Abstract

While RNA’s 2′ hydroxyl group has long been recognized as a primary contributor to mRNA instability, owing to its heightened susceptibility to hydrolytic cleavage, this manuscript introduces a complementary quantum-biological hypothesis. It explores how vibrational modes, quantum coherence, and electromagnetic coupling influence nucleotide behavior through dynamic, real-time quantized boundary formation, governed by conservation principles such as E = mc² and E = hf.

Crucially, protonation states modulated by pKa transitions amplify local energy fluctuations, fostering transient configurations in mRNA. These instabilities are further shaped by van der Waals (vdW) interactions and the anisotropic nature of three-dimensional molecular geometry, which modulate proximity-dependent quantum effects in a context-sensitive manner. Drawing inspiration from Bohm’s implicate order, the study proposes that mRNA’s transience reflects a divergent conformational landscape, continuously perturbed by quantum-level variability. In contrast, DNA’s relative resilience is attributed to its helical architecture and robust repair mechanisms.

Building on this framework, the manuscript challenges conventional paradigms by advancing a quantum-biological model to explain both the inherent instability of natural mRNA and the enhanced stability of its N1-methylpseudouridine (m1Ψ)-modified variant. It reconceptualizes nucleotide resilience through the lens of vibrational dynamics, quantum coherence, and electromagnetic interactions, integrated with classical physical principles.

The study further investigates how m1Ψ influences polarity, folding, and base stacking in therapeutic mRNA. Although structurally analogous to thymidine in DNA rather than uridine, m1Ψ does not achieve full energetic equivalence. The central hypothesis, bridging quantum physics and molecular biology, is that m1Ψ must confer stabilizing effects comparable to thymidine, mitigating quantum-scale fluctuations through emergent structural coherence.

The pivotal question remains: is N1-methylpseudouridine a functionally equivalent substitute for uridine in therapeutic contexts?

References

1. Alberts, B., Johnson, A., Lewis, J., Raff, M., Roberts, K., & Walter, P. (2002). Molecular biology of the cell (4th ed.). Garland Science.
2. Berg, J. M., Tymoczko, J. L., Gatto, G. J., & Stryer, L. (2015). Biochemistry (8th ed.). W. H. Freeman.
3. Yu, Z., & Cowan, J. A. (1999). Human DNA repair systems: An overview. Environmental and Molecular Mutagenesis, 33(1), 3–20. https://doi.org/10.1002/(sici)1098-2280(1999)33:1<3::aid-em2>3.0.co;2-l
4. Santiago, D. (2025). A quantum timing change: Codon energetics [Preprint]. https://doi.org/10.20944/preprints202503.0548.v2
5. Lambert, N., Chen, Y.-N., Cheng, Y.-C., Li, C.-M., Chen, G.-Y., & Nori, F. (2013). Quantum biology. Nature Physics, 9(1), 10–18. https://doi.org/10.1038/nphys2474
6. Bohm, D. (1980). Wholeness and the implicate order. Routledge.
7. Engel, G. S., Calhoun, T. R., Read, E. L., Ahn, T.-K., Mancal, T., Cheng, Y.-C., Blankenship, R. E., & Fleming, G. R. (2007). Evidence for wavelike energy transfer through quantum coherence in photosynthetic systems. Nature, 446(7137), 782–786. https://doi.org/10.1038/nature05678
8. Peirce, C. S. (1863). The chemical theory of interpenetration. American Journal of Science, s2-35(103), 78–82. https://doi.org/10.2475/ajs.s2-35.103.78
9. Fenter, P., & Lee, S. S. (2014). Hydration layer structure at solid–water interfaces. MRS Bulletin, 39(12), 1056–1061. https://doi.org/10.1557/mrs.2014.252
10. Pietruszka, M., & Marzec, M. (2024). Ultra-weak photon emission from DNA. Scientific reports, 14(1), 28915. https://doi.org/10.1038/s41598-024-80469-0
11. Santiago, D. (2024). A Closer Look at N1-methylpseudouridine in the modified mRNA injectables. International Journal of Vaccine Theory, Practice, and Research, 3(2), 1345–1366. https://doi.org/10.56098/5azda593
12. Klinman, J. P., & Kohen, A. (2013). Hydrogen tunneling links protein dynamics to enzyme catalysis. Annual Review of Biochemistry, 82, 471–496. https://doi.org/10.1146/annurev-biochem-051710-133623
13. González-Jiménez, M., Ramakrishnan, G., Tukachev, N. V., Senn, H. M., & Wynne, K. (2021). Low-frequency vibrational modes in G-quadruplexes reveal the mechanical properties of nucleic acids. Physical Chemistry Chemical Physics, 23(23), 13250–13260. https://doi.org/10.1039/D0CP05404F
