The role of weak interactions in lignin polymerization
Open accessAbstract
Lignin is the most abundant natural polymer composed by aromatic moieties. Its chemical composition and its abundance have focused efforts to unlock its potential as a source of aromatic compounds for many years. The lack of a proper way for lignin de-polymerization has hampered its success as a natural solution for commodity aromatic chemicals, which is also due to the lack of understanding of the underlying mechanisms of lignin polymerization. A fuller fundamental understanding of polymerization mechanisms could lead to improvements in de-polymerization strategies, and therefore a proper methodology and a predictive theoretical framework are required for such purpose. This work presents a complete computational study on some of the key steps of lignin polymerization mechanisms. Density functional theory (DFT) calculations have been performed to evaluate the most appropriate methodology and to compute the chemical structures and reaction enthalpies for the monolignol dimerization, the simplest key step that controls the polymerization. Quantum theory of atoms in molecules (QTAIM) has been applied to understand the coupling reaction mechanisms, for which the radical species and transition states (TSs) involved have been characterized. The coupling that leads to the formation of the β-O-4 linkage has been theoretically reproduced according to proposed mechanisms, for which weak interactions have been found to play a key role in the arrangement of reactants. The hydrogen bond formed between the oxygen of the phenoxy radical, and the alcohol of the aliphatic chain, together with the interaction between aromatic rings, locates the reactants in a position that favors such β-O-4 linkage. Graphical Abstract QTAIM analysis of the complex between coumaryl and coniferyl alcohols. It emphasizes the importance of weak interactions during the formation of beta-O-4 linkages in the polymerization of lignin.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Most of the research focus has been traditionally placed on the beta-O-4 bond in the lignin structure.
“Moreover, most of the research focus has been traditionally placed on the beta-O-4 bond in the lignin structure (Sanchez-Gonzalez et al., 2017), but other relevant bonds need to be targeted as well.”
From Biorefineries: Achievements and challenges for a bio-based economy (2022) · cites this paper as Sanchez-Gonzalez et al., 2017
Cites
Density-functional thermochemistry. III. The role of exact exchange
Becke, A. D. (1993) · The Journal of Chemical Physics · doi:10.1063/1.464913 · Cited by 103,767 · see citing works
Lee, C., Yang, W., & Parr, R. G. (1988) · Physical Review B · doi:10.1103/physrevb.37.785 · Cited by 100,874 · see citing works
Zhao, Y., & Truhlar, D. G. (2007) · Theoretical Chemistry Accounts · doi:10.1007/s00214-007-0310-x · Cited by 30,407 · see citing works
Intermolecular interactions from a natural bond orbital, donor-acceptor viewpoint
Reed, A. E., Curtiss, L. A., & Weinhold, F. (1988) · Chemical Reviews · doi:10.1021/cr00088a005 · Cited by 17,450 · see citing works
Long-range corrected hybrid density functionals with damped atom–atom dispersion corrections
Chai, J.-D., & Head-Gordon, M. (2008) · Physical Chemistry Chemical Physics · doi:10.1039/b810189b · Cited by 14,648 · see citing works
Bader, R. F. W. (1990) · doi:10.1093/oso/9780198551683.001.0001 · Cited by 12,664 · see citing works
Atoms in molecules : a quantum theory
Bader, R. F. W. (1990) · Clarendon Press eBooks · Cited by 11,749 · see citing works
Revealing Noncovalent Interactions
Johnson, E. R., Keinan, S., Mori‐Sánchez, P., Contreras‐García, J., Cohen, A. J., & Yang, W. (2010) · Journal of the American Chemical Society · doi:10.1021/ja100936w · Cited by 9,597 · see citing works
Boerjan, W., Ralph, J., & Baucher, M. (2003) · Annual Review of Plant Biology · doi:10.1146/annurev.arplant.54.031902.134938 · Cited by 4,504 · see citing works
Wood Chemistry: Fundamentals and Applications
Sjöström, E. (1981) · Cited by 1,902 · see citing works
Cellulose: the structure slowly unravels
O'sullivan, A. C. (1997) · Cellulose · doi:10.1023/a:1018431705579 · Cited by 1,501 · see citing works
Review of current and future softwood kraft lignin process chemistry
Chakar, F. S., & Ragauskas, A. J. (2004) · Industrial Crops and Products · doi:10.1016/j.indcrop.2004.04.016 · Cited by 1,203 · see citing works
The Genetics of Lignin Biosynthesis: Connecting Genotype to Phenotype
Bonawitz, N. D., & Chapple, C. C. S. (2010) · Annual Review of Genetics · doi:10.1146/annurev-genet-102209-163508 · Cited by 773 · see citing works
Young, D. C. (2001) · Wiley eBooks · doi:10.1002/0471220655 · Cited by 670 · see citing works
Zhao, Y., & Truhlar, D. G. (2008) · Theoretical Chemistry Accounts · doi:10.1007/s00214-007-0401-8 · Cited by 560 · see citing works
Can short-range hybrids describe long-range-dependent properties?
