Carboxylic acid encapsulants

The boronic acid (B), carboxylic acid (C), and primary amide (A) were first used in pairwise competitions with 1 equiv. of each guest (relative to the extended capsule). Separate signals are seen for the N-H resonances of the benzamide and phenyl boronic acid co-encapsulated with corresponding carboxylic acids (Fig. 11). All three combinations and their respective homodimers were observed. The symmetrical homodimers are half as probable as the heterodimers with distributions of 25% and 50%, respectively. The carboxylic acid (C) and amide (A) formed a heterodimer (BC = 53%) but its concentration is 4.8 times that of the underrepresented amide dimer (AA =11%) and 1.5 times that of the carboxyl dimer (CC = 36%). The BC heterodimer matches the best donor with the best acceptor but its concentration is merely what is statistically expected. The real difference is... 

Scheme 5.11 Reaction routes for various saturated and unsaturated carboxylic acids and alcohols using a rhodium catalyst and a lipase. s-g indicates sol-gel encapsulation of the catalyst superscript u and s indicate unsaturated and saturated compounds,...

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. 

Another synthetic polymer that has shown promise in recent clinical trials for the micellar encapsulation of anticancer dmgs is a block copolymer of PEG and poly (aspartic acid) [PEG-Z -P(Asp)]. Doxombicin can be covalently attached to PEG-fi-P(Asp) through the free carboxylic acid groups on aspartic acid, and the block copolymer then forms micelles in solution with the hydrophobic aspartic acid and dmg block forming the core (Yokoyama et al. 1991 Kataoka et al. 1993). As typically occurs, the hydrated PEG chains significantly increased blood circulation... 

An example of the above mentioned cascade complexation of carboxylates by macrocyclic receptors containing metal ionic centers is the inclusion of oxalate by the dien dicobalt complex 9 (Martell, Mitsokaitis) [12]. Similarly, the -cyclodextrin (jS-CD) 10, modified with a zinc cation bound by a triamine side chain, encapsulates anions like 1-adamantylcarboxylate in its cavity, fixing them by combined electrostatic and hydrophobic interactions [13], Zinc s group achieved the enantioselective transport of the potassium salts of N-protected amino acids and dipeptides by making use of the cation affinity of... 

Hydrogels prepared via homogeneous esterification of dextran with unsaturated carboxylic acids are advanced polysaccharide-based products useful for drug delivery systems and protective encapsulants, e.g. of viruses used in gene therapy [173]. Very promising in this regard is the dextran maleic acid monoester [174], which can be obtained by conversion of dextran in DMF/LiCl with the maleic anhydride in the presence of TEA. The DS of the products can be easily controlled with the amount of anhydride applied but... 

To further explore the environment inside such hexameric hosts, Atwood and coworkers performed structural characterization and spectrofluorometric studies of the capsule-bound fluorescent probe molecule pyrene butyric acid (PBA) 52 [71]. Single-crystal X-ray diffraction studies on 52 (50b)6 show not only that encapsulated guests interact with the host walls in the solid state, but also that the n surfaces of the guest molecules are well separated from one another within the capsule. The spectroscopic studies in solution corroborated this finding and revealed an average of 1.5 molecules of 52 per capsule. The assembly remains intact over four weeks in the solution phase, suggesting that the carboxylic acid groups and the polyaromatic nature of 52 do not destabilize the overall supramolecular assembly. 

While this notion may conjure up visions of plastic materials it is important to remember that proteins and nucleic acids are also polymers. Many proteins form globular structures and, indeed, may interlock to encapsulate a large volume of space as exemplified by the coatings of capsid viruses. In a prebiotic world, polypeptides could have formed in aqueous solution through the sequential reaction of amino acids. The individual amino acids hydrogen bond donor and acceptor groups, amines, carbonyls and carboxylic acids, would all have helped to keep the molecules in solution. Once a polypeptide had formed, however, many of these would be unavailable as they became incorporated in the hydrogen bond network that formed the secondary and tertiary structure. This would result in a more hydrophobic surface for the protein capsule which would make an effective cell. 

Fig. 9 H/D isotope effects on the hydrogen bond geometries H/D isotope effects, A5 = 8Hd - SHh. for the encapsulated benzoic acid (BA) derivatives (d12 mesitylene, open circles) and non-encapsulated (CDF3/ CDF2C1 filled circles) dimers of carboxylic acids as a function of the bridging proton chemical shift 8Hh...

We compared combinations of encapsulated carboxylic acids, boronic acids, and carboxamides to determine the strongest interactions - at least in the context of the capsule [55], Direct competition experiments between guests of the same size (the p-ethyl derivatives) were used to eliminate the effects of fit . 

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