This summary condenses the main results of two OTKA projects entitled: "Chiral recognition and resolution of optically active organic ammonium salt enantiomers by chiral macrocycles" (OTKA ID number: T 01492, research period: 1995-1997, sum of OTKA support: 1800000 forints) and "Molecular recognition and separation by synthetic crown ethers containing heterocyclic subunits" (OTKA ID number: T 025071, research period: 1998-2001, sum of OTKA support: 5600000 forints). The principal investigator of both projects was Péter Huszthy (Research Group for Alkaloid Chemistry, Hungarian Academy of Sciences, H-1521 Budapest, Hungary).
Summary:Starting from relatively cheap and easily available starting materials we have prepared a number of novel chiral macrocycles (crown ethers) containing heterocyclic (pyridine, pyridone, acridine, acridone, phenazine) subunits for the purpose of studying their enantioselective complex formation with the enantiomers of protonated chiral primary organic amines. We have elaborated several methods for the synthesis of enantiomerically pure chiral diol precursors containing two methyl-, two iso-butyl- and two tert-butyl groups at both terminal carbon atoms which latters are the stereogenic centers. We have also prepared the achiral heterocyclic precursors for the chiral crown ethers by effective and straightforward methods.
The enantioselectivity of the chiral macrocycles for the enantimers of protonated chiral primary organic amines was studied thoroughly with 1H NMR, circular dichroism, UV/visible and luminescence spectroscopies, mass spectrometry and X-ray diffractometry. Based on these studies we identified the main intermolecular attractive (hydrogen bonding, π-π interection) and repulsive (steric strain between non-bonding atoms) weak forces which are responsible for the degree of enantioselectivity.
A pyridino-18-crown-6 ligand containing a long lipophilic hydrocarbon chain was incorporated into a plasticized PVC based electrode and we have shown that this enantioselective electrode discriminates between the enantiomers of protonated chiral primary organic amines.
A few enantiomerically pure chiral crown ethers were selected and tailored by such linkers which made possible these ligands attach covalently to solid supports (to silica gel and Merriefield-type polymer resin, for example). The chiral stationary phases so obtained separated several racemic protonated chiral primary organic amines efficiently by column chromatography.
We also prepared lipophilic proton-ionizable pyridono-18-crown-6 type ethers incorporated electron-withdrawing substituents (Br, NO2) into the pyridone subcyclic unit. These ligands have pKa values as low as 6, so they can transport almost any metal ion through aqueous source phase/organic bulk membrane/aqueous receiving phase systems at physiological pH range by the energetically favourable fashion when the original counter anion does not accompany the cation-ligand anion complex.
From the results summarized above 26 papers have been published in international journals.