14. Jiang, Y., & Wang, L. (2019). Development of Vibrational Frequency Maps for Nucleobases. The journal of physical chemistry. B, 123(27), 5791–5804. https://doi.org/10.1021/acs.jpcb.9b04633
15. Bothma, J. P., Gilmore, J. B., & McKenzie, R. H. (2010). The role of quantum effects in proton transfer reactions in enzymes: Quantum tunneling in a noisy environment? New Journal of Physics, 12(5), Article 055002. https://doi.org/10.1088/1367-2630/12/5/055002
16. Bruening, E. M., Schauss, J., Siebert, T., Fingerhut, B. P., & Elsaesser, T. (2018). Vibrational Dynamics and Couplings of the Hydrated RNA Backbone: A Two-Dimensional Infrared Study. The Journal of Physical Chemistry Letters, 9(3), 583–587. https://doi.org/10.1021/acs.jpclett.7b03314
17. Heidari, A. (2016). An analytical and computational infrared spectroscopic review of vibrational modes in nucleic acids. Austin Journal of Analytical and Pharmaceutical Chemistry, 3(1), Article 1058.
18. Owens, A., Support, S. A., & IDT. (n.d.). Unraveling RNA: The importance of a 2’ hydroxyl | IDT. Integrated DNA Technologies. Retrieved July 13, 2025, from https://www.idtdna.com/pages/education/decoded/article/unraveling-rna-the-importance-of-a-2-hydroxyl
19. Jiang, Y., & Wang, L. (2020). Modeling the vibrational couplings of nucleobases. The Journal of chemical physics, 152(8), 084114. https://doi.org/10.1063/1.5141858 (Zambito, L. Research. Wang Research Group, Department of Chemistry and Chemical Biology | Rutgers, The State University of New Jersey. Retrieved July 11, 2025, from https://wanggroup.rutgers.edu/research)
20. Peng, C. S., Jones, K. C., & Tokmakoff, A. (2011). Anharmonic vibrational modes of nucleic acid bases revealed by 2D IR spectroscopy. Journal of the American Chemical Society, 133(39), 15650–15660. https://doi.org/10.1021/ja205636h
21. Aamouche, A., Ghomi, M., Letellier, R., Liquier, J., Morvan, F., Cadet, J., & Taillandier, E. (1995). Neutron inelastic scattering, optical spectroscopies and scaled quantum mechanical force fields for analysing the vibrational dynamics of pyrimidine nucleic acid bases: Uracil, thymine and cytosine. In J. C. Merlin, S. Turrell, & J. P. Huvenne (Eds.), Spectroscopy of biological molecules (pp. 493–494). Springer. https://doi.org/10.1007/978-94-011-0371-8_139
22. Parr, C. J. C., Wada, S., Kotake, K., Kameda, S., Matsuura, S., Sakashita, S., Park, S., Sugiyama, H., Kuang, Y., & Saito, H. (2020). N1-methylpseudouridine substitution enhances the performance of synthetic mRNA switches in cells. Nucleic Acids Research, 48(6), Article e35. https://doi.org/10.1093/nar/gkaa070
23. Nance, K. D., & Meier, J. L. (2021). Modifications in an emergency: The role of N1-methylpseudouridine in COVID-19 vaccines. ACS Central Science, 7(5), 748–756. https://doi.org/10.1021/acscentsci.1c00197
24. Finol, E., Krul, S. E., Hoehn, S. J., Lyu, X., & Crespo-Hernández, C. E. (2024). The mRNACalc webserver accounts for the N1-methylpseudouridine hypochromicity to enable precise nucleoside-modified mRNA quantification. Molecular therapy. Nucleic acids, 35(2), 102171. https://doi.org/10.1016/j.omtn.2024.102171
25. Morais, P., Adachi, H., & Yu, Y.-T. (2021). The Critical Contribution of Pseudouridine to mRNA COVID-19 Vaccines. Frontiers in Cell and Developmental Biology, 9. https://doi.org/10.3389/fcell.2021.789427
26. Kim, Y., Bertagna, F., D’Souza, E. M., Heyes, D. J., Johannissen, L. O., Nery, E. T., Pantelias, A., Sanchez-Pedreño Jimenez, A., Slocombe, L., Spencer, M. G., Al-Khalili, J., Engel, G. S., Hay, S., Hingley-Wilson, S. M., Jeevaratnam, K., Jones, A. R., Kattnig, D. R., Lewis, R., Sacchi, M., ... McFadden, J. (2021). Quantum Biology: An Update and Perspective. Quantum Reports, 3(1), 80-126. https://doi.org/10.3390/quantum3010006
27. Kurian, P., Dunston, G., & Lindesay, J. (2016). How quantum entanglement in DNA synchronizes double-strand breakage by type II restriction endonucleases. Journal of theoretical biology, 391, 102–112. https://doi.org/10.1016/j.jtbi.2015.11.018
28. Manzano, Daniel (2020). "A short introduction to the Lindblad master equation". AIP Advances. 10 (2): 025106. arXiv:1906.04478. Bibcode:2020AIPA...10b5106M. doi:10.1063/1.5115323. S2CID 184487806.
