Rüdiger Faust

Mapping the melatonin receptor. 6. Melatonin agonists and antagonists derived from 6H-isoindolo[2,1-a]indoles, 5,6-dihydroindolo[2,1-a]isoquinolines, and 6,7-dihydro-5H-benzo[c]azepino[2,1-a]indoles.

6H-Isoindolo[2,1-a]indoles (5, 7, 10, 13), 5,6-dihydroindolo[2, 1-a]isoquinolines (20, 21), and 6,7-dihydro-5H-benzo[c]azepino[2, 1-a]indoles (23, 25, 27, 30) have been prepared as melatonin analogues to investigate the nature of the binding site of the melatonin receptor. The affinity of analogues was determined in a radioligand binding assay using cloned human mt(1) and MT(2) receptor subtypes expressed in NIH 3T3 cells. Agonist and antagonist potency was measured using the pigment aggregation response of a clonal line of Xenopus laevis melanophores. The 2-methoxyisoindolo[2, 1-a]indoles (7a-d) showed much higher binding affinities than the parent isoindoles (5a-e), and whereas 7a-c were agonists in the functional assay, 7d and 5a-e were antagonists. The 2-ethoxyisoindolo[2,1-a]indoles (10a-d) showed reduced binding affinities compared to their methoxy analogues, while the 5-chloro derivative 13 showed a considerable reduction in binding affinity and potency compared to 7a. The 10-methoxy-5,6-dihydroindolo[2, 1-a]isoquinolines (21a-c) had higher binding affinities than the corresponding parent indoloisoquinolines (20a-c) in the human receptor subtypes, and the parent compounds were antagonists whereas the 10-methoxy derivatives were agonists in the functional assay. The N-cyclobutanecarbonyl derivatives of both the parent (20d) and 10-methoxyl (21d) series had similar binding affinities and were both antagonists with similar potencies. The 11-methoxy-6, 7-5H-benzo[c]azepino[2,1-a]indoles (25a-d) had higher binding affinities than the corresponding parent compounds (23a-d) at the MT(2) receptor but similar affinities at the mt(1) site; all of the compounds were antagonists in the functional assay. Changing 11-methoxy for 11-ethoxy decreased the binding affinity slightly, and this was more evident at the MT(2) receptor. All of the derivatives investigated had either the same or a greater affinity for the human MT(2) receptor compared to the mt(1) receptor (range 1:1-1:132). This suggests that the mt(1) and MT(2) receptor pockets differ in their ability to accommodate alkyl groups in the indole nitrogen region of the melatonin molecule. Two compounds (7c and 25c) were tested in functional assays on recombinant mt(1) and MT(2) melatonin receptors. Compound 7c is a potent agonist with some selectivity (44-fold) for the MT(2) receptor, while 25c is an MT(2)-preferring antagonist. Increasing the carbon chain length between N-1 of indole and the 2-phenyl group from n = 1 through n = 3 leads to a fairly regular decrease in the binding affinity, but, remarkably, when n = 3, it converts the methoxy compounds from melatonin agonists to antagonists. The Xenopus melatonin receptor thus cannot accommodate an N-n-alkyl chain attached to a 2-phenyl substituent with n > 2 in the required orientation to induce or stabilize the active receptor conformation.

Fullerene-acetylene hybrids: Towards a novel class of molecular carbon allotropes

Abstract The synthesis and complete characterization of 17 new fullerene-acetylene covalent derivatives is described. Reaction of 3-bromo-1,5-bis(trimethylsilyl)penta-1,4-diyne (5) with C60 gave bis-protected diethynylmethanofullerene 4 in 56% yield. Unsymmetrically bis-protected diethynylmethanofullerene 6 was synthesized in 53% yield from tosylhydrazone 7 and C60. Proto-desilylation of 4 and 6 gave the corresponding free alkynes 3 and 8 in 83% and 69% yield, respectively. Partial deprotection of 4 afforded mono-protected fullerene 9 in 35% yield. Oxidative hetero-coupling reactions of 3 and 8 under Hay conditions with various monosubstituted acetylenes gave the butadiynylmethanofullerenes 10–13 in yields varying from 25–49%. Homo-coupling of 8 produced dumbbell-shaped fullerene 14, the first dimeric fullerene that could be fully characterized. The X-ray crystal structure analysis of 14 revealed little or no electronic interaction between the two fullerene spheres. Addition of lithium trimethylsilylacetylide to C60 gave access to 1-substituted-2-(trimethylsilylethynyl)fullerenes. The acidity of hydrofullerene 16, synthesized in 58% yield, was studied as a function of base and solvent. Reaction of lithiated fullerene 17 with various electrophiles is discussed. Alcohol 25 was prepared in 57%yield by reaction of 17 with formaldehyde. Under strongly basic conditions, 25 eliminates formaldehyde to give 16 in quantitative yield. Oxidation of 25 afforded aldehyde 27 in 53% yield, a rather unstable compound that is easily converted to hydrofullerene 16. Conversion of 25 to the corresponding tosylate could be performed in 40% yield.

ONE-STEP SYNTHESIS OF DIALKYNYL-1,2-DIONES AND THEIR CONVERSION TO FUSED PYRAZINES BEARING ENEDIYNE UNITS

Abstract A convenient procedure for the preparation of symmetrically end-protected dialkynyl-1,2-diones 3 from lithium acetylides and oxalyl chloride in the presence of CuBr and LiBr is described. The condensation of 3 with various aromatic and heteroaromatic 1,2-diamines leads to pyrazine-based α-dialkynylated heterocycles. The enediyne substructure of diethynylquinoxaline can be thermally rearranged in a Bergman cyclization reaction.

