Characterizing Active Pharmaceutical Ingredient Binding to Human Serum Albumin by Spin-Labeling and EPR Spectroscopy.

Drug binding to human serum albumin (HSA) has been characterized by a spin-labeling and continuous-wave (CW) EPR spectroscopic approach. Specifically, the contribution of functional groups (FGs) in a compound on its albumin-binding capabilities is quantitatively described. Molecules from different drug classes are labeled with EPR-active nitroxide radicals (spin-labeled pharmaceuticals (SLPs)) and in a screening approach CW-EPR spectroscopy is used to investigate HSA binding under physiological conditions and at varying ratios of SLP to protein. Spectral simulations of the CW-EPR spectra allow extraction of association constants (KA ) and the maximum number (n) of binding sites per protein. By comparison of data from 23 SLPs, the mechanisms of drug-protein association and the impact of chemical modifications at individual positions on drug uptake can be rationalized. Furthermore, new drug modifications with predictable protein binding tendency may be envisaged.

Octafunctionalized biphenylenes: molecular precursors for isomeric graphene nanostructures.

A straightforward method for the octafunctionalization of biphenylene based on the [2+2]-cycloaddition of an aryne intermediate has been developed. This enabled a "North-South" extension of biphenylene towards isomeric graphene nanoribbons composed of four-, six-, and eight-membered rings. This procedure furthermore allowed an "East-West" expansion to [n]phenylenes with different lengths. For the fabrication of isomeric nanongraphenes, octaarylbiphenylenes decorated with phenyl, pyrenyl, and thieno substituents were prepared. The subsequent oxidative cyclodehydrogenation provided an expanded helicene as a model compound.

Tetramethoxypyrene-based biradical donors with tunable physical and magnetic properties.

Synthesis of 2,7-disubstituted tetramethoxypyrene-based neutral biradical donors is reported. The biradicals were characterized by EPR, UV-vis, CV, SQUID, and single-crystal X-ray diffraction, and their optical, electrochemical, and structural properties were compared and discussed. The experimental results are well supported by DFT calculations. Systematic tuning of magnetic exchange interactions was achieved by varying the radical moieties.

Electron donors and acceptors based on 2,7-functionalized pyrene-4,5,9,10-tetraone.

An efficient synthesis of 2,7-dibromo- and diiodo-pyrene(4,5,8,19)-tetraones led to strong donors and acceptors based on pyrene. They are versatile building blocks for conjugated materials and can be further applied in molecular electronics.

Tuning the HOMO-LUMO gap of pyrene effectively via donor-acceptor substitution: positions 4,5 versus 9,10.

Donor and acceptor substituents were introduced at pyrene's K-regions in order to engineer its optoelectronic properties. A study of the influence of the substitution pattern on the frontier orbitals as well as on the molecular packing is provided. A comparison with the pure donor and acceptor substituted pyrene derivatives highlights the strong impact of the presented donor-acceptor substitution.

π-Conjugated heterotriangulene macrocycles by solution and surface-supported synthesis toward honeycomb networks.

A comparative analysis between a solution and a surface-mediated synthesis of heterotriangulene macrocycles is reported. The results show a preferential formation of the π-conjugated macrocycles on surface due to two-dimensional confinement. The macrocycle prepared on a several hundred milligram scale by solution chemistry was characterized by single-crystal X-ray analysis and was furthermore extended toward next generation honeycomb species. Investigation of the photophysical and electronic properties together with the good thermal stability revealed the potential of MC6 as hole-transport material for organic electronics.

Toward the peri-pentacene framework.

Based on modern pyrene chemistry, a new route toward the synthesis of the peri-pentacene framework was developed. Firstly, the tetraketo form as stable precursor was targeted, because the fully aromatic peri-pentacene is predicted to suffer from high instability and reactivity. Therefore, a recently developed 4,5,9,10-tetrafunctionalization of pyrene was utilized to build up a planar and a dragonfly-shaped derivative in five steps, which only differ in the two outer bonds between the peripheral benzene rings. The planar tetraketone could only be dissolved in strong acids upon protonation, which limited the use of analytical methods. In contrast, the dragonfly-shaped form showed excellent organosolubility. In-depth investigation by NMR spectroscopy revealed co-existence of atropo-isomers in solution. The optical and electronic properties were analyzed by UV/Vis spectroscopy and cyclic voltammetry. To approach aromatic conjugation, stepwise reduction in solution by using tetrabutylammonium borohydride was carried out. Reduced species were studied by ESR and UV/Vis spectroscopy, as well as by MALDI-TOF MS, confirming the formation of the radical anion.