29. Lindblad, G. On the generators of quantum dynamical semigroups. Commun. Math. Phys. 48, 119–130 (1976). https://doi.org/10.1007/BF01608499
30. Pollack, G. H. (2013). The fourth phase of water: Beyond solid, liquid, and vapor. Ebner & Sons.
31. Andries, O., Mc Cafferty, S., De Smedt, S. C., Weiss, R., Sanders, N. N., & Kitada, T. (2015). N¹-methylpseudouridine-incorporated mRNA outperforms pseudouridine-incorporated mRNA by providing enhanced protein expression and reduced immunogenicity in mammalian cell lines and mice. Journal of Controlled Release, 217, 337–344. https://doi.org/10.1016/j.jconrel.2015.08.051
32. Chen, S., Liu, Z., Cai, J., Li, H., & Qiu, M. (2024). N1-methylpseudouridine modification level correlates with protein expression, immunogenicity, and stability of mRNA. MedComm, 5(9), Article e691. https://doi.org/10.1002/mco2.691
33. Bhattacharjee, B., Lu, P., Monteiro, V. S., Tabachnikova, A., Wang, K., Hooper, W. B., Bastos, V., Greene, K., Sawano, M., Guirgis, C., Tzeng, T. J., Warner, F., Baevova, P., Kamath, K., Reifert, J., Hertz, D., Dressen, B., Tabacof, L., Wood, J., … Iwasaki, A. (2025). Immunological and Antigenic Signatures Associated with Chronic Illnesses after COVID-19 Vaccination (p. 2025.02.18.25322379). medRxiv. https://doi.org/10.1101/2025.02.18.25322379
34. Kierzek, E., Malgowska, M., Lisowiec, J., Turner, D. H., Gdaniec, Z., & Kierzek, R. (2014). The contribution of pseudouridine to stabilities and structure of RNAs. Nucleic acids research, 42(5), 3492–3501. https://doi.org/10.1093/nar/gkt1330
35. Schnappinger, T., Falvo, C., & Kowalewski, M. (2024). Disentangling collective coupling in vibrational polaritons with double quantum coherence spectroscopy. The Journal of Chemical Physics, 161(24), 244107. https://doi.org/10.1063/5.0239877
36. Davis D. R. (1995). Stabilization of RNA stacking by pseudouridine. Nucleic acids research, 23(24), 5020–5026. https://doi.org/10.1093/nar/23.24.5020
37. Jalilvand, S., & Mousavi, H. (2024). Vibration spectra of DNA and RNA segments. European Biophysics Journal, 53, 95–109. https://doi.org/10.1007/s00249-023-01699-0
38. Mulroney, T. E., Pöyry, T., Yam-Puc, J. C., Rust, M., Harvey, R. F., Kalmar, L., Horner, E., Booth, L., Ferreira, A. P., Stoneley, M., Sawarkar, R., Mentzer, A. J., Lilley, K. S., Smales, C. M., von der Haar, T., Turtle, L., Dunachie, S., Klenerman, P., Thaventhiran, J. E. D., & Willis, A. E. (2024). N1-methylpseudouridylation of mRNA causes +1 ribosomal frameshifting. Nature, 625(7993), 189–194. https://doi.org/10.1038/s41586-023-06800-3
39. Adam, J., Adamczyk, L., Adams, J. R., Adkins, J. K., Agakishiev, G., Aggarwal, M. M., Ahammed, Z., Alekseev, I., Anderson, D. M., Aparin, A., Aschenauer, E. C., Ashraf, M. U., Atetalla, F. G., Attri, A., Averichev, G. S., Bairathi, V., Barish, K., Behera, A., Bellwied, R., … Zyzak, M. (2021). Measurement of e^+e^- Momentum and Angular Distributions from Linearly Polarized Photon Collisions. Phys. Rev. Lett., 127(5), 052302. https://doi.org/10.1103/PhysRevLett.127.052302
40. He, X., Gong, Y., Xie, F., Wang, Y., Dong, D., Li, Y., & Zhang, Z. (2023). RNA degformer: accurate prediction of mRNA degradation at nucleotide resolution with deep learning. Briefings in Bioinformatics, 24(1), bbac581. https://doi.org/10.1093/bib/bbac581
