Conformational Study of the Structure of Free 18-Crown-6 N. A. Al-Jallal, A. A. Al-Kahtani, and A. A. El-Azhary* Chemistry Department, Faculty of Science, King Saud UniVersity, P.O. Box 2455, Riyadh 11451, Kingdom of Saudi Arabia ReceiVed: January 8, 2005; In Final Form: February 23, 2005 A conformational search was performed for 18-crown-6 using the CONLEX method at the MM3 level. To have a more accurate energy order of the predicted conformations, the predicted conformations were geometry optimized at the HF/STO-3G level and the 198 lowest energy conformations, according to the HF/STO-3G energy order, were geometry optimized at the HF/6-31+G* level. In addition, the 47 nonredundant lowest energy conformations, according to the MP2/6-31+G* energy order at the HF/6-31+G* optimized geometry, hereafter the MP2/6-31+G*//HF/6-31+G* energy order, were geometry optimized at the B3LYP/6-31+G* level. According to the MP2/6-31+G*//B3LYP/6-31+G* energy order, three conformations had energies lower than the experimentally known C i conformation of 18c6. At the MP2/6-31+G*//B3LYP/6-31+G* level, the S 6 lowest energy conformation is more stable by 1.96 kcal/mol than this C i conformation. This was confirmed by results at the MP2/6-31+G* level with an energy difference of 1.84 kcal/mol. Comparison between the structure of the S 6 conformation of 18c6 and the S 4 lowest energy conformation of 12-crown-4, as well as other important conformations of both molecules, is made. It is concluded that the correlation energy is necessary to have an accurate energy order of the predicted conformations. A rationalization of the conformational energy order in terms of the hydrogen bonding and conformational dihedral angles is given. It is also suggested that to have a better energy order of the predicted conformations at the MM3 level, better empirical force fields corresponding to the hydrogen bond interactions are needed. Introduction Although crown ethers were first discovered by Pedersen at du Pont in 1967, 1,2 cyclic polyethers were known long before 3-5 and Pedersen was only the first to indicate their outstanding binding properties. Since their discovery, there has been an immense increase in the interest and research of the chemistry of crown ethers and their applications. For example, a new field in chemistry called molecular design 6 was opened with a large variety of molecules, e.g., cavitands, cryptands, cyclidenes, cryptophanes, etc. Much of the interest in crown ethers is due to their various solubility capability and therefore different binding properties to cations. Crown ethers have numerous applications. They are used in cancer treatment, 7 treatment of nuclear waste, 8 catalysis, 9 control of reaction mechanisms, 10 second-sphere coordination, 11 ion transport, 12 macrocyclic liquid crystals, 13 zeolite synthesis, 14 and ion-selective electrodes. 15 Also, the ability of crown ethers to form complexes with biologically important cations makes them good models as enzyme-binding sites 16 and as ionophores in membrane transport. 17 They are also used in anion activation, 18 cation inhibition, and nucleophilic addition reactions. 19 Crown ethers are composed of two parts, the core part and the side chain attached to the core part. Thus, because of the side chain, crown ethers are called armed crown ethers. The most important core parts are 12-crown-4 (12c4), also known as 1,4,7,10-tetraoxacyclododecane; 15-crown-5 (15c5), known also as 1,4,7,10,13-pentaoxacyclopentadecane; and 18-crown-6 (18c6), known as 1,4,7,10,13,16-hexaoxacycloocatdecane, Fig- ure 1.Because of the widespread applications of crown ethers, there has been a great interest in their conformational analysis. Conformational analysis has been reported for 9-crown-3 (9c3), 20,21 12c4, 22-24 15c5, 25 and 18c6. 26-42 In a recent report, a full conformational search of 12c4 has been performed using the CONFLEX method. 22 The search led to the prediction of 180 conformations at the MM3 level. To get a more accurate energy order of the predicted conformations and to study the dependence of the conformational energy order on the method used, computations were performed at HF/STO-3G level for all conformations and at the HF/4-31G and HF/6-31+G* levels for the 100 lowest energy conformations, according to HF/STO- 3G energy order. In addition, optimized geometries were computed at the B3LYP/6-31+G* and MP2/6-31+G* levels for the 20 lowest energy conformations, according to the MP2/ 6-31+G*//HF/6-31+G* energy order. The function of this study was to be used as a guide in the conformational analysis of the larger 18c6, which has a much larger number of possible * Corresponding author. Tel: (9661) 467 4367; fax: (9661) 467 5992. Figure 1. Structure of some of the crown ethers. 3694 J. Phys. Chem. A 2005, 109, 3694-3703 10.1021/jp050133c CCC: $30.25 © 2005 American Chemical Society Published on Web 04/02/2005