SCIENCE/TECHNOLOGY
Molecular Recognition Found In Simple Alcohol-Amine Complexes (the two lone pairs of electrons on oxygen), whereas primary amine groups have two donors (two hydrogens) and one acceptor (one lone pair). In most crystals of pure alcohols or pure amines, only one hydrogen atom and one lone pair on each hydroxyl or amine group are used to form hydrogen bonds. Ermer and coworkers proposed that Stu Borman, C&EN Washington the complementarity of hydrogen-bond donors and acceptors in alcohols and he concept of "molecular recogni- amines creates a propensity toward tion" typically suggests the type formation of 1:1 alcohol-amine comof interactions that occur between plexes in which all the donors and acan enzyme and its substrate or a hor- ceptors on each functional group parmone and its receptor. But several ticipate in hydrogen bonding. They regroups of researchers recently have alized that in such complexes the shown that molecular recognition is also number of hydrogen bonds would inpossible among compounds as uncom- crease by half, relative to the number in plicated as simple alcohols and amines. pure alcohols or pure amines. More than a year ago, chemistry pro"In a 1:1 alcohol-amine complex," fessor Otto Ermer and graduate student they write, "the number of hydrogenAndreas Eling of the Institute for Organ- bond donors and acceptors is balanced ic Chemistry at the University of Co- and the possibility opens up for comlogne, Germany, conceived a general plete saturation of all potential hydroprinciple for molecular recognition gen-bond valencies. Within fourfold tetamong alcohols and primary amines. rahedral coordination, from every oxyThis was based on the perception that gen and nitrogen atom three hydrogen hydroxyl groups in alcohols and amino bonds would then emanate, as comgroups in amines are complementary in pared with only two in the free alcohol hydrogen bonding, both stoichiometri- and amine, respectively." cally and geometrically [/. Chem. Soc. The additional hydrogen bonds have Perkin Trans. 2,1994,925]. a stabilizing influence and make comAt the same time, the role of chirality plex formation an energetically favorin such interactions was being studied able process. The researchers proposed independently by chemistry professor that molecular recognition was possible Stephen Hanessian and coworkers at the among simple alcohols and amines—a University of Montreal [/. Am. Chem. Soc, 116,4495 (1994)]. And other groups recently have constructed complexes exhibiting alcohol-amine complementarity. "A judicious choice of chiral amine and alcohol partners in which recognition and organization work in concert can provide functionally and topologically unique supramolecular assemblies having discrete shapes and fascinating Alcohols and primary amines have complementary hydrogen-bond dotertiary structures," says Hanessian. nor and acceptor groups (hydrogen The hydroxyl groups found in alcoatoms and lone pairs, respectively). hols have one hydrogen-bond donor (the hydrogen atom) and two acceptors
• Complementarity of hydrogens and lone pairs in alcohols and amines leads to unique class of supramolecular assemblies
phenomenon that had only rarely been recognized before, and then not in such an explicit manner. Hence, they believed it would be possible to construct supramolecular hydrogen-bonded networks of alcohols and amines. Ermer's group demonstrated the principle by preparing several 1:1 corn-
T
Complex between \rans-l,2-diaminocyclohexane and 2,3-butanediol, made by Hanessian and coworkers, adopts triple-stranded helical structure. Diamines are blue and diols are red; only every third strand of the complex is colored to show the trihelical structure of the assembly. DECEMBER 11,1995 C&EN 33
SCIENCE/TECHNOLOGY plexes between linear aromatic diphe- plexation. Later, Hanessian and cowork- tures can be formed with neutral as nols and diamines—for example, an ers Stefano Roelens, Michel Simard, and well as charged alcohol partners. adduct of hydroquinone and p-phe- Arthur Gomtsyan at the University of The helical pattern of the hydrogen nylenediamine. The diphenol-diamine Montreal took alcohol-amine comple- bonds in the diaminocydohexane-butanecomplexes form hydrogen-bonded dia- mentarity and chirality a major step fur- diol complex represents "the first example mond-type crystal lattices in which ther by constructing the first such three- of a self-assembled hydrogen-bonded coil each oxygen and nitrogen atom is co- dimensional assemblies that adopt right- involving amino and hydroxyl groups valently bonded or hydrogen bonded