Anionic receptor sites

Interaction of Model Opiate Anionic Receptor Sites with Characteristic JV-Substituents of Rigid Opiates PCILO and Empirical Potential Energy Calculations... 

Figure I. Schematic structures of model anionic receptor sites, ammonium methylphosphate (AMP), ammonium methylsulphate (AMS), and the eight compounds studied...

The object of this initial study was to determine whether any net interactions could occur between typical N-substituents and the model anionic receptor site involved in H-bonding with the protonat d amine group, without the steric constraint of attachment of the substituent to the nitrogen. 

N-SUBSTITUENTS WITH MODEL ANIONIC RECEPTOR SITES ... 

Figures 2 and 3 show the optimized geometries obtained from both the PCILO and empirical energy methods for complexes of AMP and AMS with five of the eight compounds studied. The PCILO results give distinct n-ir complexes involving interaction of one oxygen lone pair of electrons with the ir-electron system of the substitutent. In all cases, the empirical energy method gives a totally optimized complex which involves mainly electrostatic and dispersion terms. As can be seen from Figures 2 and 3, the interaction of methylcyclopropane with the model anionic receptor site is the one with the greatest difference...

TABLE III. ANTAGONIST POTENCY AND BINDING AFFINITY OF BENZOMORPHANS WITH VARYING N-SUBSTITUENTS AND THEIR ENERGIES OF INTERACTION WITH MODEL ANIONIC RECEPTOR SITES. ... 

In this study both the PCILO and empirical energy methods were used to characterize intermolecular interactions of typical N-substituents of rigid opiates with model anionic receptor sites. Ammonium methylphosphate (AMP) and ammonium methylsulfate (AMS) were used as model anionic receptor sites. Interaction energies of eight compounds which, as N-substituents. modulate different antagonist/agonist potencies... 

Kobylecki RJ, Carling RW, Lord JAH, Smith CFC, Lane AC (1982) Common anionic receptor site hypothesis its relevance to the antagonist action of naloxone. J Med Chem 25 116-120... 

Working backwards, the positively charged pyrrolidine nitrogen is clearly important since it must bind to the anionic receptor site of the enzyme. 

Because of the resonance of the iminium and carbonium fonns both shown in Table 4, the iminium transfers its positive charge to carbonium, this binding electro-valently the anionic receptor site. The side-chain becomes long enough to bind its phenyl ring. At this point the antagonist may still be displaced from the receptor by any a-sympathomimetic. 

M. W. Hosseini, A. J. Blacker, and J.-M. Lehn, Multiple molecular recognition and catalysis, nucleotide binding and ATP hydrolysis by a receptor molecule bearing an anion binding site, an intercalator group, and a catalytic site, J. Chem. Soc., Chem. Commun. 596(1988). 

Our first generation sapphyrin-sapphyrin dimer is represented by structure 15. In this system, two covalently connected anion binding sites are contained within the same overall recognition framework. It was thus expected that system 15 would act as an effective receptor for dicarboxylate anions under conditions where the corresponding monomeric systems (e.g. 3) would not. Indeed, this proved to be the case (vide infra). 

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]. 

Electrolyte stimulation is chiefly a function of monovalent cations in all animals that have been studied. Consequently, the receptor sites are thought to he anionic The pH relationships of stimulation also indicate that strongly acidic (e.g.. PO, or SOj- ) receptor groups are involved. Calculations... 

Multiple recognition and catalysis in ATP hydrolysis with increased ATP/ADP selectivity has been achieved with a multifunctional anion receptor containing a macrocyclic polyamine as anion binding site, an acridine group as stacking site and a catalytic site for hydrolysis (structure 82) [4.27]. Phosphoryl transfer is accelerated by other types of hydrogen-bonding receptors [5.24a]. 

Calix[4]pyrroles offer an alternative receptor site for the recognition of anions. Miyaji et al. [400] prepared a series of calixpyrrole-anthracene receptors that possess conjugated (73) and unconjugated bond pathways of different lengths (74 and 75). The stability constants (103—105 M-1 determined by NMR titration) for the anion complexes of each member of the series follows the trend... 

---