Henderson, T. M., Izmaylov, A. F., Scalmani, G., & Scuseria, G. E. (2009) · The Journal of Chemical Physics · doi:10.1063/1.3185673 · Cited by 555 · see citing works
RECENT ADVANCES IN UNDERSTANDING LIGNIN BIOSYNTHESIS
Whetten, R. W., MacKay, J. J., & Sederoff, R. R. (1998) · Annual Review of Plant Physiology and Plant Molecular Biology · doi:10.1146/annurev.arplant.49.1.585 · Cited by 479 · see citing works
Quantification of lignin–carbohydrate linkages with high-resolution NMR spectroscopy
Balakshin, M. Y., Capanema, E. A., Gracz, H. S., Chang, H., & Jameel, H. (2011) · Planta · doi:10.1007/s00425-011-1359-2 · Cited by 453 · see citing works
Computational Study of Bond Dissociation Enthalpies for a Large Range of Native and Modified Lignins
Kim, S., Chmely, S. C., Nimlos, M. R., Bomble, Y. J., Foust, T. D., Paton, R. S., & Beckham, G. T. (2011) · The Journal of Physical Chemistry Letters · doi:10.1021/jz201182w · Cited by 433 · see citing works
Lignin: Its Constitution and Formation from p -Hydroxycinnamyl Alcohol
Freudenberg, K. (1965) · Science · doi:10.1126/science.148.3670.595 · Cited by 402 · see citing works
Lignin and Lignans as Renewable Raw Materials
Calvo‐Flores, F. G., Dobado, J. A., Isac‐García, J., & Martín‐Martínez, F. J. (2015) · Wiley eBooks · doi:10.1002/9781118682784 · Cited by 206 · see citing works
A structural model of softwood lignin
Sakakibara, A. (1980) · Wood Science and Technology · doi:10.1007/bf00584038 · Cited by 205 · see citing works
Beste, A., & Buchanan, A. C. (2009) · The Journal of Organic Chemistry · doi:10.1021/jo9001307 · Cited by 168 · see citing works
Remya, K., & Suresh, C. H. (2013) · Journal of Computational Chemistry · doi:10.1002/jcc.23263 · Cited by 147 · see citing works
Radical Coupling Reactions in Lignin Synthesis: A Density Functional Theory Study
Sangha, A. K., Parks, J. M., Standaert, R. F., Ziebell, A., Davis, M. F., & Smith, J. C. (2012) · The Journal of Physical Chemistry B · doi:10.1021/jp2122449 · Cited by 129 · see citing works
Lignin and Lignans as Renewable Raw Materials: Chemistry, Technology and Applications
Calvo‐Flores, F. G., Dobado, J. A., Isac‐García, J., & Martín‐Martínez, F. J. (2015) · Ghent University Academic Bibliography (Ghent University) · Cited by 119 · see citing works
Density functional theory studies on pyrolysis mechanism of β-O-4 type lignin dimer model compound
Huang, J., Liu, C., Wu, D., Tong, H., & Ren, L. (2014) · Journal of Analytical and Applied Pyrolysis · doi:10.1016/j.jaap.2014.07.007 · Cited by 115 · see citing works
Computational Study of Bond Dissociation Enthalpies for Substituted β‐O‐4 Lignin Model Compounds
Younker, J. M., Beste, A., & Buchanan, A. C. (2011) · ChemPhysChem · doi:10.1002/cphc.201100477 · Cited by 106 · see citing works
Computational study of bond dissociation enthalpies for lignin model compounds: β-5 Arylcoumaran
Younker, J. M., Beste, A., & Buchanan, A. C. (2012) · Chemical Physics Letters · doi:10.1016/j.cplett.2012.07.017 · Cited by 93 · see citing works
