Aromatic spacers

A number of bis(tacn) ligands, composed of pairs of covalently linked tacn macrocycles, can form similar structures, provided the linker group between the sandwiching macrocycles is sufficiently flexible (e.g., (556)).1411-1413 In particular, several Ni11 complexes of poly(tacn) derivatives with a central benzene have been studied, where the Ni is sandwiched between pairs of tacn macrocycles when these are attached to the ortho positions of the aromatic spacer group (e.g., (557)).1412,1413... 

The aromatic spacer group of the model receptors prevent the formation of intramolecular hydrogen bonds between the opposing carboxyls yet these functions are ideally positioned for intermolecular hydrogen bonds of the sort indicated in 32. The acridine derivatives do indeed form stoichiometric complexes with oxalic, malonic (and C-substituted malonic acids) as well as maleic and phthalic acids, Fumaric, succinic or glutaric acids did not form such complexes. Though protonation appears to be a necessary element in the recognition of these diacids, the receptor has more to... 

Following the convergent procedure, dendrimers of type 58,59 and 60 have been prepared from the chiral core triol 54 and achiral Frechet-type [62] ben-zylic branch bromides. In the series of dendrimers with aromatic spacers (60) and without spacers (58), the optical activity [a]D decreased on going from the 1st (not shown in Fig. 21) to the 2nd generation, whereas with aliphatic spacers... 

Aromatic spacers have also been used thus it could be shown for a phenylene-bridged diporphyrinyl system that electron hopping between both subunits can occur (Huber et al, 1990). Here the phenylene bridge is twisted out of conjugation with the two porphyrin rings, and the effect is observed for 1,4-(para) [45a] and the 1,3-(meta) [45b] substitution. 

The development of the next major class of ligands occurred during the 1990s, with Burks DuPhos (42) family of phospholane ligands [222, 223]. (An individual member of the family is named after the substituent R in Me-DuPhos, R=Me.) This structure could be considered an improvement on the DIOP-derived ligands, where the stereogenic centers are now closer to phosphorus. In addition to the aromatic spacer of DuPhos, there is also the related BPE (43) family, where the spacer between the two phosphorus atoms is less rigid. In both series the phosphorus is... 

Fig. 12 Hydroxamic acid and benzamide containing HDAC inhibitors with aromatic spacers. (4 and 5 MethylGene Inc. 3 MethylGene Inc. and TopoTarget UK Ltd.)...

Fig. 14 Saturation of the aromatic spacer deteriorates the potency of a hydroxamic acid-based HDAC inhibitor. (Kansai Univ.)...

Fig. 15 Fine tuning of the (hetero)aromatic spacer of a hydroxamic acid-based HDAC inhibitor—discovery of R306465. (Johnson Johnson Pharmaceutical R D)...

Structures 10. Structures of sulhited spaced glucamines with aromatic spacers... 

The simplest covalently linked systems consist of porphyrin linked to electron acceptor or donor moiety with appropriate redox properties as outlined in Figure 1. Most of these studies have employed free base, zinc and magnesium tetrapyrroles because the first excited singlet state is relatively long-lived (typically 1-10 ns), so that electron transfer can compete with other decay pathways. Additionally, these pigments have relatively high fluorescence quantum yields. These tetrapyrroles are typically linked to electron acceptors such as quinones, perylenes , fullerenes , acetylenic fragments (14, 15) and aromatic spacers and other tetrapyrroles (e.g. boxes and arrays). 

The aromatic spacers are either simply used to replace a part of the peptide stucture, or as templates to induce a specific conformation in the peptide. 

The spacer units in 3.60 are assembled from polyphosphazenes that bear p-bromophc-noxy side groups via a lithiation reaction, and treatment with a diorganochlorophosphine to give 3.62. The chemistry is summarized in reaction sequence (45).107 Polymer 3.62 coordinates to a variety of metallo species,108 including osmium cluster compounds and cobalt carbonyl hydroformylation catalysts. When used as a polymeric hydroformylation catalyst, this latter species proved how stable the polyphosphazene backbone is under the drastic conditions often needed for these types of reactions. The weakest bonds in the molecule proved to be those between the phosphine phosphorus atoms and the aromatic spacer groups. 

The first dendrimers with chiral cores for studies on the influence of the stereo-genic centres of a core unit on the chiroptical properties of the overall molecule were presented by Seebach s group [18]. These workers first synthesised dendrimers based on a chiral tris(hydroxymethyl)methane core unit. To these were attached zeroth- to second-generation Frechet dendrons, either directly or separated from the core by an aliphatic (n-propyl) or an aromatic spacer (p-xylylene) (Fig. 4.62). Remarkably, the dendrimers with aliphatic spacer showed no significant optical activity. This loss of chiral information was attributed to a dilution effecf, resulting from linkage of the achiral dendron to the chiral core unit,... 

Fig. 4.62 Chiral-core dendrimers of various generations (according to Seebach et al.), consisting of a chiral tris(hydroxymethyl) methane core unit and poly (aryl ether) dendrons (GO, Gl, or G2), which are linked to the core either directly (A), via an aliphatic spacer (B), or via an aromatic spacer (C)...

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