How to easily replace the independent atom model – the example of bergenin, a potential anti-HIV agent of traditional Asian medicine

Abstract

Bergenin, which has been isolated from a variety of tropical plants, has several pharmacological applications in traditional Asian medicine. Its electron-density distribution was obtained from a room-temperature low-resolution X-ray data set measured with point detection making use of multipole populations from the invariom library. Two refinement models were considered. In a first step, positional parameters and ADPs were refined with fixed library multipoles (model E1). This model was suitable to be input into a second refinement of multipoles (model E2), which converged smoothly although based on Cu Kalpha room-temperature data. Quantitative results of a topological analysis of the electron density from both models were compared with Hartree-Fock and density-functional calculations. With respect to the independent atom model (IAM) more information can be extracted from invariom modelling, including the electrostatic potential and hydrogen-bond energies, which are highly useful, especially for biologically active compounds. The reliability of the applied invariom formalism was assessed by a comparison of bond-topological properties of sucrose, for which high-resolution multipole and invariom densities were available. Since a conventional X-ray diffraction experiment using basic equipment was combined with the easy-to-use invariom formalism, the procedure described here for bergenin illustrates how it can be routinely applied in pharmacological research.

Relationships between interaction energy, intermolecular distance and electron density properties in hydrogen bonded complexes under external electric fields

“…These dependencies are being applied in the analysis of experimental electron densities or electron densities built from crystal structure data [6], sometimes to interactions other than the hydrogen bond [7], as well as in the analysis of theoretical calculations in solid state [8]. However, there is few information about the applicability domain and accuracy of these dependencies when used as estimators of HB energies.…”

Probing Weak Intermolecular Interactions by Using the Invariom Approach: A Comparative Study ofs‐Tetrazine

“…Among other options, transferred multipolar models were developed, one of them being based on a recently introduced concept of invarioms 2. They were devised to replace an independent atom model (IAM)3, 4 by using database entries of multipolar parameters obtained within the Hansen–Coppens aspherical‐atom formalism5 from X‐ray measurements of high quality6 or from quantum chemical calculations 2. 7 As well as taking as less time than IAM to employ,8, 9 their use allows reaching the accuracy of conventional multipole refinement against high‐resolution data 8.…”

“…Having gained the popularity in the last decade, the invariom approach has already been successfully applied for describing different organic systems and helping with different chemical problems inaccessible by full experimental multipole refinement. Those include a more reliable absolute structure determination for light‐atom compounds,13 charge density studies from low (normal) resolution datasets,9, 14, 15 only collectible with copper radiation,4 and of larger molecules with poor reflective power,16 identification and treatment of a disorder,17 and so on. Thus, being an extremely promising approach, it can even use other starting geometries than from X‐ray diffraction, for example, those obtained from quantum chemistry or NMR spectroscopy 8…”

“…Numerous studies to date performed with the invariom formalism showed it to successfully reproduce features of covalent bonds18, 19 with the same accuracy as that of full multipole refinement (sometimes higher8). Although by the definition of invarioms,2 the resulting electron density does not contain the information on crystal packing effects, attempts have been made to use them for examining intermolecular interactions in organic crystals, but in all cases H‐bonds were mostly commented on 4. 12, 15, 19, 20 Their influence on molecular and crystal properties was quantified by the analysis of Hirshfeld surfaces,15, 19, 21 mapping of electrostatic potential (thus revealing important implications for drug research),4, 8, 9, 12, 15, 20, 21 or by topological features within Bader’s “Atoms in Molecules” theory (AIM) 4.…”

Electron Density Study Of The Anti-Alzheimer’s Disease Drug Donepezil From Conventional X-Ray Data And Invariom Database Application

“…This way, an ED can be provided from conventional x-ray diffraction data. Moreover, it was shown that ED properties obtained from an invariom application to a conventional x-ray data set were comparable to the corresponding results from a high-resolution multipole refinement [8,9].…”