41. Irrgang, P., Gerling, J., Kocher, K., Lapuente, D., Steininger, P., Habenicht, K., Wytopil, M., Beileke, S., Schäfer, S., Zhong, J., Ssebyatika, G., Krey, T., Falcone, V., Schülein, C., Peter, A. S., Nganou-Makamdop, K., Hengel, H., Held, J., Bogdan, C., Überla, K., … Tenbusch, M. (2023). Class switch toward noninflammatory, spike-specific IgG4 antibodies after repeated SARS-CoV-2 mRNA vaccination. Science immunology, 8(79), eade2798. https://doi.org/10.1126/sciimmunol.ade2798
42. Valk, A. M., Keijser, J. B. D., van Dam, K. P. J., Stalman, E. W., Wieske, L., Steenhuis, M., Kummer, L. Y. L., Spuls, P. I., Bekkenk, M. W., Musters, A. H., Post, N. F., Bosma, A. L., Horváth, B., Hijnen, D. J., Schreurs, C. R. G., van Kempen, Z. L. E., Killestein, J., Volkers, A. G., Tas, S. W., Boekel, L., … T2B! Immunity against SARS‐CoV‐2 study group (2024). Suppressed IgG4 class switching in dupilumab- and TNF inhibitor-treated patients after mRNA vaccination. Allergy, 79(7), 1952–1961. https://doi.org/10.1111/all.16089
43. Brogna, C., Cristoni, S., Marino, G., Montano, L., Viduto, V., Fabrowski, M., Lettieri, G., & Piscopo, M. (2023). Detection of recombinant Spike protein in the blood of individuals vaccinated against SARS-CoV-2: Possible molecular mechanisms. Proteomics. Clinical applications, e2300048. Advance online publication. https://doi.org/10.1002/prca.202300048
44. Bansal, S., Perincheri, S., Fleming, T., Poulson, C., Tiffany, B., Bremner, R. M., & Mohanakumar, T. (2021). Cutting Edge: Circulating Exosomes with COVID Spike Protein Are Induced by BNT162b2 (Pfizer-BioNTech) Vaccination prior to Development of Antibodies: A Novel Mechanism for Immune Activation by mRNA Vaccines. Journal of immunology (Baltimore, Md.: 1950), 207(10), 2405–2410. https://doi.org/10.4049/jimmunol.2100637
45. Kim, S. C., Sekhon, S. S., Shin, W.-R., Ahn, G., Cho, B.-K., Ahn, J.-Y., & Kim, Y.-H. (2022). Modifications of mRNA vaccine structural elements for improving mRNA stability and translation efficiency. Molecular & Cellular Toxicology, 18(1), 1–8. https://doi.org/10.1007/s13273-021-00171-4
46. Monroe, J., Eyler, D. E., Mitchell, L., Deb, I., Bojanowski, A., Srinivas, P., Dunham, C. M., Roy, B., Frank, A. T., & Koutmou, K. S. (2024). N1-Methylpseudouridine and pseudouridine modifications modulate mRNA decoding during translation. Nature communications, 15(1), 8119. https://doi.org/10.1038/s41467-024-51301-0
47. Dutta, N., Deb, I., Sarzynska, J., & Lahiri, A. (2023). Structural and thermodynamic consequences of base pairs containing pseudouridine and N1-methylpseudouridine in RNA duplexes. bioRxiv, 2023.03.19.533340. https://doi.org/10.1101/2023.03.19.533340
48. Riback JA, Eeftens JM, Lee DSW, Quinodoz SA, Donlic A, Orlovsky N, Wiesner L, Beckers L, Becker LA, Strom AR, Rana U, Tolbert M, Purse BW, Kleiner R, Kriwacki R, Brangwynne CP. Viscoelasticity and advective flow of RNA underlies nucleolar form and function. Mol Cell. 2023 Sep 7;83(17):3095-3107.e9. doi: 10.1016/j.molcel.2023.08.006. PMID: 37683610; PMCID: PMC11089468.
