Inelastic neutron scattering on an Mn10 supertetrahedron: assessment of exchange coupling constants, ferromagnetic spin waves and an analogy to the Hückel method

The synthesis, crystal structure and magnetic characterisation by magnetisation and inelastic neutron scattering (INS) of a mixed-valent Mn(10) supertetrahedral aggregate [Mn(III)(6)Mn(II)(4)(μ(4)-O)(4)(μ(3)-N(3))(3)(μ(3)-Br)(Hmpt)(6)(Br)]Br(0.7)(N(3))(0.3)·2MeOH·3MeCN (1) (H(3)mpt=3-methylpentan-1,3,5-triol) is reported. The magnetic core of the molecule can be described as an octahedron of six S=2 Mn(III) ions with four faces, each capped by a S=5/2 Mn(II) ion such as to form the supertetrahedron. Unlike most related complexes, the molecular symmetry is slightly reduced from approximately T(d) to C(3). The magnetic data reveal a total spin of S=22 in the ground state due to ferromagnetic exchange couplings within the molecule. The combined INS and magnetic data permits the accurate determination of the exchange coupling constants. Two types are found. The couplings between the Mn(III) ions in the inner octahedron are characterised by J(a)=18.4(3) K, whereas the couplings between the apical Mn(II) ions to the neighbouring Mn(III) ions are given by J(b)=7.3(2) K. The significantly larger coupling strength J(a) as compared to J(b), and the near-T(d) symmetry have profound consequences on the energy spectrum, which are discussed and carefully analysed. In particular, the observed INS spectra can consistently be reproduced by a simplified model in which the inner octahedron is replaced by one large spin of length S(0)=12. This model provides intuitive insight into the structure of the magnetic spectrum. Additionally, the magnetic excitations at low temperature are analysed within the frame of ferromagnetic linear spin-wave theory, which permits an analytical calculation of the energy levels. For ferromagnetic clusters, a close analogy to the Hückel method of electronic structure calculation can be drawn, which allows one to grasp the results of the spin-wave theory or the magnetic excitation spectrum, respectively, in a chemical language.     

Neutralizing the Impact of the Virulence Factor LecA from Pseudomonas aeruginosa on Human Cells with New Glycomimetic Inhibitors

Bacterial adhesion, biofilm formation and host cell invasion of the ESKAPE pathogen Pseudomonas aeruginosa require the tetravalent lectins LecA and LecB, which are therefore drug targets to fight these infections. Recently, we have reported highly potent divalent galactosides as specific LecA inhibitors. However, they suffered from very low solubility and an intrinsic chemical instability due to two acylhydrazone motifs, which precluded further biological evaluation. Here, we isosterically substituted the acylhydrazones and systematically varied linker identity and length between the two galactosides necessary for LecA binding. The optimized divalent LecA ligands showed improved stability and were up to 1000-fold more soluble. Importantly, these properties now enabled their biological characterization. The lead compound L2 potently inhibited LecA binding to lung epithelial cells, restored wound closure in a scratch assay and reduced the invasiveness of P. aeruginosa into host cells.     

Excimer formation dynamics in the isolated tetracene dimer

The understanding of excimer formation and its interplay with the singlet-correlated triplet pair state ¹(TT) is of high significance for the development of efficient organic electronics. Here, we study the photoinduced dynamics of the tetracene dimer in the gas phase by time-resolved photoionisation and photoion imaging experiments as well as nonadiabatic dynamics simulations in order to obtain mechanistic insight into the excimer formation dynamics. The experiments are performed using a picosecond laser system for excitation into the S₂ state and reveal a biexponential time dependence. The time constants, obtained as a function of excess energy, lie in the range between ≈10 ps and 100 ps and are assigned to the relaxation of the excimer on the S₁ surface and to its deactivation to the ground state. Simulations of the quantum-classical photodynamics are carried out in the frame of the semi-empirical CISD and TD-lc-DFTB methods. Both theoretical approaches reveal a dominating relaxation pathway that is characterised by the formation of a perfectly stacked excimer. TD-lc-DFTB simulations have also uncovered a second relaxation channel into a less stable dimer conformation in the S₁ state. Both methods have consistently shown that the electronic and geometric relaxation to the excimer state is completed in less than 10 ps. The inclusion of doubly excited states in the CISD dynamics and their diabatisation further allowed to observe a transient population of the ¹(TT) state, which, however, gets depopulated on a timescale of 8 ps, leading finally to the trapping in the excimer minimum.

