Programming the Supramolecular Helical Polymerization of Dendritic Dipeptides via the Stereochemical Information of the Dipeptide

• Published in: Journal of the American Chemical Society Vol. 133; no. 13; pp. 5135 - 5151
• Main Authors: Rosen, Brad M, Peterca, Mihai, Morimitsu, Kentaro, Dulcey, Andrés E, Leowanawat, Pawaret, Resmerita, Ana-Maria, Imam, Mohammad R, Percec, Virgil
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 06.04.2011; Amer Chemical Soc
• Subjects: Chemistry; Chemistry, Multidisciplinary; Crystallography, X-Ray; Dendrimers - chemical synthesis; Dendrimers - chemistry; Dipeptides - chemical synthesis; Dipeptides - chemistry; Macromolecular Substances - chemical synthesis; Macromolecular Substances - chemistry; Models, Molecular; Physical Sciences; Protein Conformation; Science & Technology; Stereoisomerism; CONSTITUTIONAL ISOMERIC AB; SOLDIERS PRINCIPLE; INTERNAL STRUCTURE; SELF-ASSEMBLING DENDRONS; FLUID SMECTIC PHASE; CHIRAL COLUMNAR STACKS; DENDRIMERS; MAJORITY-RULES; STRUCTURAL DIVERSITY; HYBRID DENDRONS
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja200280h

Many natural biomacromolecules are homochiral and are built from constituents possessing identical handedness. The construction of synthetic molecules, macromolecules, and supramolecular structures with tailored stereochemical sequences can detail the relationship between chirality and function and provide insight into the process that leads to the selection of handedness and amplification of chirality. Dendritic dipeptides, previously reported from our laboratory, self-assemble into helical porous columns and serve as fundamental mimics of natural porous helix-forming proteins and supramolecular polymers. Herein, the synthesis of all stereochemical permutations of a self-assembling dendritic dipeptide including homochiral, heterochiral, and differentially racemized variants is reported. A combination of CD/UV−vis spectroscopy in solution and in film, X-ray diffraction, and differential scanning calorimetry studies in solid state established the role of the stereochemistry of the dipeptide on the thermodynamics and mechanism of self-assembly. It was found that the highest degree of stereochemical purity, enantiopure homochiral dendritic dipeptides, exhibits the most thermodynamically favorable self-assembly process in solution corresponding to the greatest degree of helical order and intracolumnar crystallization in solid state. Reducing the stereochemical purity of the dendritic dipeptide through heterochirality or by partially or fully racemizing the dendritic dipeptide destructively interferes with the self-assembly process. All dendritic dipeptides were shown to coassemble into single columns regardless of their stereochemistry. Because these columns exhibit no deracemization, the thermodynamic advantage of enantiopurity and homochirality suggests a mechanism for stereochemical selection and chiral amplification.