Petridis, L., Pingali, S. V., Urban, V. S., Heller, W. T., O’Neill, H., Foston, M. B., Ragauskas, A. J., & Smith, J. C. (2011) · Physical Review E · doi:10.1103/physreve.83.061911 · Cited by 83 · see citing works
Beste, A. (2014) · The Journal of Physical Chemistry A · doi:10.1021/jp410454q · Cited by 82 · see citing works
Carbon···Carbon Weak Interactions
Alkorta, I., Blanco, F., Elguero, J., Dobado, J. A., Ferrer, S. M., & Vidal, I. (2009) · The Journal of Physical Chemistry A · doi:10.1021/jp903016e · Cited by 75 · see citing works
Janesko, B. G. (2014) · Physical Chemistry Chemical Physics · doi:10.1039/c3cp53836b · Cited by 62 · see citing works
A density functional theory study on formation mechanism of CO, CO2 and CH4 in pyrolysis of lignin
Huang, J., Liu, C., Tong, H., Li, W., & Wu, D. (2014) · Computational and Theoretical Chemistry · doi:10.1016/j.comptc.2014.06.009 · Cited by 61 · see citing works
Aoyama, W., Sasaki, S., Matsumura, S., Mitsunaga, T., Hirai, H., Tsutsumi, Y., & Nishida, T. (2002) · Journal of Wood Science · doi:10.1007/bf00766646 · Cited by 58 · see citing works
Macromolecular replication during lignin biosynthesis
Chen, Y., & Sarkanen, S. (2010) · Phytochemistry · doi:10.1016/j.phytochem.2009.11.012 · Cited by 55 · see citing works
A computational study of pyrolysis reactions of lignin model compounds
Elder, T. (2010) · Holzforschung · doi:10.1515/hf.2010.086 · Cited by 52 · see citing works
Kinetic Analysis of the Phenyl-Shift Reaction in β-O-4 Lignin Model Compounds: A Computational Study
Beste, A., & Buchanan, A. C. (2011) · The Journal of Organic Chemistry · doi:10.1021/jo2000385 · Cited by 50 · see citing works
Besombes, S., Robert, D. R., Utille, J. P., Taravel, F. R., & Mazeau, K. (2002) · Journal of Agricultural and Food Chemistry · doi:10.1021/jf0206668 · Cited by 46 · see citing works
Formation of β-O-4 Lignin Models -A Theoretical Study
Durbeej, B., & Eriksson, L. A. (2003) · Holzforschung · doi:10.1515/hf.2003.070 · Cited by 43 · see citing works
Durbeej, B., & Eriksson, L. A. (2003) · Holzforschung · doi:10.1515/hf.2003.024 · Cited by 42 · see citing works
A computational study on thermal decomposition mechanism of β-1 linkage lignin dimer
Huang, J., He, C., Liu, C., Tong, H., Wu, L., & Wu, S. (2014) · Computational and Theoretical Chemistry · doi:10.1016/j.comptc.2014.12.007 · Cited by 42 · see citing works
Kobayashi, T., Taguchi, H., Shigematsu, M., & Tanahashi, M. (2005) · Journal of Wood Science · doi:10.1007/s10086-005-0702-2 · Cited by 41 · see citing works
Setälä, H., Pajunen, A., Rummakko, P., Sipilä, J., & Brunow, G. (1999) · Journal of the Chemical Society Perkin Transactions 1 · doi:10.1039/a808884e · Cited by 39 · see citing works
Evidence for Complex Molecular Architectures for Solvent-Extracted Lignins
Harton, S. E., Pingali, S. V., Nunnery, G. A., Baker, D. A., Walker, S. H., Muddiman, D. C., Koga, T., Rials, T. G., Urban, V. S., & Langan, P. A. (2012) · ACS Macro Letters · doi:10.1021/mz300045e · Cited by 39 · see citing works
Besombes, S., & Mazeau, K. (2004) · Biopolymers · doi:10.1002/bip.10587 · Cited by 34 · see citing works
