Folded Conformations Of Aromatic Amides: Force-induced Transition And A Determination Method

With the understanding of hierarchical structures and folding principles of proteins,several research groups in the 1990s started to study how to create synthetic polymers(or oligomers)with predictable three-dimensional structures.Then,a new research field of foldamers has gradually developed,including design and synthesis of molecules,characterization and adjustment of three-dimensional structures,and development of functions and applications.In this field,the research on aromatic amide foldamers is one of the principal hotspots.A variety of foldamers have been designed and constructed on the basis of intramolecular hydrogen bonding between the amide group(or urea or hydrazide)and another group on the aromatic rings.Because of the inherent coplanar tendency between adjacent building blocks and the directionality of hydrogen bonding,most of the aromatic amide foldamers possess highly predictable folded conformations.In this Ph D dissertation,we designed foldable aromatic amide molecules with simple structures.On the one hand,we studied the microscopic mechanism behind the special mechanical properties of a polyamide elastomer,and on the other hand,we proposed a new method for detecting the intramolecular hydrogen bonding of an aromatic amide based on one-dimensional NMR spectra.The main research results are described as follows.1.Study on the mechanical properties and conformational transition of a polyamide with a locally folded conformation.We synthesized a polyamide,P2M,and found that P2M could be plasticized with 2,2,2-trifluoroethanol(TFE)to obtain an elastomer.The intramolecular hydrogen bonding and folded conformation of P2M in TFE was characterized by analyzing the ¹H NMR spectra of P2M and the corresponding model molecules.The P2M elastomer displayed a fracture strain of940%as shown in the uniaxial tensile test.Interestingly,its stress-strain curve showed an unusual shape,in which a broad peak appeared at the strain of around 600%,indicating a process of energy dissipation.Moreover,we employed the steered molecular dynamics simulation to analyze hydrogen bonding and conformations of structural units of a P2M oligomer.We observed intramolecular-hydrogen-bond dissociation and conformational transition during the stretching process of a single chain.Therefore,the special mechanical properties of P2M elastomer were attributed to the microscopic conformational transition and hydrogen-bond dissociation.2.Establishment of a new method for detecting intramolecular hydrogen bonding of N-alkyl aromatic amides.Thirteen N-alkyl aromatic amides were synthesized,eight of which can form intramolecular hydrogen bonds,and the others are their reference compounds.We analyzed the solvent-related change in chemical shifts of aromatic protons at the?-positon of carbonyl groups(?H)of these compounds in chloroform,nitromethane,acetonitrile and DMSO,which is designated as?(?_?H).Based on the de-shielding effect of carbonyl groups,we proposed a new method,the?(?_?H)method,for detecting intramolecular hydrogen bonding of an aromatic amide based on one-dimensional NMR spectra,which is highly suitable for methoxy-benzamides and fluoro-benzamides in chloroform and DMSO.In addition,as for the utilization of the?(?_NH)method for detecting the intramolecular hydrogen bonding of methoxy-benzamides and pyridine-carboxamides,we recommend nitromethane and acetonitrile as possible alternatives to chloroform if a test compound is not soluble in chloroform.It is worth noting that reference compounds are not required for applying the?(?_?H)method,which is an advantage over the?(?_NH)method.3.Development of the?(?_?H)method for detecting the three-center hydrogen bonding of N-aryl aromatic amides.Besides?H of an N-aryl aromatic amide,the ortho-proton on the aniline ring(or methyl anthranilate),i.e.the?H relative to the carbonyl group,may lie in the de-shielding zone of carbonyl group.Referring to the?(?_?H)method,we combined the values of?(?_?H)and?(?_?H)to analyze the conformations of nine N-aryl aromatic amides that could form three-center hydrogen bonds and six N-aryl aromatic amides that could form two-center hydrogen bonds.Its advantage is that whether?H and?H lie in the de-shielding zone of carbonyl groups or not could be determined separately.Therefore,conformations and three-center hydrogen bonding of N-aryl aromatic amides could be analyzed in detail.It was disclosed that three aromatic amides(2-fluoro-N-(2-methoxyphenyl)benzamide,N-(2-fluorophenyl)-2-methoxybenzamide and 2-fluoro-N-(2-fluorophenyl)benzamide)display excellent planarization of molecular comformations at both sides of their amide groups,which would have greater potential in constructing new foldamers.Furthermore,it was inferred that,for an aromatic amide with a three-center hydrogen bond,two hydrogen-bond acceptors contended with each other for the NH group,resulting in a balanced situation.