Tetraaryltetraanthra[2,3]porphyrins: synthesis, structure, and optical properties.

A synthetic route to symmetrical tetraaryltetraanthra[2,3]porphyrins (Ar(4)TAPs) was developed. Ar(4)TAPs bearing various substituents in meso-phenyls and anthracene residues were prepared from the corresponding pyrrolic precursors. The synthesized porphyrins possess high solubility and exhibit remarkably strong absorption bands in the near-infrared region (790-950 nm). The scope of the method, selection of the peripheral substituents, choice of the metal, and their influence on the optical properties are discussed together with the first X-ray crystallographic data for anthraporphyrin.

Three-dimensionally arranged cyclic p-hexaphenylbenzene: toward a bottom-up synthesis of size-defined carbon nanotubes.

Go to three dimensions: as a step toward a bottom-up synthesis of size-defined carbon nanotubes (CNTs), [3]cyclo-4',4''''-hexaphenylbenzenes ([3]CHPBs) were synthesized and investigated. Theoretical and experimental results revealed that [3]CHPBs possess highly twisted [9]cyclo-p-phenylene cores. [3]cyclo-2,11-(Hexa-peri-hexabenzocoronene) ([3]CHBC) was also examined for CNT synthesis.

Hexathienocoronenes: synthesis and self-organization.

Here we report hexathienocoronenes (HTCs), fully thiophene-annelated coronenes in which six double bonds in the periphery are thieno-fused. The derivatives tetrasubstituted with hexyl and dodecyl chains show a phase formation that strongly depends on the chain length. HTCs are remarkably stronger donors than the known thiophene-annelated coronenes but do not readily assemble into well-ordered films when deposited from the vapor phase. Thus, thin-film transistors fabricated by vacuum deposition have only modest field-effect mobilities of 0.002 cm(2) V(-1) s(-1).

Making benzotrithiophene a stronger electron donor.

A new member of the benzotrithiophene family, benzo[2,1-b:-3,4-b':5,6-c″]trithiophene (3a), and its alkyl substituted derivatives (3b-e) were synthesized and characterized. Their photophyscial, electrochemical, crystallographic, and self-assembly properties were described. Thin film structures varied widely with the exact nature of the alkyl substitution pattern, with decreasing self-assembly propensity with increasing alkyl chain length. The high HOMO levels and the coplanarity of these molecules show their potential as organic semiconductors and as donor components in donor-acceptor copolymers.

Saddle shaped hexaaryl[a,c,fg,j,l,op]tetracenes from 4,5,9,10-tetrafunctionalized pyrenes.

A new K-region functionalized pyrene is presented which was used as a building block for the straightforward synthesis of hexaaryl[a,c,fg,j,l,op]tetracene via fourfold Stille coupling and subsequent cyclodehydrogenation. Electronic properties and crystal structures are provided and reveal a saddle conformation for the curved hexaarylated tetracenes.

2,5,8,11-Tetraboronic ester perylenediimides: a next generation building block for dye-stuff synthesis.

Via an unprecedentedly reported ruthenium catalyzed reaction, an efficient and straightforward method was developed for the synthesis of 2,5,8,11-tetraboronate perylenediimide derivatives. A possible reaction mechanism is proposed. The synthesis of 2,5,8,11-tetra-iodo and tetra-amino perylenediimides derivatives is also reported.

Asymmetric pyrene derivatives for organic field-effect transistors.

For the synthesis of an ortho-dithienylpyrene, a K-region bromination of pyrene was developed which enabled the first reported, non-statistical asymmetric functionalization of pyrene at the 4, 5, 9 and 10 positions. Crystal structures, optical and electronic properties and FET characteristics have been investigated.