Beste, A., & Buchanan, A. C. (2013) · The Journal of Physical Chemistry A · doi:10.1021/jp4015004 · Cited by 34 · see citing works
Besombes, S., Utille, J. P., Mazeau, K., Robert, D. R., & Taravel, F. R. (2004) · Magnetic Resonance in Chemistry · doi:10.1002/mrc.1317 · Cited by 29 · see citing works
Spin Distribution in Dehydrogenated Coniferyl Alcohol and Associated Dilignol Radicals
Durbeej, B., & Eriksson, L. A. (2003) · Holzforschung · doi:10.1515/hf.2003.009 · Cited by 22 · see citing works
Besombes, S., Robert, D. R., Utille, J. P., Taravel, F. R., & Mazeau, K. (2003) · Holzforschung · doi:10.1515/hf.2003.040 · Cited by 19 · see citing works
Watts, H. D., Ali, M. M. N., & Kubicki, J. D. (2011) · Physical Chemistry Chemical Physics · doi:10.1039/c1cp21906e · Cited by 17 · see citing works
Relative Binding Affinities of Monolignols to Horseradish Peroxidase
Sangha, A. K., Petridis, L., Cheng, X., & Smith, J. C. (2016) · The Journal of Physical Chemistry B · doi:10.1021/acs.jpcb.6b00789 · Cited by 8 · see citing works
Flagged first, then by citations
2 of the 54 references couldn’t be matched to a known paper.
Cited by
Sorted by citations
Biorefineries: Achievements and challenges for a bio-based economy
Calvo-Flores, F. G., & Martin-Martinez, F. J. (2022) · Frontiers in Chemistry · doi:10.3389/fchem.2022.973417 · Cited by 176 · see citing works
“Moreover, most of the research focus has been traditionally placed on the beta-O-4 bond in the lignin structure (Sanchez-Gonzalez et al., 2017), but other relevant bonds need to be targeted as well.”
BackgroundSustainable lignin to enhance asphalt binder oxidative aging properties and mix properties
Arafat, S., Kumar, N., Wasiuddin, N. M., Owhe, E. O., & Lynam, J. G. (2019) · Journal of Cleaner Production · doi:10.1016/j.jclepro.2019.01.238 · Cited by 170 · see citing works
Understanding Plant Biomass via Computational Modeling
Zhou, S., Jin, K., & Buehler, M. J. (2020) · Advanced Materials · doi:10.1002/adma.202003206 · Cited by 74 · see citing works
Biomass carbon mining to develop nature-inspired materials for a circular economy
Bachs-Herrera, A., York, D., Stephens-Jones, T., Mabbett, I. W., Yeo, J., & Martín‐Martínez, F. J. (2023) · iScience · doi:10.1016/j.isci.2023.106549 · Cited by 27 · see citing works
Thread based microfluidic platform for urinary creatinine analysis
Arroyo, M. J., Erenas, M. M., de Orbe-Payá, I., Cantrell, K., Dobado, J. A., Ballester, P., Blondeau, P., Salinas‐Castillo, A., & Capitán-Vallvey, L. F. (2019) · Sensors and Actuators B Chemical · doi:10.1016/j.snb.2019.127407 · Cited by 24 · see citing works
Kramer, C. A. C., da Silva, Á. R. L., de Lima‐Neto, P., & de Carvalho, L. S. (2021) · Journal of Molecular Structure · doi:10.1016/j.molstruc.2021.131938 · Cited by 17 · see citing works
Kramer, C. A. C., da Silva, Á. R. L., & de Carvalho, L. S. (2020) · Organic & Biomolecular Chemistry · doi:10.1039/d0ob01171a · Cited by 15 · see citing works
Sánchez-González, Á., & Gil, A. (2021) · RSC Advances · doi:10.1039/d0ra07646e · Cited by 16 · see citing works
