A Competition between Relative Stability and Binding Energy in Caffeine Phenyl-Glucose Aggregates: Implications in Biological Mechanisms
Hydrogen bonds and stacking interactions are pivotal in biological mechanisms, although their proper characterisation within a molecular complex remains a difficult task. We used quantum mechanical calculations to characterise the complex between caffeine and phenyl-β-D-glucopyranoside, in which sev...
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MDPI AG
2023-02-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/24/5/4390 |
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| author | Camilla Calabrese Ander Camiruaga Maider Parra-Santamaria Luca Evangelisti Sonia Melandri Assimo Maris Imanol Usabiaga José A. Fernandez |
| author_facet | Camilla Calabrese Ander Camiruaga Maider Parra-Santamaria Luca Evangelisti Sonia Melandri Assimo Maris Imanol Usabiaga José A. Fernandez |
| author_sort | Camilla Calabrese |
| collection | DOAJ |
| description | Hydrogen bonds and stacking interactions are pivotal in biological mechanisms, although their proper characterisation within a molecular complex remains a difficult task. We used quantum mechanical calculations to characterise the complex between caffeine and phenyl-β-D-glucopyranoside, in which several functional groups of the sugar derivative compete with each other to attract caffeine. Calculations at different levels of theory (M06-2X/6-311++G(d,p) and B3LYP-ED=GD3BJ/def2TZVP) agree to predict several structures similar in stability (relative energy) but with different affinity (binding energy). These computational results were experimentally verified by laser infrared spectroscopy, through which the caffeine·phenyl-β-D-glucopyranoside complex was identified in an isolated environment, produced under supersonic expansion conditions. The experimental observations correlate with the computational results. Caffeine shows intermolecular interaction preferences that combine both hydrogen bonding and stacking interactions. This dual behaviour had already been observed with phenol, and now with phenyl-β-D-glucopyranoside, it is confirmed and maximised. In fact, the size of the complex’s counterparts affects the maximisation of the intermolecular bond strength because of the conformational adaptability given by the stacking interaction. Comparison with the binding of caffeine within the orthosteric site of the A2A adenosine receptor shows that the more strongly bound caffeine·phenyl-β-D-glucopyranoside conformer mimics the interactions occurring within the receptor. |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-11T07:23:17Z |
| publishDate | 2023-02-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-1f3ab597039f413380779f14f35bc6662023-11-17T07:47:50ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672023-02-01245439010.3390/ijms24054390A Competition between Relative Stability and Binding Energy in Caffeine Phenyl-Glucose Aggregates: Implications in Biological MechanismsCamilla Calabrese0Ander Camiruaga1Maider Parra-Santamaria2Luca Evangelisti3Sonia Melandri4Assimo Maris5Imanol Usabiaga6José A. Fernandez7Departamento de Química Física y Química Inorgánica, Facultad de Ciencias—I.U. CINQUIMA, Universidad de Valladolid, E-47011 Valladolid, SpainInstitut des Sciences Moléculaires d’Orsay (ISMO), UMR8214, Université Paris-Saclay, CNRS, Bat. 520, F-91405 Orsay, FranceDepartamento de Química Física, Facultad de Ciencias y Tecnología, Universidad del País Vasco (UPV/EHU), Barrio Sarriena s/N, E-48940 Leioa, SpainDipartimento di Chimica “Giacomo Ciamician”, Campus of Ravenna, Università di Bologna, Via Sant’Alberto, 163, 48123 Ravenna, ItalyDipartimento di Chimica “Giacomo Ciamician”, Università di Bologna, Via Selmi, 2, 40126 Bologna, ItalyDipartimento di Chimica “Giacomo Ciamician”, Università di Bologna, Via Selmi, 2, 40126 Bologna, ItalyDepartamento de Química Física, Facultad de Ciencias y Tecnología, Universidad del País Vasco (UPV/EHU), Barrio Sarriena s/N, E-48940 Leioa, SpainDepartamento de Química Física, Facultad de Ciencias y Tecnología, Universidad del País Vasco (UPV/EHU), Barrio Sarriena s/N, E-48940 Leioa, SpainHydrogen bonds and stacking interactions are pivotal in biological mechanisms, although their proper characterisation within a molecular complex remains a difficult task. We used quantum mechanical calculations to characterise the complex between caffeine and phenyl-β-D-glucopyranoside, in which several functional groups of the sugar derivative compete with each other to attract caffeine. Calculations at different levels of theory (M06-2X/6-311++G(d,p) and B3LYP-ED=GD3BJ/def2TZVP) agree to predict several structures similar in stability (relative energy) but with different affinity (binding energy). These computational results were experimentally verified by laser infrared spectroscopy, through which the caffeine·phenyl-β-D-glucopyranoside complex was identified in an isolated environment, produced under supersonic expansion conditions. The experimental observations correlate with the computational results. Caffeine shows intermolecular interaction preferences that combine both hydrogen bonding and stacking interactions. This dual behaviour had already been observed with phenol, and now with phenyl-β-D-glucopyranoside, it is confirmed and maximised. In fact, the size of the complex’s counterparts affects the maximisation of the intermolecular bond strength because of the conformational adaptability given by the stacking interaction. Comparison with the binding of caffeine within the orthosteric site of the A2A adenosine receptor shows that the more strongly bound caffeine·phenyl-β-D-glucopyranoside conformer mimics the interactions occurring within the receptor.https://www.mdpi.com/1422-0067/24/5/4390caffeinesugarsquantum mechanical calculationsUV/IR spectroscopynoncovalent interactions |
| spellingShingle | Camilla Calabrese Ander Camiruaga Maider Parra-Santamaria Luca Evangelisti Sonia Melandri Assimo Maris Imanol Usabiaga José A. Fernandez A Competition between Relative Stability and Binding Energy in Caffeine Phenyl-Glucose Aggregates: Implications in Biological Mechanisms International Journal of Molecular Sciences caffeine sugars quantum mechanical calculations UV/IR spectroscopy noncovalent interactions |
| title | A Competition between Relative Stability and Binding Energy in Caffeine Phenyl-Glucose Aggregates: Implications in Biological Mechanisms |
| title_full | A Competition between Relative Stability and Binding Energy in Caffeine Phenyl-Glucose Aggregates: Implications in Biological Mechanisms |
| title_fullStr | A Competition between Relative Stability and Binding Energy in Caffeine Phenyl-Glucose Aggregates: Implications in Biological Mechanisms |
| title_full_unstemmed | A Competition between Relative Stability and Binding Energy in Caffeine Phenyl-Glucose Aggregates: Implications in Biological Mechanisms |
| title_short | A Competition between Relative Stability and Binding Energy in Caffeine Phenyl-Glucose Aggregates: Implications in Biological Mechanisms |
| title_sort | competition between relative stability and binding energy in caffeine phenyl glucose aggregates implications in biological mechanisms |
| topic | caffeine sugars quantum mechanical calculations UV/IR spectroscopy noncovalent interactions |
| url | https://www.mdpi.com/1422-0067/24/5/4390 |
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