49. Balani, K., Verma, V., Agarwal, A., & Narayan, R.J. (2015). Physical, Thermal, and Mechanical Properties of Polymers. doi:10.1002/9781118950623.APP1 https://api.semanticscholar.org/CorpusID:136705313
50. Roe, B.A. & Tsen, H.Y. (1977). Role of Ribothymidine in Mammalian tRNAPhe. Proceedings of the National Academy of Sciences USA, 74(9), 3696–3700.
51. Zhao, Y. H., Abraham, M. H., & Zissimos, A. M. (2003). Fast Calculation of van der Waals Volume as a Sum of Atomic and Bond Contributions and Its Application to Drug Compounds. The Journal of Organic Chemistry, 68(19), 7368–7373. https://doi.org/10.1021/jo034808o
52. Jones, E. L., Mlotkowski, A. J., Hebert, S. P., Schlegel, H. B., & Chow, C. S. (2022). Calculations of pKa Values for a Series of Naturally Occurring Modified Nucleobases. The Journal of Physical Chemistry A, 126(9), 1518–1529. https://doi.org/10.1021/acs.jpca.1c10905
53. National Center for Biotechnology Information (2025). PubChem Compound Summary for CID 99543, N1-Methylpseudouridine. Retrieved July 21, 2025 from https://pubchem.ncbi.nlm.nih.gov/compound/N1-Methylpseudouridine.
54. Hermann, J., & Tkatchenko, A. (2020). Density Functional Model for van der Waals Interactions: Unifying Many-Body Atomic Approaches with Nonlocal Functionals. Physical review letters, 124(14), 146401. https://doi.org/10.1103/PhysRevLett.124.146401
55. Seneff, S., Nigh, G., Kyriakopoulos, A. M., & McCullough, P. A. (2022). Innate immune suppression by SARS-CoV-2 mRNA vaccinations: The role of G-quadruplexes, exosomes, and MicroRNAs. Food and Chemical Toxicology, 164, 113008. https://doi.org/10.1016/j.fct.2022.113008
56. Demongeot, J.; Fougère, C. mRNA COVID-19 Vaccines—Facts and Hypotheses on Fragmentation and Encapsulation. Vaccines 2023, 11, 40. https://doi.org/10.3390/ vaccines11010040
57. Press release: The Nobel Prize in Chemistry 2024. (n.d.). NobelPrize.Org. Retrieved July 24, 2025, from https://www.nobelprize.org/prizes/chemistry/2024/press-release/
58. Brookes, J. C. (2017). Quantum effects in biology: golden rule in enzymes, olfaction, photosynthesis and magnetodetection. Proceedings. Mathematical, physical, and engineering sciences, 473(2201), 20160822. https://doi.org/10.1098/rspa.2016.0822
59. Celebi Torabfam, G., K Demir, G., & Demir, D. (2023). Quantum tunneling time delay investigation of KK+ ion in human telomeric G-quadruplex systems. Journal of biological inorganic chemistry : JBIC: a publication of the Society of Biological Inorganic Chemistry, 28(2), 213–224. https://doi.org/10.1007/s00775-022-01982-z
60. McKernan, K., Kyriakopoulos, A. M., & McCullough, P. A. (2021, November 25). Differences in Vaccine and SARS-CoV-2 Replication Derived mRNA: Implications for Cell Biology and Future Disease. https://doi.org/10.31219/osf.io/bcsa6 McKernan, K., Kyriakopoulos, A. M., & McCullough, P. A. (2021, November 25). Differences in Vaccine and SARS-CoV-2 Replication Derived mRNA: Implications for Cell Biology and Future Disease. https://doi.org/10.31219/osf.io/bcsa6
61. Bhattacharyya, D., Mirihana Arachchilage, G., & Basu, S. (2016). Metal Cations in G-Quadruplex Folding and Stability. Front. Chem., 4, 38. https://doi.org/10.3389/fchem.2016.00038