FIRST 2,3-DIALKYNYL-1,4-DIAZABUTADIENES BY PD-CATALYZED CROSS-COUPLING OF BIS(IMIDOYL CHLORIDES) AND ALKYNYLSTANNANES

Abstract A general procedure for a palladium-mediated organyl group transfer from organostannanes to bis(imidoyl chlorides) has been developed on the basis of the Pd 2 (dba) 3 ·CHCl 3 /AsPh 3 catalyst system. This protocol allows the synthesis of 2,3-dialkynyl-1,4-diazabutadienes and of trialkynyl-1,3,5-triazines from cyanuric chloride.

Light-harvesting with panchromatically absorbing BODIPY–porphyrazine conjugates to power electron transfer in supramolecular donor–acceptor ensembles

Prerequisites for the design of efficient organic solar light converting systems are intense absorptions across the visible region, the ability to funnel excited state energy by intramolecular energy transfer, and the option to partake in photoinduced electron transfer processes. We have established a versatile synthesis platform for functionalized porphyrazines and present the synthesis of a light harvesting dibenzoquinoxalinoporphyrazine that is peripherally substituted with eight alkynyl-linked BODIPY chromophores. Photophysical investigation by means of time-resolved fluorescence and femtosecond transient absorption spectroscopy revealed efficient intramolecular energy transfer from the photoexcited BODIPY to the porphyrazine core. Coordination of a pyridyl-functionalized phenothiazine (PTZ) to the central metal ion of the porphyrazine generates a complex capable of an efficient electron transfer from the PTZ to the photoexcited porphyrazine core. The porphyrazine˙−/PTZ˙+ fingerprints in the visible and in the near-infrared regions as well as the electron transfer dynamics were determined using spectroelectrochemistry and femtosecond transient absorption spectroscopy. The findings form the basis for the development of supramolecular multichromophore ensembles as materials in solar light converting systems.

En route towards panchromatic light harvesting: photophysical and electrochemical properties of Bodipy–porphyrazine conjugates

The concept of panchromatic light harvesting, that is, broad absorption cross sections throughout most of the visible range and excited state funnelling, has been realized in a novel set of porphyrazines. On one hand, zinc, copper, or magnesium ions were complexed by porphyrazines to tune their ground and excited state features. On the other hand, up to eight Bodipys were covalently attached to the periphery of the porphyrazines to enhance the ground state absorption. The corresponding star-shaped conjugates were probed by advanced photophysical measurements, that is, time-resolved fluorescence and femtosecond transient absorption spectroscopy. From the latter we derive spectroscopic and kinetic evidence in support of a fast and unidirectional energy transfer from the photoexcited Bodipy at the periphery to the porphyrazine at the core. In addition, the impact of the different metal centers is demonstrated.

Mono- and di-nuclear platinum σ-acetylide complexes of tetraethynylethene

Syntheses and X-ray structural characterizations of two types of platinum σ-acetylide complexes in which the metals are bound to tetraethynylethene skeletons are reported; these complexes are closely related to the basic constituents of a metal-linked carbon network and are prepared to explore the feasibility of thermodynamically controlled metal-acetylenic self assembly.

Persistent carbenes containing acetylenes:4,5-dialkynylimidazol-2-ylidene

A nucleophilic imidazole carbene featuring acetylene substituents in the 4- and 5-positions is prepared in three steps from dialkynyl diimines and is characterised by low temperature NMR spectroscopy and trapping reactions with MeI, CS2 and HgCl2.

2,3-Dialkynyl-1,4-diazabuta-1,3-dienes as Novel π-Systems: Synthesis, Structure, and Electronic Properties

The introduction of alkynyl groups into the 2,3-positions of the 1,4-diazabuta-1,3-diene (DAD) backbone succeeds along two complementary synthetic routes either by condensing triisopropylsilyl-terminated dialkynyl-1,2-diones with primary aromatic amines or by a palladium-mediated alkynylation of bis(imidoyl chlorides). X-ray crystallographic analyses of two dialkynyl DAD derivatives reveals their planar (E-s-trans-E) conformations in the solid state. However, the central CC bond of both DAD backbones investigated has a length of 1.491(2) A, and is therefore too long to indicate efficient delocalization across the DAD core. The UV/Vis spectra of dialkynyl DADs demonstrate that their absorptions in comparison to those of non-alkynyl DADs are bathochromically shifted by more than 40 nm, thereby demonstrating the suitability of the title compounds for developing NIR chromophores. The electron absorption properties of differentially N,N′-disubstituted dialkynyl DADs gave no indication for a push-pull effect across the DAD skeleton and suggest the ynimine moiety as the active chromophore of dialkynyl DADs. The electrochemical properties of the title compounds were determined by cyclo- and steady state voltammetry and show that introducing alkynyl groups leads to more easily reducible DAD systems. Again, the perception of dialkynyl DADs as covalently linked, but electronically decoupled ynimine units is corroborated by the redox potential of a differentially N,N′-disubstituted dialkynyl DAD. Similar conclusions were drawn from semiempirical MO (PM3) calculations of dialkynyl DADs.

Semibuckminsterfullerene: MNDO study of a hemispherical triindenotriphenylene

Semiempirical geometry optimization of triindenotriphenylene predicts a rigid cup-shaped structure with strain-induced bond alternation in the central benzenoid ring; model studies of the corresponding Li complex suggest that metal coordination occurs preferentially from the convex side of the bowl.