A porphyrin-related macrocycle from carbazole and pyridine building blocks: synthesis and metal coordination.

In this communication, we report the synthesis of a novel porphyrin-related macrocycle. The core modifications result in aromatic building blocks connected exclusively via aryl-aryl bonds. The concept of synthesis permits the formation of a cavity similar to that of a porphyrin combined with the ability to bind metal ions to provide neutral metal complexes.

Alkylsulfides of Ag(I) and Au(I) as metallosurfactants.

Several representative, interfacially active silver(I) nitrate alkylsulfide complexes were synthesized and characterized in detail. The complexes form extended structures in the solid state and in solution. Interestingly, a two-phase approach, in which aqueous silver nitrate is combined with organically dissolved sulfides, leads to the in situ formation of the complexes at the water-organic interface and a strong reduction of the surface tension. Despite their low solubility in water or organic solvent, these complexes are capable of stabilizing eicosane emulsions and dispersions in water. Thus, these silver nitrate alkyl sulfides represent a new class of metallosurfactants in which the metal ion is crucial for the interfacial activity. Gold(I) chloride alkyl sulfides show the same effect to a lesser extent.

Crystal engineering of pharmaceutical Co-crystals: application of methyl paraben as molecular hook.

Applicability of the O-H...N heterosynthon for synthesis of a pharmaceutical co-crystal comprised of a commonly used tablet excipient methyl paraben and quinidine, an anti-malarial constituent of Cinchona tree bark, has been successfully demonstrated. Insights into local conformation and hydrogen-bonding were derived from advanced multinuclear solid-state NMR techniques, where interpretation of the obtained NMR data was supported by DFT quantum-chemical computations. Furthermore, an approach for selective separation of quinidine from its stereoisomer quinine based on the molecular specificity of methyl paraben is presented. It was found that methyl paraben picked its target via hydrogen-bond-mediated molecular recognition, thereby acting as "molecular hook".

Heteroheptacenes with fused thiophene and pyrrole rings.

The preparation of conjugated heteroheptacenes using an electrophilic coupling reaction induced by a super acid is reported. The new molecules containing thiophene and/or pyrrole rings are bisbenzo[b,b']thienodithieno[3,2-b:2',3'-d]pyrrole, bisbenzo[b,b']thienocyclopenta[2,1-b:3,4-b']dithiophene, and bisthieno[3,2-b]thieno[2,3-f:5,4-f']carbazole. Dithieno[3,2-b:2',3'-d]pyrrole, cyclopenta[2,1-b:3,4-b']dithiophene, and carbazole are used as the aromatic cores. This versatility provides access to molecules with systematically controllable physicochemical properties. Single-crystal X-ray analyses demonstrate that the type and position of the alkyl substituents significantly changes the packing properties of the new molecules. The optical and optoelectronic properties of the heteroheptacenes vary considerably depending on the number and position of the sulfur or nitrogen linkages and reveal the improved environmental stability over their hydrocarbon counterparts. The analysis of the experimental results from UV/Vis absorption/photoluminescence (PL) spectroscopy and cyclic voltammetry were combined with DFT quantum-chemical calculations and compared with other model heteroheptacenes. The results suggest that among the acenes with the same number of fused rings, the thiophene ring fusion inside the skeleton stabilizes both HOMO and LUMO levels more effectively than pyrrole and benzene rings. The present study also shows that the new heteroheptacenes are promising candidates for the construction of electronic materials.

Controllable columnar organization of positively charged polycyclic aromatic hydrocarbons by choice of counterions.

A novel columnar organization of ionic complexes based on 9-phenylbenzo[1,2]quinolizino[3,4,5,6-fed]phenanthridinylium (PQP) has been achieved via ionic self-assembly. These complexes represent the first family of polycyclic aromatic hydrocarbons containing a large charged aromatic core with controllable columnar organization in both the crystalline and liquid-crystalline phases. The single-crystal structure of the ionic complex with a benzenesulfonate anion exhibits a staggered dimer arrangement of PQP cations that further establishes columnar superstructures. The use of sulfonate anions with long alkyl tails leads to well-ordered discotic columnar mesophases with an identical staggered packing of the PQP cations.