62. Wang, Y.-T., Tang, J.-S., Wei, Z.-Y., Yu, S., Ke, Z.-J., Xu, X.-Y., Li, C.-F., & Guo, G.-C. (2017). Directly Measuring the Degree of Quantum Coherence using Interference Fringes. Phys. Rev. Lett., 118(2), 020403. https://doi.org/10.1103/PhysRevLett.118.020403
63. Geesink, H., Jerman, I., & Meijer, D. K. F. (2020). The cradle of life: WATER via its coherent quantum frequencies. WATER Journal, 11, Article 1. https://doi.org/10.14294/water.2020.1
64. Montagnier, L., Del Giudice, E., Aïssa, J., Lavallee, C., Motschwiller, S., Capolupo, A., … Vitiello, G. (2015). Transduction of DNA information through water and electromagnetic waves. Electromagnetic Biology and Medicine, 34(2), 106–112. https://doi.org/10.3109/15368378.2015.1036072
65. Ho, L. L. Y., Schiess, G. H. A., Miranda, P., Weber, G., & Astakhova, K. (2024). Pseudouridine and N1-methylpseudouridine as potent nucleotide analogues for RNA therapy and vaccine development. RSC Chem. Biol., 5(5), 418–425. https://doi.org/10.1039/D4CB00022F
66. Winkler, M., Giuliano, B. M., & Caselli, P. (2020). UV Resistance of Nucleosides: An Experimental Approach. ACS Earth and Space Chemistry, 4(11), 2320–2326. https://doi.org/10.1021/acsearthspacechem.0c00228
67. Cavaluzzi, M. J., & Borer, P. N. (2004). Revised UV extinction coefficients for nucleoside‐5′‐monophosphates and unpaired DNA and RNA. Nucleic Acids Research, 32(1), e13. https://doi.org/10.1093/nar/gnh015
68. Lai, H. & Levitt, B. (2024). Cellular and molecular effects of non-ionizing electromagnetic fields. Reviews on Environmental Health, 39(3), 519-529. https://doi.org/10.1515/reveh-2023-0023
69. Sun, G., Li, J., Zhou, W., Hoyle, R. G., & Zhao, Y. (2022). Electromagnetic interactions in regulations of cell behaviors and morphogenesis. Front. Cell Dev. Biol., 10, 1014030. https://doi.org/10.3389/fcell.2022.1014030
70. Perez, F. P., Bandeira, J. P., Perez Chumbiauca, C. N., Lahiri, D. K., Morisaki, J., & Rizkalla, M. (2022). Multidimensional insights into the repeated electromagnetic field stimulation and biosystems interaction in aging and age-related diseases. Journal of Biomedical Science, 29(1), 39. https://doi.org/10.1186/s12929-022-00825-y
71. Bittner, E. R., Madalan, A., Czader, A., & Roman, G. (2012). Quantum origins of molecular recognition and olfaction in drosophila. The Journal of Chemical Physics, 137(22), 22A551. https://doi.org/10.1063/1.4767067
72. Zefirov, Y. V., & Zorkii, P. M. (1989). Van der Waals radii and their application in chemistry. Russian Chemical Reviews, 58(5), 421. https://doi.org/10.1070/RC1989v058n05ABEH003451
73. Bondi, A. (1964). Van der Waals Volumes and Radii. The Journal of Physical Chemistry, 68(3), 441–451. https://doi.org/10.1021/j100785a001
74. Wolken, J. K., & Ture ek, F. (2000). Proton affinity of uracil. A computational study of protonation sites. Journal of the American Society for Mass Spectrometry, 11(12), 1065–1071. https://doi.org/10.1016/s1044-0305(00)00176-8
75. Pinheiro PSM, Franco LS, Fraga CAM. The Magic Methyl and Its Tricks in Drug Discovery and Development. Pharmaceuticals (Basel). 2023 Aug 15;16(8):1157. doi: 10.3390/ph16081157. PMID: 37631072; PMCID: PMC10457765.
76. Barreiro EJ, Kümmerle AE, Fraga CA. The methylation effect in medicinal chemistry. Chem Rev. 2011 Sep 14;111(9):5215-46. doi: 10.1021/cr200060g. Epub 2011 Jun 1. PMID: 21631125.