2- and 2,7-Substituted para-N-Methylpyridinium Pyrenes: Syntheses,Molecular and Electronic Structures,Photophysical, Electrochemical,and Spectroelectrochemical Properties and Binding to Double-Stranded (ds) DNA

Two N-methylpyridinium compounds and analogous N-protonated salts of 2- and 2,7-substituted 4-pyridyl-pyrene compounds were synthesised and their crystal structures, photophysical properties both in solution and in the solid state, electrochemical and spectroelectrochemical properties were studied. Upon methylation or protonation, the emission maxima are significantly bathochromically shifted compared to the neutral compounds, although the absorption maxima remain almost unchanged. As a result, the cationic compounds show very large apparent Stokes shifts of up to 7200 cm⁻¹. The N-methylpyridinium compounds have a single reduction at ca. −1.5 V vs. Fc/Fc⁺ in MeCN. While the reduction process was reversible for the 2,7-disubstituted compound, it was irreversible for the mono-substituted one. Experimental findings are complemented by DFT and TD-DFT calculations. Furthermore, the N-methylpyridinium compounds show strong interactions with calf thymus (ct)-DNA, presumably by intercalation, which paves the way for further applications of these multi-functional compounds as potential DNA-bioactive agents.     

Directed Design of a AuI Complex with a Reduced Mesoionic Carbene Radical Ligand: Insights from 1,2,3-Triazolylidene Selenium Adducts and Extensive Electrochemical Investigations

Carbene-based radicals are important for both fundamental and applied chemical research. Herein, extensive electrochemical investigations of nine different 1,2,3-triazolylidene selenium adducts are reported. It is found that the half-wave potentials of the first reduction of the selones correlate with their calculated LUMO levels and the LUMO levels of the corresponding triazolylidene-based mesoionic carbenes (MICs). Furthermore, unexpected quasi-reversibility of the reduction of two triazoline selones, exhibiting comparable reduction potentials, was discovered. Through UV/Vis/NIR and EPR spectroelectrochemical investigations supported by DFT calculations, the radical anion was unambiguously assigned to be triazoline centered. This electrochemical behavior was transferred to a triazolylidene-type MIC-gold phenyl complex resulting in a MIC-radical coordinated Au^I species. Apart from UV-Vis-NIR and EPR spectroelectrochemical investigations of the reduction, the reduced gold-coordinated MIC radical complex was also formed in situ in the bulk through chemical reduction. This is the first report of a monodentate triazolylidene-based MIC ligand that can be reduced to its anion radical in a metal complex. The results presented here provide design principles for stabilizing radicals based on MICs.     

Copolymers of 7-oxabicyclo[2.2.1] heptane with 1,3-dioxane and promesogenic telechelic oligomers thereof

Copolymers of 7-oxabicyclo[2.2.1] heptane (B) (and of its 2-methyl derivatives) with 1,3-dioxane (D) were obtained by cationic copolymerization initiated with benzoylium hexafluoroantimonate. Structure of copolymers was determined by ₁H- and ₁₃C-NMR. The proportion of the acetal bonds in copolymers was additionally confirmed in studies of the products of hydrolysis (only the acetal bonds hydrolyze). D is unable to homopolymerize for the thermodynamic reasons and therefore mostly pseudoperiodic copolymers (-DB_x-)_y are formed. Nevertheless, the reshuffling reactions are responsible for the appearance of “wrong” units. These are: the separate oxymethylene and oxy-1,3-propylene units (P, subunits of D) located between two B units. Only the acetal bonds are cleaved in the acidic hydrolysis with dilute HCl. This gives the promesogenic telechelic oligomers of mostly HO-P-B_x-OH structure. This article is the first to describe successful cationic copolymerization of a cyclic acetal with a cyclic ether. Moreover, the inability of D to homopolymerize gives the thermodynamic basis of the pseudoperiodic copolymer formation. © 1997 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 35 : 1733–1742, 1997     

T3P-Promoted Synthesis of a Series of 2-Aryl-3-phenyl-2,3-dihydro-4H-pyrido[3,2-e][1,3]thiazin-4-ones and Their Activity against the Kinetoplastid Parasite Trypanosoma brucei

A series of fourteen 2-aryl-3-phenyl-2,3-dihydro-4H-pyrido[3,2-e][1,3]thiazin-4-ones was prepared at room temperature by T3P-mediated cyclization of N-phenyl-C-aryl imines with thionicotinic acid, two difficult substrates. The reactions were operationally simple, did not require specialized equipment or anhydrous solvents, could be performed as either two or three component reactions, and gave moderate–good yields as high as 63%. This provides ready access to N-phenyl compounds in this family, which have been generally difficult to prepare. As part of the study, the first crystal structure of neutral thionicotinic acid is also reported, and showed the molecule to be in the form of the thione tautomer. Additionally, the synthesized compounds were tested against T. brucei, the causative agent of Human African Sleeping Sickness. Screening at 50 µM concentration showed that five of the compounds strongly inhibited growth and killed parasites.     

