Proposal for the In Silico Study of the physicochemical properties of the inclusion complex of perezona with β-cyclodextrin
Creators: name: Márquez Medina, Luis Carlos
name: Escobedo González, René Gerardo
name: Chapa, Christian
Publisher: name: Zenodo
Year: 2021
Subjects: in silico
physicochemical properties
perezone
perezona
cyclodextrin
inclusion complex
HOMO
LUMO
FTIR
NMR
Thermodynamics
Biomolecules

description: <strong>Background</strong><br> Inclusion complexes (ICs) result from a stable arrangement in which one of the constituents is encapsulated in the spatial concavity of another compound. The intermolecular forces involved in the formation of these are the Van de Whaals forces as well as hydrogen bonds [1]. Indeed, natural cyclodextrins are carriers of pharmacological and nutritional interest due to their lipophilic cavity, hydrophilic sides and zero toxicity. These compounds are cyclic oligosaccharides containing 6 (α-), 7 (β-) and 8 (γ-) D-glucopyranose units with α-1,4 linkages, which causes their truncated cone shape. However, the most used to improve solubility is β-cyclodextrin (BCD) due to its dimensions [2]–[4]. As a result of its characteristics, it appears as a carrier molecule for active substances.<br> Perezona is a sesquiterpene quinone, a secondary metabolite of the genus Perezia with interesting biological properties, reported for the first time by Río de la loza [5]. Some of its attributes to highlight are its high cytotoxicity towards cancer cells, inhibition of platelet aggregation, in addition to being a cardioprotective agent [6], [7]. However, its low solubility in water represents a limiting factor to exploit its pharmacological potential [8] and no measures have been reported to solve this problem.<br> Theoretical chemistry provides mathematical correlations and models to make predictions in order to explain phenomena involving atoms, molecules and materials [9]. Recently, computational technology has improved research in theoretical chemistry by providing a platform to facilitate the calculation of molecular attributes such as molecular topology, physicochemical and spectroscopic properties, to name a few [10]. Consequently, these tools have been used in the study of drugs.<br> For the study of drugs, the similarity between the predicted results has been validated with theoretical-computational applications in contrast to experimental results [11], [12]. Specifically, the Gaussian 09 (G09) program, at a density functional theory (DFT) level using the B3LYP hybrid functional, has had considerable performance in predicting the physicochemical properties of organic molecules. Also, it allows emulating conditions in its calculations in order to get closer to the natural environments in which the study molecules are found. For example, the presence of solvents such as water comes into consideration during data computation [7],[8], [13], [14].<br> With the intention of evaluating BCD as a carrier of the slot, modeling with G09 at a TFD level with the hybrid functional B3LYP is proposed to evaluate the physicochemical properties of the CI that can be formed between the two molecules mentioned. Although the therapeutic and antineoplastic properties of perezona in cells have been demonstrated, no encapsulation measure has been proposed to improve its limited solubility. Therefore, it is important to examine the theoretical physicochemical properties of the perezone with carrier substances such as BCD, since they will help determine the stability and solubility of the array. In this project, we propose to use the theoretical-computational program G09, at a TFD level with the hybrid functional B3LYP, to model the physicochemical properties of the arrangement that the slot can take with the BCD. <strong>Overall objective</strong> Assess the theoretical physicochemical properties of the most stable IC of BCD with perezone by computational methods based on PDT with the functional hybrid B3LYP. <strong>Specific objectives</strong> To establish the conformation of the lower energy IC based on the optimization at a TFD level with functional B3LYP. To optimize the selected conformer at a TFD level with functional B3LYP considering the presence of water as a solvent. To obtain the geometric properties of the optimized structure. To determine the electronic properties of the IC based on the TFD level with functional B3LYP. To generate theoretical IC spectra at a PDT level with functional B3LYP. To deduce thermochemical properties of IC based on the spectra. <br> Theoretical-computational studies allow the behavior of matter at multiple levels to be predicted with great accuracy, even before carrying out any experiment in the laboratory. Thus, the prediction of the physicochemical properties of the CI of BCD with perezone gives rise to the assessment of its stability and solubility. This allows continuing with later stages of synthesis and testing in order to achieve a pharmacological product that exploits the therapeutic properties of perezona. <strong>Proposed methodology</strong><br> 1. Proposal of 4 spatial conformations considering the regions of potential intermolecular interaction in GaussView 05 (GV05).<br> 2. Optimization of the 4 conformations in G09 based on the TFD level and functional B3LYP.<br> 3. Selection of the conformation with the lowest conformational energy product of the optimizations.<br> 4. Optimization of the selected structure with the same level of theory and operation including SCRF simulating the aqueous medium.<br> 5. Obtaining the IR spectrum at PDT level and functional B3LYP.<br> 6. Computation of the RAMAN spectrum at the TFD level and functional B3LYP<br> 7. Obtaining the H and C NMR spectrum at the PDT and functional B3LYP level<br> 8. Determination of link length of the IC at the TFD level and functional B3LYP<br> 9. Capturing the bond angles of the IC at the TFD level and functional B3LYP<br> 10. Determination of HOMO-LUMO of the IC at the PDT level and functional B3LYP<br> 11. Computation of the Electrostatic Potential Map of the IC at the TFD level and functional B3LYP<br> 12. Determination of enthalpy and entropy of the CI based on the spectra<br> 13. Deduction of Gibbs free energy of the CI based on the spectra<br> 14. Analysis and discussion of the results<br> 15. Presentation of degree project
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