Electronegativity Effects on Conformational Stability Using Bent's Rule: From Simple Molecules to Acetylcholine
DOI:
https://doi.org/10.11113/mjfas.v20n5.3635Keywords:
Acetylcholine, Alzheimer’s disease, Bent’s rule, Conformational stability, DFT calculations.Abstract
Hybridization and electronegativity are fundamental concepts in chemistry connected by Bent's rule. This rule explains many aspects of the structural chemistry and reactivity of organic and inorganic compounds. Over decades, the application of Bent's rule has expanded, demonstrating its wide-ranging utility in elucidating molecular stability due to the substitution of highly electronegative atoms. This study successfully leverages Bent's rule to explain conformational energy difference in acetylcholine case using density-functional calculations. We used butane (Group 2) and butanone (Group 3) families to model the head of ACh+ and substituted one of the carbons with highly electronegative atoms: B, C, N, and O. This enabled us to evaluate the effects of electronegativity, as well as the presence of carbonyl groups, on their conformational stability and s character. There were three highlighted results. First, our calculations result in the s character are consistent with Bent's rule. Second, the high conformational energy differences can be attributed to the changes of s character in C2–Z bond: linear in Group 2 and exponential in Group 3, indicating the strong contribution of the carbonyl group. Third, the key determining factor in ACh+ conformational stability is the carbonyl group, which also strongly contributes to the solute-solvent interactions. Therefore, our study can be further applied to other similar molecules, potentially leading to broader applications in chemistry, especially for understanding ACh+ stability for Alzheimer’s Disease treatment.
References
Pauling, L. (1931). The Nature of the Chemical Bond. Application of Results Obtained from The Quantum Mechanics and From a Theory of Paramagnetic Susceptibility to the Structure of Molecules. Journal of American Chemical Society, 53, 1367–1400.
McMurry, J. (2015). Organic chemistry (9th ed.). USA: Cengage Learning.
Bent, H. A. (1960). Electronegativities from Comparison of Bond Lengths in AH and AH+. The Journal of Chemical Physics, 33(4), 1258–1259.
Bent, H. A. (1960). Correlation of Bond Shortening by Electronegative Substituents with Orbital Hybridization. The Journal of Chemical Physics, 33(4), 1259–1260.
Bent, H. A. (1960). Bond Shortening by Electronegative Substituents. The Journal of Chemical Physics, 33(4), 1260–1261.
Tantardini, C., & Oganov, A. R. (2021). Thermochemical electronegativities of the elements. Nature Communications, 12(1), 2087.
Szatyłowicz, H., & Krygowski, T. M. (2007). Varying electronegativity: Effect of the Nature and Strength of H-bonding in Anilide/Aniline/Anilinium Complexes on the Electronegativity of NH=NH2=NH3+ groups. Journal of Molecular Structure, 844–845, 200–207.
Campanelli, A. R., Domenicano, A., & Ramondo, F. (2003). Electronegativity, Resonance, and Steric Effects and the Structure of Monosubstituted Benzene Rings: An ab Initio MO Study. The Journal of Physical Chemistry A, 107(33), 6429–6440.
Wetmore, S. D., Schofield, R., Smith, D. M., & Radom, L. (2001). A Theoretical Investigation of the Effects of Electronegative Substitution on the Strength of C-H⋯N Hydrogen Bonds. The Journal of Physical Chemistry A, 105(38), 8718–8726.
Appleton, A. L., Brombosz, S. M., Barlow, S., Sears, J. S., Bredas, J. L., Marder, S. R., & Bunz, U. H. F. (2010). Effects of Electronegative Substitution on the Optical and Electronic Properties of Acenes and Diazaacenes. Nature Communications, 1, 91.
Lu, J., Jin, H., Dai, Y., Yang, K., & Huang, B. (2012). Effect of Electronegativity and Charge Balance on the Visible-Light-Responsive Photocatalytic Activity of Nonmetal Doped Anatase TiO2. International Journal of Photoenergy, 928503.
Chen, H., Yang, M., Liu, J., Lu, G., & Feng, X. (2020). Insight into effect of electronegativity on H2 catalytic activation for CO2 hydrogenation: Four transition metal cases from a DFT study. Catalysis Science & Technology, 10(16), 5641–5647.
Chen, H., Fu, W., Geng, Z., Zeng, J., & Yang, B. (2021). Inductive Effect as a Universal concept to design efficient catalysts for CO2 electrochemical reduction: electronegativity difference makes a difference. Journal of Materials Chemistry A, 9(8), 4626–4647.
Alabugin, I. V., & Manoharan, M. (2007). Rehybridization as a general mechanism for maximizing chemical and supramolecular bonding and a driving force for chemical reactions. Journal of Computational Chemistry, 28(1), 373–390.
