Novel Aromatic Boron-Nitrogen Heterocycles: Synthesis, Properties and Applications in Biomedicine and Optoelectronics

Abstract

Heterocyclic chemistry often calls for an interdisciplinary approach to research. Novel structures invite study from both a fundamental and applied standpoint, and a given scaffold may have properties relevant to synthesis, medicine, catalysis, optoelectronics, and more. In recent decades, boron compounds have become increasingly relevant in these areas, and many simple boronic heterocycles have yet to be comprehensively explored. This work first identifies synthetic strategies to make novel tricoordinate polycyclic aromatic B–N heterocycles. Then, the resulting structures are characterised structurally, using techniques such as pKa measurement, single crystal X-ray crystallography, and NMR spectroscopy. Finally, sample applications are proposed in the areas of optoelectronics and biomedicine. Chapter 2 describes the synthesis, structure, photophysical properties, and applications of a new luminescent polyaromatic boronic scaffold (DNKs). This scaffold is structurally similar to aryl-Bdan compounds, but it exhibits dramatically different properties. Preliminary synthetic methodology was developed to produce DNKs with differing phenyl and naphthyl substitution patterns in low to moderate yields across two steps. Out of a library of compounds, three DNKs were selected for detailed characterisation and study. X-ray crystallographic study of two DNKs revealed notable structural differences between these compounds and phenyl-Bdan, including markedly shortened C–N bonds and an elongated B–N bond adjacent to the carbonyl, which participated in an intramolecular hydrogen bond. Photophysical data was subsequently collected in the solution and the solid state, with moderate to high quantum yields. Compounds within the library exhibit solvatochromism and aggregation-induced emission. The fluorescence of the DNK compounds appears responsive to various chemical conditions, suggesting DNKs may have potential as a flexible, customizable molecular logic platform. A simple molecular logic model system was created in solution with 2-inputs and 2-outputs. Additionally, a proof of concept was developed for a system detecting trace boronic acid contaminants at 5-15 ppm level. This method could be useful to pharmaceutical companies concerned with difficult to detect, mutagenic synthetic intermediates in drug samples. In Chapter 3, an underexplored borazaronaphthalene isomer was envisioned as a product of an enamine cyclisation and an esterification of a boronic acid with a benzylic ketone moiety. In this novel synthetic strategy, the boronic acid is a platform for condensation with easily-accessible and cheap amine modules, generating a diverse library of new structures with aromatic isosterism. Non-classical borylation methods were necessary to produce previously unknown arylboronic building blocks. Enamine adducts could be formed by reaction with many alkyl or aryl amines and aminoalcohols, although notable failures include 1,2-aminoalcohols, aminosulfur compounds and amino acids. A representative compound was chosen for thorough characterization. Screening suggests that it is effective against methicillin-resistant S. aureus, inviting further biological study to assess its medicinal potential. Its pKa of 9 was similar to free arylboronic acids and higher than typical arylboronic cyclic esters, which could be due to partial aromatic character of the B–N containing ring. X-ray crystallographic studies revealed a highly planar structure with unusually short C–N and C–B bonds within the enamine ring, which supported the interpretation of increased π delocalization. Basic fluorometry data was collected for a few class members, which suggests fluorescence may be general for these species. The qualitative fluorescence is unique compared to naphthalenes and non-enamine phenyl-Bdan, which calls for further investigation and the collection of quantum yields.