A Simple Helical Macrocyclic Polyazapyridinophane as a Stereoselective Receptor of Biologically Important Dicarboxylates under Physiological Conditions

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• 作者：Almudena Gonz&aacute ; lez-&Aacute ; lvarez ; Ignacio Alfonso ; Pilar Dí ; az ; Enrique Garcí ; a-Españ ; a ; Vicente Gotor-Fern&aacute ; ndez ; Vicente Gotor
• 刊名：Journal of Organic Chemistry
• 出版年：2008
• 出版时间：January 18, 2008
• 年：2008
• 卷：73
• 期：2
• 页码：374 - 382
• 全文大小：280K
• 年卷期：v.73,no.2(January 18, 2008)
• ISSN：1520-6904

文摘

The interaction of a synthetic enantiopure azamacrocyclic receptor (L) with biologically important chiraldicarboxylates (A, 1-7) has been studied by means of potentiometric titrations in 0.15 M NaCl aqueoussolution in a wide pH range. This macrocycle forms strong complexes of the type [H_nLA]^(n-2) (with n =0-5). As a general trend, the binding is much tighter at basic or neutral pH than in acidic medium.Interestingly, nonprotected excitatory amino acids (Asp and Glu) are strongly bound even at acidic pH.Regarding selectivity, the receptor showed stereoselective binding toward those substrates bearing anH-bonding donor at C, being S-selective in most of the cases, except for glutamic acid. Thus, L displayedan excellent enantioselectivity for (S)-malate dianion (K_S/K_R = 11.50 at pH 10.0 and K_S/K_R = 6.86 at pH7.0) and exhibited moderate enantiopreference for (S,S)-tartrate (K_SS/K_RR = 3.01 at pH 10 and K_SS/K_RR= 1.70 at pH 7.0). For this last anion, a very good diastereopreference was also observed (K_SS/K_RS =8.46 at pH 10 and K_SS/K_RS = 4.99 at pH 7.0). On the contrary, L is smoothly R-selective toward (R)-Glu(K_R/K_S = 3.22 at pH 10 and K_R/K_S = 2.05 at pH 7.0) due to its longer and more flexible molecularstructure. The stereoselectivity of the corresponding complexes decreased when decreasing pH values.For the hydroxy derivatives, mass spectrometry also reflected the trends observed by potentiometry andconfirmed the receptor:dicarboxylate 1:1 stoichiometry of the supramolecular complexes. Additionalexperimental techniques were used to study the most stereoselective example. Solution studies by NMRsuggested a good geometrical complementarity between the malate dianion and the receptor, which showeda predominant helical conformation in solution. Besides, self-diffusion rates (PGSE) of the diastereomericcomplexes with malate also agree with binding data. Circular dichroism was also used in this case atdifferent pH values, showing a very good correlation between the helical content of the receptor and thestereoselectivity of the molecular recognition process.