of vector measures of uniformly bounded variation and semivariation in terms of additivity properties. A classical theorem of Rickart and a simplified proof of Nikodym’s boundedness theorem follow. Received: 3 January 2006; Revised: 31 March 2006 The second named author was supported by Estonian Science Foundation Grant 5704.     

Approximation algorithms for Hamming clustering problems

We study Hamming versions of two classical clustering problems. The Hamming radius p-clustering problem (HRC) for a set S of k binary strings, each of length n, is to find p binary strings of length n that minimize the maximum Hamming distance between a string in S and the closest of the p strings; this minimum value is termed the p-radius of S and is denoted by . The related Hamming diameter p-clustering problem (HDC) is to split S into p groups so that the maximum of the Hamming group diameters is minimized; this latter value is called the p-diameter of S.We provide an integer programming formulation of HRC which yields exact solutions in polynomial time whenever k is constant. We also observe that HDC admits straightforward polynomial-time solutions when k=O(logn) and p=O(1), or when p=2. Next, by reduction from the corresponding geometric p-clustering problems in the plane under the L₁ metric, we show that neither HRC nor HDC can be approximated within any constant factor smaller than two unless P=NP. We also prove that for any >0 it is NP-hard to split S into at most pk^1/7− clusters whose Hamming diameter does not exceed the p-diameter, and that solving HDC exactly is an NP-complete problem already for p=3. Furthermore, we note that by adapting Gonzalez' farthest-point clustering algorithm [T. Gonzalez, Theoret. Comput. Sci. 38 (1985) 293–306], HRC and HDC can be approximated within a factor of two in time O(pkn). Next, we describe a 2^O(p/)k^O(p/)n²-time (1+)-approximation algorithm for HRC. In particular, it runs in polynomial time when p=O(1) and =O(log(k+n)). Finally, we show how to find in

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time a set L of O(plogk) strings of length n such that for each string in S there is at least one string in L within distance (1+), for any constant 0<<1.     

Atomistic details of precipitates in lean Al–Mg–Si alloys with trace additions of Ag and Ge studied by HAADF-STEM and DFT

Abstract

Bonding energies and volume misfits for alloying elements and vacancies in multicomponent Al–Mg–Si alloys have been calculated using density functional theory (DFT). A detailed atomic scale analysis has been done for characteristic precipitate structures, using high-angle annular dark-field scanning transmission electron microscopy. Two new stacking configurations of the important strengthening phase β′′ were discovered in the Ge-added alloy. All three stacking variations were found to be energetically favourable to form from DFT calculations. The second stacking configuration, β₂′′, contains vacated columns in its unit cell, consequently requiring less solute to create the same volume fraction of precipitate needles. DFT suggests a lower formation enthalpy per atom for β₂′′ when Si is exchanged with Ge. In the alloy containing Ag additions, a new Q’/C-like local configuration containing Ag instead of Cu was discovered, also this phase was deemed energetically favourable from DFT.     

Ruthenium-catalysed synthesis of 2- and 3-substituted quinolines from anilines and 1,3-diols

A straightforward synthesis of substituted quinolines is described by cyclocondensation of anilines with 1,3-diols. The reaction proceeds in mesitylene solution with catalytic amounts of RuCl(3)·xH(2)O, PBu(3) and MgBr(2)·OEt(2). The transformation does not require any stoichiometric additives and only produces water and dihydrogen as byproducts. Anilines containing methyl, methoxy and chloro substituents as well as naphthylamines were shown to participate in the heterocyclisation. In the 1,3-diol a substituent was allowed in the 1- or the 2-position giving rise to 2- and 3-substituted quinolines, respectively. The best results were obtained with 2-alkyl substituted 1,3-diols to afford 3-alkylquinolines. The mechanism is believed to involve dehydrogenation of the 1,3-diol to the 3-hydroxyaldehyde which eliminates water to the corresponding α,β-unsaturated aldehyde. The latter then reacts with anilines in a similar fashion as observed in the Doebner-von Miller quinoline synthesis.     

Unlocked nucleic acid--an RNA modification with broad potential

The first unlocked nucleic acid (UNA) monomer was described more than a decade ago, but only recent reports have revealed the true potential applications of this acyclic RNA mimic. UNA monomers enable the modulation of the thermodynamic stability of various nucleic acid structures such as RNA and DNA duplexes, quadruplexes or i-motifs. Moreover, UNA monomers were found to be compatible with RNase H activity, a property which is important for single stranded antisense constructs. Notably, UNA monomers can be applied in the design of superior siRNAs, combining potent gene silencing and dramatically reduced off-target effects.     

Light-induced cytotoxicity of a photochromic spiropyran

In this work we present a novel water soluble spiropyran photoswitch that can be photonically activated inside live cells from a form that has no significant effect on the cellular survival to a form that induces a dramatic toxic response.     

Frequency-domain Fourier-transform terahertz spectroscopy of the single-molecule magnet (NEt4)[Mn2(5-Brsalen)2(MeOH)2Cr(CN)6

We have investigated the novel single-molecule magnet (NEt(4))[Mn(2)(5-Brsalen)(2)(MeOH)(2)Cr(CN)(6)] (1; 5-Brsalen = N,N'-ethylenebis(5-bromosalicylidene)iminato anion) using spectroscopic as well as magnetization and susceptibility measurements. Frequency-domain Fourier-transform terahertz electron paramagnetic resonance (FDFT THz-EPR) based on the generation of THz radiation from a synchrotron in combination with inelastic neutron scattering (INS) allows for the discrimination between intermultiplet and intramultiplet transitions. Together with ac/dc magnetic susceptibility measurements the obtained set of data provides a complete characterization of the lowest energetic magnetic excitations. We find that the new compound 1 exhibits much weaker intermolecular interactions than found in the closely related compound: K[Mn(2)(5-Brsalen)(2)(H(2)O)(2)Cr(CN)(6)] (2). Furthermore, two phonon lines in the vicinity of the magnetic excitations are detected.