Evaluation of the Binding Ability of a Novel Dioxatetraazamacrocyclic Receptor that Contains Two Phenanthroline Units: Selective Uptake of Carboxylate Anions Carla Cruz, ² Rita Delgado, ‡,§ Michael G. B. Drew, | and Vı ´tor Fe ´lix* ,² Departamento Quı ´mica, CICECO, UniVersidade de AVeiro, 3810-193 AVeiro, Portugal, Instituto de Tecnologia Quı ´mica e Biolo ´ gica, UNL, Apartado 127, 2781-901 Oeiras, Portugal, Instituto Superior Te ´ cnico, AV. RoVisco Pais, 1049-001 Lisboa, Portugal, and School of Chemistry, UniVersity of Reading, Whiteknights, Reading RG6 6AD, United Kingdom Vfelix@dq.ua.pt ReceiVed December 25, 2006 The novel dioxatetraaza macrocycle [26]phen 2 N 4 O 2 , which incorporates two phenanthroline units, has been synthesized, and its acid-base behavior has been evaluated by potentiometric and 1 H NMR methods. Six protonation constants were determined, and the protonation sequence was established by NMR. The location of the fifth proton on the phen nitrogen was confirmed by X-ray determinations of the crystal structures of the receptor as bromide and chloride salts. The two compounds have the general molecular formula {(H 5 [26]phen 2 N 4 O 2 )X n (H 2 O) 5-n }X n-1 ‚mH 2 O, where X ) Cl, n ) 3, and m ) 6 or X ) Br, n ) 4, and m ) 5.5. In the solid state, the (H 5 [26]phen 2 N 4 O 2 ) 5+ cation adopts a “horseshoe” topology with sufficient room to encapsulate three or four halogen anions through the several N-H‚‚‚X hydrogen- bonding interactions. Two supermolecules {(H 5 [26]phen 2 N 4 O 2 )X n (H 2 O) 5-n } (5-n)+ form an interpenetrating dimeric species, which was also found by ESI mass spectrum. Binding studies of the protonated macrocycle with aliphatic (ox 2- , mal 2- , suc 2- , cit 3- , cta 3- ) and aromatic (bzc - , naphc - , anthc - , pyrc - , ph 2- , iph 2- , tph 2- , btc 3- ) anions were determined in water by potentiometric methods. These studies were complemented by 1 H NMR titrations in D 2 O of the receptor with selected anions. The H i [26]phen 2 N 4 O 2 i+ receptor can selectively uptake highly charged or extended aromatic carboxylate anions, such as btc 3- and pyrc - , in the pH ranges of 4.0-8.5 and <4.0, respectively, from aqueous solution that contain the remaining anions as pollutants or contaminants. To obtain further insight into these structural and experimental findings, molecular dynamics (MD) simulations were carried out in water solution. Introduction Carboxylate substrates participate in many chemical, biologi- cal, and environmental processes. 1 A wide number of these compounds are used in several industrial applications. 1 For instance, trimesic acid (1,3,5-benzenetricarboxylic acid) is applied in the manufacture of plastics, fibers, water-soluble resins, etc.; oxalic acid is used by the antibiotic industry as a purifying agent of oxytetracycline and chloramphenicol deriva- * To whom correspondence should be addressed. Phone: 351 234 370729, fax: 351 234 370084. ² Universidade de Aveiro. ‡ Instituto de Tecnologia Quı ´mica e Biolo ´gica. § Instituto Superior Te ´cnico. | University of Reading. (1) (a) Supramolecular Chemistry of Anions; Bianchi, A.; Bowman- James, K.; Garcı ´a-Espan ˜a, E., Eds.; Wiley-VCH: New York, 1997. (b) Amendola, V.; Bonizzoni, M.; Esteban-Go ´ mez, D.; Fabbrizzi, L.; Licchelli, M.; Sanceno ´n, F.; Taglietti, A. Coord. Chem. ReV. 2006, 250, 1451-1470. 10.1021/jo062653p CCC: $37.00 © 2007 American Chemical Society J. Org. Chem. 2007, 72, 4023-4034 4023 Published on Web 04/21/2007