Luminescent Complexes of Europium (III) with 2-(Phenylethynyl)-1,10-phenanthroline: The Role of the Counterions

New antenna ligand, 2-(phenylethynyl)-1,10-phenanthroline (PEP), and its luminescent Eu (III) complexes, Eu(PEP)₂Cl₃ and Eu(PEP)₂(NO₃)₃, are synthesized and characterized. The synthetic procedure applied is based on reacting of europium salts with ligand in hot acetonitrile solutions in molar ratio 1 to 2. The structure of the complexes is refined by X-ray diffraction based on the single crystals obtained. The compounds [Eu(PEP)₂Cl₃]·2CH₃CN and [Eu(PEP)₂(NO₃)₃]∙2CH₃CN crystalize in monoclinic space group P2_1/n and P2_1/c, respectively, with two acetonitrile solvent molecules. Intra- and inter-ligand π-π stacking interactions are present in solid stat and are realized between the phenanthroline moieties, as well as between the substituents and the phenanthroline units. The optical properties of the complexes are investigated in solid state, acetonitrile and dichloromethane solution. Both compounds exhibit bright red luminescence caused by the organic ligand acting as antenna for sensitization of Eu (III) emission. The newly designed complexes differ in counter ions in the inner coordination sphere, which allows exploring their influence on the stability, molecular and supramolecular structure, fluorescent properties and symmetry of the Eu (III) ion. In addition, molecular simulations are performed in order to explain the observed experimental behavior of the complexes. The discovered structure-properties relationships give insight on the role of the counter ions in the molecular design of new Eu (III) based luminescent materials.     

Nanopatterns of molecular spoked wheels as giant homologues of benzene tricarboxylic acids

Molecular spoked wheels with D_3h and C_s symmetry are synthesized by Vollhardt trimerization of C_2v-symmetric dumbbell structures with central acetylene units and subsequent intramolecular ring closure. Scanning tunneling microscopy of the D_3h-symmetric species at the solid/liquid interface on graphite reveals triporous chiral honeycomb nanopatterns in which the alkoxy side chains dominate the packing over the carboxylic acid groups, which remain unpaired. In contrast, C_s-symmetric isomers partially allow for pairing of the carboxylic acids, which therefore act as a probe for the reduced alkoxy chain nanopattern stabilization. This observation also reflects the adsorbate substrate symmetry mismatch, which leads to an increase of nanopattern complexity and unexpected templating of alkoxy side chains along the graphite armchair directions. State-of-the-art GFN-FF calculations confirm the overall structure of this packing and attribute the unusual side-chain orientation to a steric constraint in a confined environment. These calculations go far beyond conventional simple space-filling models and are therefore particularly suitable for this special case of molecular packing.

Scanning tunneling microscopy investigations of phenylene-based molecular spoked wheels with D_3h and C_s symmetries on graphite show the competitive or complementary effects of carboxylic acid groups and alkoxy chains on the nanopattern formation.     

Wet-Chemically Prepared Porphyrin Layers on Rutile TiO2(110)

Porphyrins are large organic molecules that are interesting for different applications, such as photovoltaic cells, gas sensors, or in catalysis. For many of these applications, the interactions between adsorbed molecules and surfaces play a crucial role. Studies of porphyrins on surfaces typically fall into one of two groups: (1) evaporation onto well-defined single-crystal surfaces under well-controlled ultrahigh vacuum conditions or (2) more application-oriented wet chemical deposition onto less well-defined high surface area surfaces under ambient conditions. In this study, we will investigate the wet chemical deposition of 5-(monocarboxyphenyl)-10,15,20-triphenylporphyrin (MCTPP) on well-defined rutile TiO₂(110) single crystals under ambient conditions. Prior to deposition, the TiO₂(110) crystals were also cleaned wet-chemically under ambient conditions, meaning none of the preparation steps were done in ultrahigh vacuum. However, after each preparation step, the surfaces were characterized in ultrahigh vacuum with X-ray photoelectron spectroscopy (XPS) and the result was compared with porphyrin layers prepared in ultrahigh vacuum (UHV) by evaporation. The differences of both preparations when exposed to zinc ion solutions will also be discussed.     

