The comparative roles of the proton-acceptor properties of amide and carboxyl groups in influencing crystal packing patterns: doubly vs. singly hydrogen-bonded systems in N-acylamino acids and in other amide-acid crystals

Abstract

Doubly vs. singly hydrogen-bonded arrangements in crystalline N-acylated amino acids R-CONH-CHR'-C02H are examined by energy calculations. The O(amide) is a significantly stronger proton acceptor than the O(carboxy1). Thus in one-third of the crystal structures the molecules form doubly hydrogen-bonded systems O-H-.O(amide) and N-H-O(amide), despite the general preference for the maximum number of proton acceptor sites to participate in hydrogen bonds, dictated by molecular packing and conformation. The energy results are consistent with the tendency for the molecules to be interlinked via single hydrogen bonds O-H-O(amide) and N-H-.O(carboxyl), rather than the reverse, and the total absence of the doubly hydrogen-bonded systems 0-H-O(carboxy1) and N-H-(carboxyl).

Crystal structures of N-parabromobenzoyl-α-aminoisobutyric acid and two derivatives

“…The molecules of ;>-BrBz-Aib-OMe (2) form chains of intermolecular hydrogen bonds of the N-H.. .0 = C famide) type, the 0(1).. .N(l) (i-x, y, z-i) distance being 3.003(11) A (Ramakrishnan and Prasad,* 1971;Taylor et al, 1984). These flndings are in accordance with the principle that the maximum number of proton donors and acceptors will participate in the hydrogen bonding scheme, recently put forward in a study of carboxylic amides and acids (Etter, 1982;Berkovitch-Yellin et al, 1983).…”

Linear oligopeptides. 188.Crystallographic characterization of the conformation of the 1-aminocyclopentane-1-carboxylic acid residue in simple derivatives

“…1 -y, -112 + z) separation is 3.055(3) A (76,77). This is the most common packing motif of N-acyl amino acids (82). However, it is worth remembering that the N-H group is also participating in the intramolecular H-bond with the C1 atom (see above).…”

Structures of N-acetyl-α-aminoisobutyric acid, C6H11NO3, and N-trifluoroacetyl-α-aminoisobutyric acid, C6H8F3NO3

“…(4) and 162(6) ° , respectively. This hydrogenbonding scheme, unusual for an N'~-acylated a-amino acid (Berkovitch-Yellin et al, 1983), together with the known inductive effect of the halo-substituents (Nyquist, 1963;Krueger & Smith, 1967;Moussebois, Heremans, Osinski & Rennerts, 1976;Tesch & Schulz, 1981), is fully in keeping with our solid-state IR absorption data: absence of the -OH stretching mode, 3312 cm -I (hydrogen-bonded NH), 1722 cm -1 and 1706 cm -I (hydrogen-bonded carbonyls of the carboxylic acid and trifluoroacetamido groups) (Valle et aL, 1984).…”

“…Rather, the molecules are held together in the most common arrangement of N'~-acylated a-amino acids (Berkovitch-Yellin, Ariel & Leiserowitz, 1983), i.e. by the formation of a network of O-H...O= C(amide) and N-H...O=C(carboxylic acid) intermolecular hydrogen bonds (Fig.…”