and left-handed helical shapes, depend- exclusively," according to the researchin a tetrahedral configuration. ing on the chirality of the components [/. ers. The crystalline triple-helical complexes are not only esthetically pleasing but James H. Loehlin and a group of un- Am. Chem. Soc., 117, 7630 (1995)]. dergraduate coworkers in the departHanessian sees the self-assembling also potentially useful—for example, to ment of chemistry at Wellesley College, complementarity of amine and alcohol achieve enantiomeric resolution of raceWellesley, Mass., have reported related units as a new tool for designing biolog- mic diamines or diols by physical separation of diastereomeric complexes. complexes. Based on a suggestion from the late Margaret C. Etter, a Professor Fumio Toda of the professor in the department of department of applied chemistry chemistry at the University of at Ehime University, Japan; ProMinnesota, Loehlin's group confessor Ken Hirotsu of the departstructed "host-guest" complexes in ment of chemistry at Osaka City which six guest molecules are University, Japan; and coworkers linked to a central host molecule also are pursuing the compleby hydrogen bonding. The commentarity concept. They have replexes include one between hydroported a water-free 1:1 complex quinone and two anilines [Chem. of hydroquinone (HO-C6H4-OH) Mater., 6,1218 (1994)] and another and hydrazine (H2NNH2) with one between p-phenylenediathe same kind of diamondoid armine and two phenols. chitecture as the Ermer group's hydroquinone-p-phenylenediaResearcher Cedric J. Brown of mine complex [J. Chem. Soc, the dyestuffs division of ICI, Chem. Commun., 1995,1531]. Manchester, England, "did the first work of this type, of which I The complex provides a safe am aware, in his structure of form of anhydrous hydrazine, p-aminophenol published in 1951," which is normally very difficult says Loehlin. However, "only one and dangerous to prepare beor two other structures with this cause it is explosive. Toda, Hirotfeature [saturated alcohol-amine su, and coworkers isolate pure hydrogen bonding] were pubhydrazine from aqueous hydralished prior to Elmer's work," and zine as a stable inclusion complex Brown "didn't directly point out with hydroquinone. the uniqueness of equimolar Toda's group also has shown amine-hydroxyl complementarity" that molecular recognition beas Ermer and coworkers did. tween a chiral alcohol and a race mic amine can be applied to the "To me, the most interesting optical separation of the amine aspect of these structures is that Hydrogen-bond complementarity of alcohols and amines Another potential they provide a unique way to is shown in this model by Ermer and coworkers of aenantiomers. unit application of alcohol-amine comstudy hydrogen bonding, since cell of the crystalline complex formed by hydroquinone one has three different hydrogen and p-phenylenediamine. Oxygen is red, nitrogen isplexes, blue, suggests Toda, involves the cleanup of amine pollution by bonds from each atom," he says. carbon is lavender, and hydrogen is white. trapping volatile amines in incluLoehlin's group currently is investigating a number of aliphatic and ar- ically relevant supramolecular structures sion complexes with alcohol hosts. Ermer points out that complex formaomatic amine-alcohol complexes to ob- based on molecular recognition. "Any tain information about molecular effects time chirality is involved in supramo- tion with aromatic amines also could lecular assemblies, particularly with he- conceivably be used to concentrate on hydrogen bonding. Chiral separations of diols by complex lical motifs, there is potential for refine ethanol from the dilute aqueous soluformation with diamines had been ob- ment in molecular recognition and com- tions in which it is produced by fermentation. The concept of alcohol-amine served in the early 1990s by scientists ing closer to life processes," he says. Hanessian and coworkers have complementarity, he says, represents "a Masatoshi Kawashima and Akihisa Hirayama at Kankyo Kagaku Center formed novel triple-helical complexes body of new, significant, and applicaCo., Yokohama, Japan [Chem. Lett, 1991, between frans-l,2-diaminocyclohexane tion-relevant supramolecular chemistry 763], although they did not dwell at the and diols such as fnws-l,2-cyclohex- based both on a simple crystal engineertime on the principles and broader struc- anediol and 2,3-butanediol. They have ing concept and on very simple and • tural implications of alcohol-amine com- shown that such supramolecular struc- standard substances indeed." 34
DECEMBER 11,1995 C&EN
