Vibrational Circular Dichroism Unravels Supramolecular Chirality and Hydration Polymorphism of Nucleoside Crystals

Abstract

Vibrational circular dichroism (VCD) spectroscopy has been widely used to study (bio)molecules in solution. However, its solid-state applications have been restricted due to experimental limitations and artifacts. Having overcome some of them, the first VCD study of nucleoside crystals is now presented. A two-orders-of-magnitude enhancement of VCD signal was observed due to high molecular order in the crystals and resulting supramolecular chirality. This allowed to obtain high-quality VCD spectra within minutes using minute amounts of samples. The VCD technique is extremely sensitive in detecting changes in a crystal order and is able to distinguish different hydration states of crystals. This elevates it to a new level, as a fast and efficient tool to study chiral crystalline samples. This study demonstrates that VCD is capable of near-instantaneous detection of hydration polymorphs and crystal degradation, which is of substantial interest in pharmaceutical industry (quality and stability control).

How Crystal Symmetry Dictates Non‐Local Vibrational Circular Dichroism in the Solid State

“…In this context, chiroptical spectroscopy provides an increasingly important, cost‐effective alternative for the study of chiral solids,[ 6 , 7 , 8 , 9 , 10 ] even though it delivers only implicit information about the molecular configuration and often requires computational interpretation. In recent years, vibrational circular dichroism (VCD) has come into focus, which is a ground‐state property relying on a wealth of absorption bands (in the infrared region), many more than its electronic counterpart.…”

Fourier Transform Infrared (FTIR) Spectroscopic Study of Biofilms Formed by the Rhizobacterium Azospirillum baldaniorum Sp245: Aspects of Methodology and Matrix Composition

“…The diverse field of microbiology has been progressively developing over the last decades, largely owing to the steadily growing applications of a range of modern molecular spectroscopy techniques that provide molecular-level information on complicated microbiological objects and allow for successfully solving various bioanalytical problems, often in situ or in vivo (see, e.g., [ 1 , 2 , 3 , 4 , 5 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 , 14 , 15 , 16 , 17 ]). We would like to emphasize the informativity of very relevant vibrational spectroscopic techniques, including various modifications of infrared (conventional absorption [ 2 , 7 , 11 , 16 ], diffuse reflectance [ 3 , 6 ], attenuated total reflectance (ATR) [ 5 , 17 ] and surface-enhanced absorption [ 15 ] modes; 2D infrared [ 8 ]) and Raman [ 1 , 2 , 13 ] spectroscopies, as well as their combinations [ 4 , 14 ]; vibrational circular dichroism [ 12 ], optical activity [ 9 ], etc. Of special notice are microbiological applications of Mössbauer spectroscopy, in both transmission and emission variants [ 2 , 10 ].…”

How Crystal Symmetry Dictates Non‐Local Vibrational Circular Dichroism in the Solid State

“…In this context, chiroptical spectroscopy provides an increasingly important, cost‐effective alternative for the study of chiral solids, [6–10] even though it delivers only implicit information about the molecular configuration and often requires computational interpretation. In recent years, vibrational circular dichroism (VCD) has come into focus, which is a ground‐state property relying on a wealth of absorption bands (in the infrared region), many more than its electronic counterpart [11] .…”

“…In recent years, vibrational circular dichroism (VCD) has come into focus, which is a ground‐state property relying on a wealth of absorption bands (in the infrared region), many more than its electronic counterpart [11] . Being a very sensitive probe of molecular conformation and environment, VCD has been applied to a wide range of molecules including natural products, host‐guest systems, peptides and proteins, nanoparticles or catalysts, [12–21] supramolecular organisation in the condensed phase, [8, 22–32] and the formation of chiral phases from achiral subunits [5, 33, 34] . In particular, the utility of solid‐state VCD for the resolution of molecular chirality and supramolecular chirality has been noted by Sato and co‐workers [35–37] .…”

“… [36, 37] . Therefore, the identification of enantiomorphisms in the crystal structure—at constant IR absorption—is a key feature of solid‐state VCD, which can be used to distinguish polymorphic forms, as demonstrated in several seminal works [8, 37–40] …”