Tetralactam macrocycle

MacrocycHc isophthalamides (the tetralactam macrocycles) have been used as a host to build rotaxanes and catenanes by Vogtle and others [15]. Structurally analogous to cyclophanes, their initial usage as a synthetic receptor was for... 

Vogtle has developed this approach further and employed a series of anionic templates to prepare rotaxanes (instead of the neutral template in the above reaction) [65-67]. In this approach a phenolate, thiophenolate or sulfonamide anion is non-covalently bound to the tetralactam macrocycle (46) forming a host-guest complex via hydrogen bonding (see Scheme 21). 

This chapter describes the synthesis, properties, and biomedical applications of cyanine and squaraine dyes encapsulated in CDs, CBs, Leigh-type tetralactam macrocycles, aptamers, and micro- or nano-particles. The optical and photochemical properties of supramolecular guest-host nanostructures that are based on intra-and intermolecular complexes of crown-containing styryl dyes with metal cations, and aggregates of carbocyanine dyes are discussed in a separate review [18]. 

The anlhracene-conVd n ng tetralactam macrocycles 16a and 16b were found to have an extremely high affinity for aniline-based squaraine dyes in chloroform [56]. 

Squaraines 17a-17c were encapsulated in these macrocyles to form the corresponding pseudorotaxanes. Squaraine rotaxanes 14 and 15 with a phenylene tetralactam macrocycle have absorption/emission profiles (Table 3) that closely match those of Cy5, whereas squaraine rotaxanes 16 D 17 with an anthrylene macrocycle have a red-shifted absorption/emission that matches that of the homologous cyanine Cy5.5 (Table 4). These rotaxanes should be useful for fluorescence microscopy imaging applications. 

The impact of self-assembly on the geometry and visible absorption spectrum of a rotaxane formed by squaraine 17a and anthracene-based tetralactam macrocycle 16a was assessed using quantum-chemical DFT, TD-DFT, and QM/MM approaches [57]. 

Squaraines 17b and 17c have terminal acetylene residues, which allowed to convert the squaraine dyes and tetralactam macrocycles into permanently interlocked rotaxane structures using copper-catalyzed and copper-free cycloaddition reactions with bulky stopper groups [58]. 

A variety of hydrophobic and hydrophilic squaraine rotaxane probes and labels such as 21a-21e c Rp and 22a-22e c Rp, containing reactive carboxylic functionalities and hydrophilic sulfo groups, are disclosed in a recent patent application [60]. It was shown that not only aniline-based squaraines 21a-21e but also heterocyclic squaraines 22a-22e can form stable pseudorotaxane complexes. The indo-lenine-based squaraine 22a forms rotaxane 22a C Rp. Importantly, also the sulfonated squaraine 22b could be successfully encapsulated in a Leigh-type, phenylene-based, tetralactam macrocycle to yield the water-soluble rotaxane 22b C Rp. Quatemized, indolenme-based squaraines do not form pseudorotaxanes probably because of sterical hindrance caused by /V-alkyl and 3,3 -dimethyl groups. On the other hand, quatemized benzothiazole (22c) and benzoselenazole (22d) squaraines could be embedded in a Leigh-type macrocycle to yield rotaxanes 22c C Rp and 22d C Rp, respectively. The hydrophilic, mono-reactive rotaxane 22e-NHS C Rp based on asymmetric squaraine, synthesized by a cross-reaction of squaric acid with the two different indolenines, was also obtained. 

Some of the spectral properties of squaraine rotaxanes are given in Table 5. It can be seen that encapsulation of squaraines 22a-22d with heterocyclic end-groups in a tetralactam macrocycle results in a small blue-shift of the absorption and emission maxima while the encapsulation of squaraines 22e and 21a leads to red-shifted rotaxanes [60]. Importantly, encapsulation in a tetralactam macrocycle has a positive effect not only on the photostability (Figs. 9 and 10) of these dyes but also on the quantum yields (<2>F) and fluorescence lifetimes (Tmean)- Embedding of any type squaraines in tetralactam rotaxane system increases [Pg.175]

Encapsulation of squaraine 23a in diastereomeric triptycene-based tetralactam macrocycles 24a and 24b was described in [61], The synthesis of the macrocyclic hosts was done by the reaction of pyridine-2,6-dicarbonyl dichloride and 2,7-diaminotriptycene in dry THF with Et3N. Macrocycles 24a and 24b readily form... 