The understanding of excimer formation and its interplay with the singlet-correlated triplet pair state ¹(TT) is of high significance for the development of efficient organic electronics.     

DNA that is dispersed in the liquid crystalline phases of phospholipids is actively transcribed

We report that a 4.3 kbp linearised T7 DNA plasmid is actively transcribed when it is dispersed in the hexagonal liquid crystalline phase of dioleoylphosphoethanolamine (DOPE).     

Prodrug design for the potent cardiovascular agent Nω-hydroxy-L-arginine (NOHA): synthetic approaches and physicochemical characterization

N(ω)-Hydroxy-L-arginine (NOHA)--the physiological nitric oxide precursor--is the intermediate of NO synthase (NOS) catalysis. Besides the important fact of releasing NO mainly at the NOS-side of action, NOHA also represents a potent inhibitor of arginases, making it an ideal therapeutic tool to treat cardiovascular diseases that are associated with endothelial dysfunction. Here, we describe an approach to impart NOHA drug-like properties, particularly by wrapping up the chemically and metabolically instable N-hydroxyguanidine moiety with different prodrug groups. We present synthetic routes that deliver several more or less highly substituted NOHA derivatives in excellent yields. Versatile prodrug strategies were realized, including novel concepts of bioactivation. Prodrug candidates were primarily investigated regarding their hydrolytic and oxidative stabilities. Within the scope of this work, we essentially present the first prodrug approaches for an interesting pharmacophoric moiety, i.e., N-hydroxyguanidine.     

Synthesis, characterization, and single-molecule metamagnetism of new Co(II) polynuclear complexes of pyridine-2-ylmethanol

The reaction between pyridine-2-ylmethanol (HL), anhydrous CoCl(2) and NaH afforded polynuclear Co(II) complexes [Co(7)(L)(12)]Cl(2) (1), [Co(6)Na(L)(12)]Cl (2) and [Co(4)Cl(2)(L)(6)] (3), depending on the HL:CoCl(2) ratio set in the reaction. The core structures of the centrosymmetric complexes 1 and 2 are of the M@Co(6) type (M = Co or Na, respectively) with a coplanar arrangement of the metals whereas that of centrosymmetric 3 is of an incomplete dicubane type. The experimental conditions allowing interconversions between these polynuclear complexes have been determined, which provides a more rational control of their synthesis. Thus, 1 transforms to 3 when reacted with CoCl(2) in a 1 : 1 ratio, whereas the same reaction performed with a large excess of CoCl(2) gave the tetranuclear pseudo-cubane complex [Co(4)(L)(4)Cl(2)(MeOH)(4)] upon recrystallization. Conversely, 1 was isolated from the reaction of 3 with HL and NaH. The crystal structure of these compounds is reported, along with the magnetic behaviour of 1 and 3. The analysis of the magnetism using the effective spin-1/2 Hamiltonian approach revealed single-molecule metamagnetic behavior in 3.     

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.     

Synthesis and physicochemical characterization of novel 6-aminopyrido[3,4-c][1,9]phenanthrolines as aza-analogs of benzo[c]phenanthridines

Based on the 6-aminobenzo[c]phenanthridines, a compound class showing noteworthy antitumor activity, an efficient one-step synthesis consisting of a base-catalyzed condensation of 2 equiv of 4-methylpyridine-3-carbonitrile and various aldehydes causing twofold ring closure is described. The obtained 6-amino-11,12-dihydropyrido[3,4-c][1,9]phenanthrolines could be aromatized with Pd/C at high temperatures to form 6-aminopyrido[3,4-c][1,9]phenanthrolines. All compounds were systematically characterized regarding both lipophilicity and solubility and a high cytotoxic potential was evaluated in preliminary in vitro studies. Compared to formerly described 6-aminobenzo[c]phenanthridines our newly developed phenanthrolines turned out to possess improved drugability, due to significantly increased water-solubility and decreased lipophilicity.     

Invariants of Multidimensional Time Series Based on Their Iterated-Integral Signature

We introduce a novel class of features for multidimensional time series that are invariant with respect to transformations of the ambient space. The general linear group, the group of rotations and the group of permutations of the axes are considered. The starting point for their construction is Chen’s iterated-integral signature.