Alabugin, I. V., Manoharan, M., Peabody, S., & Weinhold, F. (2003). Electronic Basis of Improper Hydrogen Bonding: A Subtle Balance of Hyperconjugation and Rehybridization. Journal of American Chemical Society, 125(19), 5973–5987.
Bernett, W. A. (1968). Hybridization Effects in Fluorocarbons. The Journal of Organic Chemistry, 34(6), 1772–1776.
Alabugin, I. V., Manoharan, M., Buck, M., & Clark, R. J. (2007). Substituted anilines: The tug-of-war between pyramidalization and resonance inside and outside of crystal cavities. Journal of Molecular Structure: Theochem, 813(1–3), 21–27.
Kandemirli, F., Hoscan, M., Dimoglo, A., & Esen, S. (2008). Theoretical Study and Comparison of Bent’s Rule with Hardness and Polarizability for SF4, SF4O, PCl4F, PCl3F2, PCl2F3, PCl2F4 Molecules. Phosphorus, Sulfur, and Silicon and the Related Elements, 183(8), 1954–1967.
Grabowski, S. J. (2011). Red- and Blue-Shifted Hydrogen Bonds: the Bent Rule from Quantum Theory of Atoms in Molecules Perspective. The Journal of Physical Chemistry A, 115(44), 12340–12347.
Grabowski, S. J. (2011). Theoretical study on the interconversion of silabenzenes and their monocyclic non-aromatic isomers via the [1,3]-substituent shift: Interplay of aromaticity and Bent's rule. The Journal of Physical Chemistry A, 115(45), 12789–12799.
Wang, X., Huang, Y., An, K., Fan, J., & Zhu, J. (2014). Theoretical study on the interconversion of silabenzenes and their monocyclic non-aromatic isomers via the [1,3]-substituent shift: Interplay of aromaticity and Bent's rule. Journal of Organometallic Chemistry, 770, 146–150.
Medina, J. M., Mackey, J. L., Garg, N. K., & Houk, K. N. (2014). The Role of Aryne Distortions, Steric Effects, and Charges in Regioselectivities of Aryne Reactions. Journal of The American Chemical Society, 136(44), 15798–15805.
Alabugin, I. V., Bresch, S., & Manoharan, M. (2014). Hybridization Trends for Main Group Elements and Expanding the Bent’s Rule Beyond Carbon: More than Electronegativity. The Journal of Physical Chemistry A, 118(20), 3663–3677.
Huang, Y., Wu, J., Qiu, R., Xu, F., & Zhu, J. (2020). Probing the Tautomerization of Disilenes and Disilabenzenes with Their Isomeric Silylenes: Significant Substituent, Aromaticity and Base Effects. Dalton Transactions, 49(47), 17341–17349.
Kang, D., Cheung, S. T., & Kim, J. (2021). Bioorthogonal Hydroamination of Push-Pull-Activated Linear Alkynes. Angewandte Chemie International Edition, 60(31), 16947–16952.
Zhou, W., Pan, W., Chen, J., Zhang, M., Lin, J., Cao, W., & Xiao, J. (2021). Transition-metal difluorocarbene complexes. Chemical Communications, 57(74), 9316–9329.
Izod, K., Madlool, A. M., Craig, A., & Waddell, P. G. (2022). Substituent Effects on the Structures of Alkali Metal Phosphido-Borane Complexes. European Journal of Inorganic Chemistry, 2022(15), E202200123.
Karandikar, S. S., Bhattacharjee, A., Metze, B. E., Javaly, N., Valente, E. J., McCormick, T. M., & Stuart, D. R. (2022). Orbital Analysis of Bonding in Diarylhalonium Salts and Relevance to Periodic Trends in structure and Reactivity. Chemical Science, 13(22), 6352–6540.
Pinhas, A. R., Kugel, R. W., & Jensen, W. B. (2024). Elaborating the Link Between VSEPR and Orbital Hybridization. International Journal of Chemistry, 16(1), 57.
Paul, B. K. (2024). Blue- and Red-Shifting C−H⋯O Hydrogen Bonds of Cyclic Ethers with Haloforms: Effect of Ring-Size and Consistency with Bent’s Rule. ChemPhysChem, E202400263.
Gauthier, S. (2002). Advances in the pharmacotherapy of Alzheimer’s disease. Canadian Medical Association Journal, 166(5), 616–623.
Fadilla, R. N., Rusydi, F., Aisyah, N. D., Khoirunisa, V., Dipojono, H. K., Ahmad, F., Mudasir, & Puspitasari, I. (2020). A Density-functional Study of the Conformational Preference of Acetylcholine in the Neutral Hydrolysis. Molecules, 25, 670.
