Polymorphic Forms of Valinomycin Investigated by NMR Crystallography.

Jiří Czernek,Jiří Brus

doi:10.3390/ijms21144907

Abstract

A dodecadepsipeptide valinomycin (VLM) has been most recently reported to be a potential anti-coronavirus drug that could be efficiently produced on a large scale. It is thus of importance to study solid-phase forms of VLM in order to be able to ensure its polymorphic purity in drug formulations. The previously available solid-state NMR (SSNMR) data are combined with the plane-wave DFT computations in the NMR crystallography framework. Structural/spectroscopical predictions (the PBE functional/GIPAW method) are obtained to characterize four polymorphs of VLM. Interactions which confer a conformational stability to VLM molecules in these crystalline forms are described in detail. The way how various structural factors affect the values of SSNMR parameters is thoroughly analyzed, and several SSNMR markers of the respective VLM polymorphs are identified. The markers are connected to hydrogen bonding effects upon the corresponding (13C/15N/1H) isotropic chemical shifts of (CO, Namid, Hamid, Hα) VLM backbone nuclei. These results are expected to be crucial for polymorph control of VLM and in probing its interactions in dosage forms.

Highlights

Intense efforts are ongoing to identify treatments of the 2019 novel coronavirus (2019-nCoV) [1].For an obvious reason, it is a very quickly evolving field that was already reviewed [2,3,4]
One of the approaches to the description of polymorphic forms of drug compounds is an application of the NMR crystallography [11]
Yl-L-valyl-D-α-hydroxyisovaleryl-D-valyl-L-lactoyl-L-valyl)

Summary

Introduction

Intense efforts are ongoing to identify treatments of the 2019 novel coronavirus (2019-nCoV) [1].For an obvious reason, it is a very quickly evolving field that was already reviewed [2,3,4]. Described below) in a treatment of the 2019-nCoV This potential is assumed on the basis of the most recent report of an efficient preparation of VLM [7] and on its well-known antiviral activity [8]. We surmise that VLM may become a part of some 2019-nCoV drug formulation(s) and investigate crystalline phases of VLM. Their description furthers the understanding of the polymorphism of VLM (the ability of a solid VLM to form various crystal modifications). The polymorphism of VLM is expected to be extensive (see the recent study of a related problem of complexation-induced structural changes in VLM [9], and references cited therein) and important for the design and manufacturing of a drug formulation. One of the approaches to the description of polymorphic forms of drug compounds is an application of the NMR crystallography [11]

Methods

Results

Conclusion