When UDG and hAPE1 Meet Cyclopurines. How (5′R) and (5′S) 5′,8-Cyclo-2′-deoxyadenosine and 5′,8-Cyclo-2′-deoxyguanosine Affect UDG and hAPE1 Activity?

Ionizing radiation is a factor that seriously damages cellular mechanisms/macromolecules, e.g., by inducing damage in the human genome, such as 5′,8-cyclo-2′-deoxypurines (cdPus). CdPus may become a component of clustered DNA lesions (CDL), which are notably unfavorable for the base excision repair system (BER). In this study, the influence of 5′S and 5′R diastereomers of 5′,8-cyclo-2′-deoxyadenosine (cdA) and 5′,8-cyclo-2′-deoxyguanosine (cdG) on the uracil-DNA glycosylase (UDG) and human AP site endonuclease 1 (hAPE1) activity has been taken under consideration. Synthetic oligonucleotides containing 2′-deoxyuridine (dU) and cdPu were used as a model of single-stranded CDL. The activity of the UDG and hAPE1 enzymes decreased in the presence of RcdG compared to ScdG. Contrary to the above, ScdA reduced enzyme activity more than RcdA. The presented results show the influence of cdPus lesions located within CDL on the activity of the initial stages of BER dependently on their position toward dU. Numerous studies have shown the biological importance of cdPus (e.g., as a risk of carcinogenesis). Due to that, it is important to understand how to recognize and eliminate this type of DNA damage from the genome.     

OptDesign: extending optimizable k-dissimilarity selection to combinatorial library design

Optimizable k-dissimilarity (OptiSim) selection entails drawing a series of subsamples of size k from a population and choosing the "best" candidate from each such subsample for inclusion in the selection set. By varying the size of the subsample, one can control the balance between representativeness and diversity in the selection set obtained. In the original formulation, a uniform random sampling from among valid candidates was used to draw the subsamples from a single target population. Here we describe in detail two key modifications that serve to extend the OptiSim methodology to vector selection for interdependent variables, specifically as applied to the design of combinatorial sublibraries. The first modification involves pivoting between variables: subsamples are drawn from each reagent pool in turn, with the viability of each candidate being evaluated in isolation as well as in terms of the products it will produce from complementary reagents already selected. The filters applied may be static or dynamic in nature, with molecular weight and hydrophobicity being examples of the former and structural diversity with respect to reagents already selected being an example of the latter. The second key modification is adding the ability to bias the selection of candidate reagents for inclusion in the subsamples. Taken together, these modifications support the efficient generation of multiblock and other sparse matrix designs that are both representative and diverse, and for which "backfilling" of designs edited to remove undesirable reagents or products is straightforward. The method is intrinsically fast and efficient, since enumeration of the full combinatorial is not required- only those candidates actually considered for inclusion need be evaluated. Moreover, because the subsample selection step is separate from the diversity-based selection of the "best" candidate, incorporating such bias in favor of a competing criterion such as low price provides a "natural," nonparametric mechanism for generating designs that are likely to be "good" in a double-objective, Pareto sense.     

Solid state separated-local-field NMR spectroscopy on half-integer quadrupolar nuclei: principles and applications to borane analysis

New multidimensional NMR methods correlating the quadrupolar and heteronuclear dipolar interactions affecting a half-integer quadrupolar spin in the solid state are introduced and exemplified. The methods extend separated-local-field magic-angle spinning (SLF MAS) NMR techniques that have been used successfully in spin-(1)/(2) spectroscopy to the study of S >/= (3)/(2) nuclei. In our implementation, these techniques avoid homonuclear proton decoupling requirements by relying on moderately fast MAS rates (6-15 kHz) and use rotor-synchronized constant-time pulse sequences to achieve nearly arbitrary amplifications of the apparent dipolar coupling strengths. The result is a suite of simple 2D NMR experiments, whose line shapes carry valuable information about the structure and dynamics of solids containing quadrupolar and proton nuclei. The potential of these sequences was exploited to gather new insight into the structure and dynamics of a variety of boron-containing samples. These experimental SLF schemes were also extended to 3D NMR experiments that incorporate multiple-quantum MAS, thus enabling the resolution needed to study multiple chemical sites in a solid and providing a useful tool for the assignment of inequivalent sites.