Fadilla, R. N., Rusydi, F., Madinah, R., Dipojono, H. K., Ahmad, F., Mudasir, Puspitasari, I., & Morikawa, Y. (2023). Acetylcholine Conformational Flexibility and Its Neutral Hydrolysis in Aqueous Solution. ChemistrySelect, 8(15), 1–15.
Kohn, W., & Sham, L. J. (1965). Self-Consistent Equations Including Exchange and Correlation Effects. Physical Review A, 140(4A), A1133.
Hohenberg, P., & Kohn, W. (1964). Inhomogeneous Electron Gas. Physical Review, 136(3B), B864.
Rusydi, F., Madinah, R., Puspitasari, I., Fui, M. L. W., Ahmad, A., & Rusydi, A. (2021). Teaching Reaction Kinetics through Isomerization Cases with the Basis of Density-functional Calculations. Biochemistry and Molecular Biology Education, 49(2), 216–227.
Frisch, M. J., et al. (2016). Gaussian 16 Revision C.01.
Glendening, E. D., Landis, C. R., & Weinhold, F. (2013). Natural bond orbital analysis program. Journal of Computational Chemistry, 34(16), 1429–1437.
Tomasi, J., Mennucci, B., & Cammi, R. (2005). Quantum mechanical continuum solvation models. Chemical Reviews, 105(8), 2999–3093.
Young, D. C. (2001). Computational chemistry: A practical guide for applying techniques to real world problems. John Wiley & Sons.
Bradford, W. F., Fitzwater, S., & Bartell, L. S. (1977). Molecular Structure of n-Butane: Calculation of Vibrational Shrinkages and an Electron Diffraction Reinvestigation. Journal of Molecular Structure, 38, 185–194.
Oyanagi, K., & Kuchitsu, K. (1978). Molecular Structure and Conformation of Ethyl Methyl Ether as Studied by Gas Electron Diffraction. Bulletin of the Chemical Society of Japan, 51(8), 2237–2242.
Abe, M., Kuchitsu, K., & Shimanouchi, A. T. (1969). Electron-Diffraction Study of Rotational Isomerism of Methyl Ethyl Ketone. Journal of Molecular Structure, 4, 245–253.
Kitano, M., Fukuyama, T., & Kuchitsu, K. (1973). Molecular Structure of N-Metyhlacetamide as Studied by Gas Electron Diffraction. Bulletin of the Chemical Society of Japan, 46, 384–387.
Pyckhout, W., Van Alsenoy, C., & Geise, H. J. (1986). Structure of Gaseous Methyl Acetate as Determined by Joint Analysis of Electron Diffraction, Microwave and Infrared Spectroscopy, Supplemented by a Valence Force Field and Constraints from Geometry Relaxed Ab Initio Calculations. Journal of Molecular Structure, 144, 265–279.
Kang, Y. K. (2001). Ab Initio MO and Density Functional Studies on Trans and Cis Conformers of N-Methylacetamide. Journal of Molecular Structure: Theochem, 546, 183–193.
Prosen, E. J., & Rossini, F. D. (1946). Heats of Formation, Hydrogenation, and Combus-Tion of The Monoolefin Hydrocarbons Through the Hexenes, and of the Higher l-Alkenes, in the Gaseous State at 25°C. Journal of Research of the National Bureau of Standards, 36.
Ataka, S., Takeuchi, H., & Tasuni, M. (1984). Infrared Studies of the Less Stable Cis Form of N-Methylformamide and N-Methylacetamide in Low-temperature Nitrogen Matrices and Vibrational Analyses of the Trans and Cis Forms of These Molecules. Journal of Molecular Structure, 113, 147–160.
Blom, C. E., & Gunthard, H. H. (1981). Rotational Isomerism in Methyl Formate and Methyl Acetate; a Low-Temperature Matrix Infrared Study Using Thermal Molecular Beams. Chemical Physics Letters, 84(2).
Almenningen, A., Anfinsen, I. M., & Haaland, A. (1970). Electron Diffraction Studies of cis- and trans-2-Butene. Acta Chemica Scandinavica, 24, 43–49.
Tanimoto, M., Kuchitsu, K., & Morino, Y. (1969). Bond Length of Dimethylacetylene as Determined by Gas Electron Diffraction. Bulletin of the Chemical Society of Japan, 42, 2519–2523.
Haynes, W. M., Lide, D. R., & Bruno, T. J. (2017). CRC handbook of chemistry and physics (97th ed.). CRC Press.
Madinah, R., Rusydi, F., Fadilla, R. N., Khoirunisa, V., Boli, L. S. P., Saputro, A. G., Hassan, N. H., & Ahmad, A. (2023). First-Principles Study of the Dispersion Effects in the Structures and Keto-Enol Tautomerization of Curcumin. ACS Omega, 8(37), 34022–34033.
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