ABSTRACT
The structural features of the title compound were determined or examined by three diverse procedures: single crystal X-ray diffraction analysis, solution spectroscopic procedures and Quantum mechanical theoretical calculations. The conformational asymmetry of the macrocycle provides the opportunity to form one strong NH···OC intermolecular hydrogen bond, as well as, a number of weak CH···OC bonds. The interior of the macrocycle has short approaches for NH(...)π and NH···S. The many weak hydrogen bonds cooperate to form a very hard, robust crystal. Crystal parameters: C(18)H(22)N(2)O(6)S(2), P2(1)2(1)2(1), a = 5.108(1) Å, b = 18.948(4) Å, c = 21.029(3) Å, α = ß = γ = 90°. Quantum chemical calculations have provided a strong foundation for weak hydrogen bonds. Contrary to popular belief the present work has conclusively proved that the importance of weak hydrogen bonds are perhaps underestimated since calculations show that the energy of duplex are significantly lower then estimated from the identified hydrogen bonding.
ABSTRACT
The bihelical (figure of "infinity") topology was examined from vantages of design, crystal structures, chirality, circular dichroism (CD) studies and molecular-orbital calculations. The minimalistic design envisaged the sequential linking of cystine to the anchor diphenic acid, which proved to be a general conformational lock. The bihelical compound 4 was obtained in two steps from diphenic anhydride 1 and cystine di-OMe. The chirality of 4 arises largely from the L-cystine. The bihelical compound 5 obtained from D-cystine di-OMe was found, by X-ray crystallography, CD studies, and optical rotation, to be the perfect mirror image of 4 prepared from L-cystine. The crystal structure of prototype 8, prepared by protocols used for 4 from the achiral cystine analogue cystamine, had a "U"-shaped conformation held together by intramolecular hydrogen bonds. Analysis of 4 and 5 show that the pairs of nine-membered beta-turn-like constructs made compact through hydrogen bonding with DMSO hold the key for the bihelical conformation. Another factor is the need for the presence of a ligand at the Calpha position. The absence of this, as in 8, allows major flexibility in the torsional angles around this critical region, promoting flexible alternatives. The CD analysis of 4, confirmed to be bihelical by X-ray crystallography, showed a typical negative band at about 210 A attributed to the beta-turn-like motif, and in the positive-band region a peak at about 227 A, generally related to the twist of the biphenyl unit. The cystamine analogue 8, which showed a "U"-type structure, presented a CD spectrum with no typical features. The total energy, derived from theoretical calculations by using the X-ray structure data, support the bihelical structure for 4 and a "U"-shaped one for 8. The limited utility of such calculations was tested with composite 9. Composite 9, in which the anchor diphenic acid is linked to cystamine on the one hand and to cystine on the other, showed a CD spectrum similar to that of 4, and this coupled with molecular-orbital calculations, using data from 4 and 8, predict a bihelical structure for this compound.
Subject(s)
Macrocyclic Compounds/chemistry , Macrocyclic Compounds/chemical synthesis , Circular Dichroism , Crystallography, X-Ray , Hydrogen Bonding , Molecular StructureABSTRACT
Two possibilities exist for the evolution of individual enzymes/proteins from a milieu of amino acids, one based on preference and selectivity and the other on the basis of random events. Logic is overwhelmingly in favour of the former. By protein data base analysis and experiments, we have provided data to show the manifestation of two types of preferences, namely, the choice of the neighbour and its acceptance from the amino end (left) or the carboxyl end (right). The study tends to show that if the 20 proteinous amino acids were made to combine in water, the resulting profile would be nonrandom. Such selectivity could be a factor in protein evolution.
