Neutral substrate recognition

The first tetra-TTF calix[4] pyrrole conjugate 170 has been synthesized by the condensation of acetone and the corresponding monopyrrolo-TTF unit. This calix[4]pyrrole in its 1,3-altemate conformation acted as a host for neutral electron-deficient guests such as 1,3,5-trinitrobenzene, tetrafluoro-p-benzoquinone, tetrachloro-p-benzoquinone and p-benzo-quinone. The addition of chloride ions served to effect release of these guests and thus neutral substrate recognition process could be blocked by the addition of chloride anion (2004JA16296). 

In contrast to coordination of cations or the binding of anions, the recognition of neutral substrates requires binding interactions that are non-electrostatic, or at least non-ionic, in nature. This has made neutral substrate recognition a problem of formidable challenge in... 

Lipooligosaccharide (LOS) bacterial, 25 498 Lipophilic amphiphiles, 24 154-155 Lipophilic interaction dominated substrate recognition, 16 783-786 Lipophilic moieties, 8 706t Lipopolysaccharides (LPS), 4 706 11 47 BPI protein ability to neutralize, 18 257 peptide and protein binding affinity to, 18 256... 

Water molecules or anions close to the active sites in the protease enzymes, mentioned above, may not be considered circumstantial, but may effectively contribute to the removal of the surplus proton from the imidazolium cation before the actual catalytic event. They could serve well to create the initial ion/neutral form of the Aspl02-His57 couple which is important for the initial step of the catalytic process in most discussions 11611 .13i. such a proton removal may be caused by the productive binding of a true substrate (or inhibitor) of the enzyme to the neighboring recognition clefts of the active site. 

In supramolecular chemistry, molecular recognition has evolved over the last 35 years and now much effort is directed towards the complexation of anionic [28], zwitterionic [29], ion-pairs [30] and neutral guests for various purposes, including catalysis [31[. Host molecules can be constructed covalently, or they can themselves also be assembled in a supramolecular fashion. This strategy, called receptor site self-assembly, has been exploited in recent years. Especially, dynamic host formation in the presence of a substrate is highly interesting [32]. 

The spherically shaped cryptophanes are of much interest in particular for their ability to bind derivatives of methane, achieving for instance chiral discrimination of CHFClBr they allow the study of recognition between neutral receptors and substrates, namely the effect of molecular shape and volume complementarity on selectivity [4.39]. The efficient protection of included molecules by the carcerands [4.40] makes possible the generation of highly reactive species such as cyclobutadiene [4.41a] or orthoquinones [4.41b] inside the cavity. Numerous container molecules [A.38] capable of including a variety of guests have been described. A few representative examples of these various types of compounds are shown in structures 59 (cyclophane) 60 (cubic azacyclophane [4.34]), 61a, 61b ([4]- and [6]-calixa-renes), 62 (cavitand), 63 (cryptophane), 64 (carcerand). 

The widely accepted Zn2+-hydroxide mechanism of CA and CPA says the zinc(II)-bound waters that are generated at neutral pH are activated to attack polarised carbonyl substrates. It is noteworthy that carboxamides are substrates for CPA but inhibitors for CA. The visible spectral study of binding of iodoacetamide to colbalt(II)-substituted CA indicates coordination of the amidate N" ion to the metal. In order to answer the question how do zinc(II) ions work differently toward the carboxamides in CA and CPA, the different modes of recognition were mimicked by the use of carboxamide-appended cyclenes (Scheme 20). 

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