Absolute Stereochemical Determination of Organic Molecules through Induction of Helicity in Host–Guest Complexes

Abstract

Metrics & MoreArticle Recommendations CONSPECTUS: Stereochemistry is a fundamental molecular property with important ramifications for structure, function, and activity of organic molecules. The basic building blocks of living organisms (amino acids and sugars) exhibit a precisely selected set of molecular handedness that has evolved over millions of years. The absolute stereochemistry of these building blocks is manifested in the structure and function of the cell machinery (e.g., enzymes, proteins, etc.), which are essential components of life. In the many chemical subdisciplines, molecular stereochemistry is exceedingly important and is often a strong determinant of structure and function. Besides its biological implications, the centrally important role of stereochemistry in many disciplines of chemistry and related fields has led to tremendous effort and activity, highlighted by the success in stereoselective syntheses of a host of functionalities. In the present climate, it is often the difficulty of assigning absolute stereochemistry as opposed to synthesis, which has become a nontrivial challenge, requiring the attention of the community. There will not be a general solution to this problem, as each system will have its own unique requirements and challenges; however, the need for rapid, routine, and microscale analysis is apparent. This is especially true with parallel and high-throughput arrays for screening conditions and catalysts, generating a large number of samples that require analysis.In this Account, we summarize our contribution to this field through the development of molecular receptors for sensing molecular asymmetry. These methodologies strive to unambiguously assign the absolute configuration of asymmetric center(s). To accomplish this task, our laboratory has designed a variety of host molecules, bearing various binding elements, to form stable complexes with chiral molecules (guests). During this complexation event, the stereochemistry of a target molecule induces a supramolecular chirality (i.e., helicity) within the host system. The design of the host system is such that the helicity of the host/guest complex can be observed and assigned via Exciton Coupled Circular Dichroism (ECCD), a nonempirical technique for identifying handedness, which is correlated back to the absolute stereochemistry of the bound chiral molecule. Taking advantage of the high sensitivity of chiroptical techniques (in terms of the required amount of sample for analysis) and fast response time, these methodologies offer a microscale, rapid, and nonempirical solution for assignment of absolute stereochemistry.The first part of this Account describes application of porphyrin tweezers as reporters of chirality for the absolute stereochemical determination of various classes of organic molecules. This methodology is suitable to report the absolute configuration of organic molecules that contain two binding elements (nitrogen or oxygen based functionalities). In the second part, host systems that do not require two sit...

Bioinspired Applications of Porphyrin Derivatives

“…Porphyrin-based molecular tweezers having positive allosterism have been utilized for chiral discrimination. − We designed a porphyrin tweezer ( 4 ) having two urea groups as a heterotropic allosteric host for carboxylates and diamine guests . Because porphyrins have high molar extinction coefficients in the visible region, molecular interactions between porphyrin units can be monitored on the basis of the changes in absorption .…”

Surfactant-induced chirality transfer, amplification and inversion in a cucurbit[8]uril–viologen host–guest supramolecular system

“…One possible way to circumvent these issues is to predesign suitable molecular structures and to utilize these components as building blocks to construct designed supramolecular architectures. For instance, a well-defined macrocycle-based host–guest system 36–39 with a specific host and guest molar ratio may provide a feasible approach to build such supramolecular structures. Cucurbit[8]uril (CB[8]) is widely used as a host molecule to produce various dynamic host–guest supramolecular systems.…”

Self-Assembly of Chiral Cyclohexanohemicucurbit[n]urils with Bis(Zn Porphyrin): Size, Shape, and Time-Dependent Binding

“…The corresponding linker(s) may provide conformational flexibility or rigidity and thus make it possible to vary the distance between corresponding cores [10][11][12][13][14][15][16]. The most exciting aspect of bis-metalloporphyrins is their ability to recognize enantiomers of various monodentate and bidentate chiral molecules [11,[17][18][19][20][21][22] related to the general phenomenon of chiral information transfer from guest to host, which is also employed by other sensing systems [23][24][25][26]. Typically, upon the host-guest interaction, a noticeably strong circular dichroism (CD) signal in the region of porphyrin absorption is induced.…”