The interactions of cyclic peptides containing glycines with cations (Li + , Na + , Be 2+ , Mg 2+ ) and anions (Fand Cl -) have been investigated using ab initio calculations. The cyclic peptides are found to be exciting noVel amphi-ionophores which show strong affinities for both cations and anions. In the presence of a cation, the CdO groups orient toward the center, whereas in the presence of an anion, the N-H groups do so. To our knowledge, we believe that these cyclic peptides are the first amphi-ionophores reported in the literature.Since there are few ionophores for anions, the cyclic peptides would be important anionophores in that they have large anion affinities. Although the individual amide group is rigid, the entire cyclic structures are very flexible, resulting in amphi-ionophores. If glycines are substituted by other residues, it could be utilized to design cyclic peptide ionophores to show different selectivities for cations and anions with varying flexibilities.Host-guest complexation plays a central role in biological processes, such as ion-transfer, enzyme catalysis, and inhibition. 1 In order to elucidate the crucial nature of complex host-(protein)-guest(ions or organic molecules) interactions in biological processes, various experimental 2 and theoretical 3 studies have been done. To design useful ionophores, various important concepts such as host-guest size complementarity, rigidity of host molecule, and ion dipolar moiety orientations in host-guest complexes have been proposed. 4 Considering that real biological hosts are mainly proteins which are polypeptides, it is more desirable to mimic proteins with compounds comprised mainly of peptide bonds. In recent years cyclic polypeptides have been synthesized and used as inhibitors and antagonists. 5 Considering that more than a quarter of all known enzymes require the presence of metal atoms for full catalytic activity, we have performed an ab initio study of the interactions between cyclic peptides and ions, which may have much theoretical and practical importance. To our knowledge, this is the first ab initio study concerning cyclic peptides. In the present study, we investigate a cyclic tetrapeptide (1) and a cyclic hexapeptide (2) which contain only glycines. Although a number of cyclic polypeptides were reported, 5 no cyclic peptide containing only glycines has been reported in the literature. Since this structure exhibits good flexibility, it may show amphi-ionophore characteristics, which will be discussed below.All the structures of compounds 1 and 2 and their ion complexes were fully optimized by Hartree-Fock (HF) calculations. The 6-31+G* (5d) basis set was employed. Calculations based on density functional theory (DFT) employing Becke's three parameter hybrid method using the Lee-Yang-Parr correlation functional (B3LYP) were also performed at the HF/ 6-31+G* optimized geometries for both 1 and 2, and secondorder Möller-Plesset perturbation (MP2) calculations were performed for 1. 6 Basis set superposition error corrections (BSSEC)...

Protonation plays an important catalytic role in amide bond hydrolysis. Although the protonation site of an amide is still debatable, O-protonation is generally preferred to N-protonation in ordinary amides. However, N-protonation can be favored in strained molecular systems. To investigate this strain effect systematically, we studied formamide, strained N-formylazetidine, and highly strained N-formylaziridine using ab initio calculations. The electron correlation effect is found to be important in determining the protonation sites of strained amides, since it contributes to stabilize N-protonation somewhat more than O-protonation. Although O-protonation is highly favored in N-formylazetidine as well as in formamide, N-protonation is favored in N-formylaziridine in both aqueous and gas phases. In case of O-protonation, the geometries become planar even for highly strained amides. The presence of polar solvents contributes to stabilize N-protonation more than O-protonation. The planarity found in O-protonated strained amides and the nonplanarity in N-protonated strained amides would have an important bearing in enzymatic reactions as well as in asymmetric syntheses.

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[16]Starand appears to be a promising ionophore because of its rigid structure with the spherical cavity into which Li+ can fit perfectly. Using ab initio calculations, we investigated if the starand model has strong affinity as well as high selectivity for Li+, compared to 12-crown-4 of almost the same cavity size. Li+ favors the external binding (binding outside of the cavity) for the [16]starand model. The ion−dipolar moiety interactions are found to be the main factors affecting the preference of external binding in the starand model. When a cation is located at the center of the starand model, the out-of-plane bending angle of a cation from the plane of the ketal moiety is more than 90°, resulting in unfavorable energetics. By the same reasoning, the somewhat flexible 12-crown-4 structure, upon complexation with Li+ and Na+, drastically orients itself into a volcano structure with four oxygen atoms on the top so as to have favorable ion−dipolar moiety orientations with the cation located above the volcano. Therefore, in addition to the host−guest size complementarity, the ion-dipolar moiety orientations should be very important in designing novel ionophores.

[reaction: see text] We present an ab initio study of the acid-promoted hydrolysis reaction mechanism of N-formylaziridine in comparison with formamide. Since the rate of amide hydrolysis reactions depends on the formation of the tetrahedral intermediate, we focused our attention mainly on the reactant complex, the tetrahedral intermediate, and the transition state connecting these two stationary points. Geometries were optimized using the density functional theory, and the energetics were refined using ab initio theory including electron correlation. Solvent effects were investigated by using polarizable continuum method calculations. The proton-transfer reaction between the O-protonated and N-protonated amides was investigated. In acidic media, despite that the N-protonated species is more stable than the O-protonated one, it is predicted that both N-protonated and O-protonated pathways compete in the hydrolysis reaction of N-formylaziridine.