An overview of the synthesis, structure, photophysical properties, and applications of squaraine rotaxanes as fluorescent imaging probes and chemosensors is provided in a recent review [67]. Although a variety of squaraine dyes form rotaxanes with the molecular cage 25 or with a tetralactam macrocyclic system introduced by Leigh and co-workers [16, 17], there is no evidence in the literature that conventional cyanine dyes can be embedded in these macrocycles. 

Xue M, Chen CF (2008) Triptycene-based tetralactam macrocycles synthesis, structure and complexation with squaraine. Chem Commun 46 6128-6130... 

SCHEME 7 The MACROCYCLIZATION OF PRECURSOR 14 WITH ISOPHTHALIC ACID D1CHLOR1DE UNDER HIGH DILUTION CONDITIONS YIELDS A TETRALACTAM MACROCYCLE 13, THE CATENANE 15, AND A LARGER OCTALACTAM MACROCYCLE 16. 

The most recently discovered template effect is the one that makes use of anions. Vogtle and coworkers [12] have found that a phenolate equipped with one stopper can bind in the cavity of the tetralactam macrocycle by two strong hydrogen bonds. Then this nucleophile complex is reacted with an electrophilic semi-axle to obtain rotaxane in very high yields up to 95%. 

Figure 2. Under high-dilution conditions, die reaction of 1 with isophthaloyl chloride 2 yields tetralactam macrocycle 3, the catenane 4, and octalactam ring 5.

A successful synthesis of a rotaxane of this type is shown in Figure 5. First, one tiityl aniline stopper is reacted with the terephthaloyl chloride to from semiaxle 9. This semiaxle threads into the tetralactam macrocycle 3 and is held by the amide template. Then, the preorganized complex is reacted with the second stopper 11 to yield rotaxane 12. Figure 5 shows three hydrogen bonds to form, which is in accord with AMI calculations on this system [19] and X-Ray crystal structure analysis [22],... 

A molecule with an even more spectacular topology was obtained when extended diamine 13 was reacted with 2,6-pyridine dicarboxylic acid dichloride. This was just a reversal of the order of the reaction steps in Figure 3. As well as the expected tetralactam macrocycle, its larger analogue octalactam wheel and a knot were formed [15], It was very surprising that a knot which bears three crossing points in its molecular... 

Single tetralactam macrocycles on Au(lll) surfaces apparently only build disordered closed films, and clustering at step edges and surface defect sites occurs [145],... 

Fig. 12.4. Left The dipole moment in Debye plotted against the time step. Right Distribution of dipole moments (left-hand-side region smaller dipole moments right-hand-side region larger dipole moments). Both data sets were calculated from a Car-Parrinello molecular dynamics simulation of an isolated tetralactam macrocycle [227].

Scheme 6 Schematic representation of the anion templated synthesis of rotaxanes based on tetralactam macrocycles and a phenolate anions...

Vogtle and coworkers employed anion complexation in new strategies for high-yielding rotaxane syntheses. These workers discovered that phenolate anions, when bound to tetralactam macrocycles (Fig. Ij) such as 24. are capable of reacting with acid chlorides and therefore may be used to form ester rotaxanes. A variety of different rotaxanes were synthesized via this method, including systems with carbonate and acetyl axles. 

Tetralactam macrocycles as a class of hosts with special ability to include anions and organic molecules have been widely applied to construct a variety of interlocked supramolecular assemblies, develop new molecular machines, and... 

Similar to other triptycene-derived macrocyclic arenes, triptycene-derived tetralactam macrocycles also had fixed conformations with large electron-rich cavities, which made them promising candidates as the host for some electron-deficient guests with comparatively large sizes. Squaraines [26] were a family of fluorescent dyes with specific near-IR photophysical properties, which had wide potential applications. However, their instability limited the utilization of them, and thus improving their chemical stability and the photophysical properties were the key to applications of squaraines [27]. Consequently, we [25, 28] found that macrocycles 35a-b could form a new kind of stable pseudorotaxane-type complexes with the squaraine in both solution and solid state. We further studied the chemical stability of squaraine in these complexes, and found that free guest 35b underwent hydrolytic decomposition to turn colorless in polar THF-water solvent in 4 days, but for squaraine 36b (Fig. 18.15) in complexation with 35a-b, its blue colors could be retained for several weeks. This observation revealed that the formation of complexes could efficiently protect the squaraine dyes from polar solvents. 

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