Structure Elucidation of Pharmaceutically Relevant Compounds Within Pyrene‐Based Frameworks

• Published in: Chemistry : a European journal Vol. 30; no. 68; pp. e202402958 - n/a
• Main Authors: Chaudhry, Mohammad T., Newman, Justin A., Lee, Alfred Y., Patel, Anisha
• Format: Journal Article
• Language: English
• Published: Germany Wiley Subscription Services, Inc 05.12.2024
• Subjects: Adenosine; Aromatic compounds; Benzaldehyde; Benzaldehydes - chemistry; Benzamide; Benzamides - chemistry; Chemical bonds; Complex formation; Crystallography; Crystallography, X-Ray; Crystals; Encapsulation; Functional groups; Guanidine - chemistry; Hydrogen Bonding; Hydrogen bonds; Lidocaine; Models, Molecular; Molecular Structure; Pharmaceutical Preparations - chemistry; Pharmaceuticals; Pyrene; Pyrenes - chemistry; Structure elucidation; Thymidine; Thymine; Uracil; Workflow; X-Ray Diffraction; Pyrene; Crystallography; Structure elucidation; Pharmaceuticals
• DOI: 10.1002/chem.202402958
• ISSN: 0947-6539; 1521-3765

Single‐crystal X‐ray diffraction (SCXRD) is the preferred and most accurate technique for determining molecular structures. However, it can present challenges when dealing with specific small molecules and active pharmaceutical ingredients (APIs), as many do not form quality crystals without coformers or can be unstable. In this study, we introduce tetrakis(guanidinium) pyrenetetrasulfonate (G4PYR), a robust guanidinium‐organosulfonate (GS) framework that efficiently encapsulates small molecules and APIs rich in functional groups. The hydrogen bonding frameworks formed by G4PYR display well‐ordered structures with predictable pyrene‐pyrene distances, making them ideally suited for targeting arene‐based APIs with pendant groups. Successful encapsulation of various guests, including benzaldehyde, benzamide, and arenes containing multiple hydrogen bond donors and acceptors like uracil and thymine, was achieved. Furthermore, we successfully encapsulated important pharmaceutical and biologically relevant compounds, such as lidocaine, ropinirole, adenosine, thymidine, and others. Notably, we present a workflow for investigating host‐guest complex formation using powder X‐ray diffraction and high throughput experimentation. Using the predictable packing arrangement of guanidinium organosulfonate with a pyrene core a host of different small molecules can be encapsulated and their structures elucidated.