Types of lignin, properties, and structural characterization techniques
Rumpf, J., Do, X. T., Burger, R., Monakhova, Y. B., & Schulze, M. (2021) · Elsevier eBooks · doi:10.1016/b978-0-12-820303-3.00001-1 · Cited by 15 · see citing works
Levina, E. O., Khrenova, M. G., Astakhov, A. A., & Григорьевич, Ц. В. (2020) · RSC Advances · doi:10.1039/c9ra10649a · Cited by 15 · see citing works
From lignin to single-atom catalysts: advances and perspectives—a review
Meng, Y., Pan, X., Sun, Y., Wu, Z., Jiang, H., & Tan, T. (2026) · Green Chemistry · doi:10.1039/d5gc05967d · Cited by 9 · see citing works
Esteves, T., Ferreira, F. A., Mota, A. T., Sánchez-González, Á., Gil, A., Andrade, K. H. S., Afonso, C. A. M., & Ferreira, F. C. (2022) · ACS Applied Materials & Interfaces · doi:10.1021/acsami.2c02053 · Cited by 9 · see citing works
Stereo-Recognition of Hydrogen Bond and Its Implications for Lignin Biomimetic Synthesis
Zhu, X., Zhang, C., Ma, H., & Lü, F. (2022) · Biomacromolecules · doi:10.1021/acs.biomac.2c00609 · Cited by 7 · see citing works
Heterogeneous and Homogeneous Components in Gas-Phase Pyrolysis of Hydrolytic Lignin
Barekati-Goudarzi, M., Boldor, D., Khachatryan, L., Lynn, B. C., Kalinoski, R. M., & Shi, J. (2020) · ACS Sustainable Chemistry & Engineering · doi:10.1021/acssuschemeng.0c03366 · Cited by 6 · see citing works
Interfacial strategies and bioengineering of lignin-derived strong and tough gels
Gu, Y., Yuan, Y., Zhang, C., Wu, W., Rahman, M. M., Jiang, B., & Jin, Y. (2025) · Renewable and Sustainable Energy Reviews · doi:10.1016/j.rser.2025.116415 · Cited by 5 · see citing works
Weak bonds between molecular tweezers and their guests
Bosquez, M., Cambray, A., Miralrio, A., del Castillo, R.-M., & Salcedo, R. (2017) · Computational and Theoretical Chemistry · doi:10.1016/j.comptc.2017.07.010 · Cited by 5 · see citing works
Organometallic complexes of carbon nanotori
del Castillo, R. M., Miralrio, A., Ríos, C., & Salcedo, R. (2019) · Journal of Molecular Modeling · doi:10.1007/s00894-019-4118-0 · Cited by 4 · see citing works
Zhu, X., Zhang, D., Lu, R., & Lü, F. (2023) · Organic & Biomolecular Chemistry · doi:10.1039/d3ob00275f · Cited by 4 · see citing works
Taboada‐Puig, R., Lu-Chau, T. A., Moreira, M. T., Feijóo, G., Lema, J. M., Fagerstedt, K., Ohra‐aho, T., Liitiä, T., Heikkinen, H. A., Ropponen, J., et al. (2017) · Biotechnology Progress · doi:10.1002/btpr.2562 · Cited by 4 · see citing works
“In natural lignin, the most abundant linkage is b-O-4, whereas the most abundant linkages in DHPs are b-b or b-5.(3,4) Polymerization of lignin precursors to lignin has been shown to be catalyzed by peroxidase/H2O2 in plant cell walls.”
BackgroundThe Role of Noncovalent Interactions in the Infrared Spectra of Lignin Model Compounds: A DFT Study
Rusydi, F., Boli, L. S. P., Adilina, I. B., Cahyanto, W. T., Parker, S. F., & Oemry, F. (2025) · Molecules · doi:10.3390/molecules30244694 · Cited by 2 · see citing works
“The role of π ··· π stacking in lignin polymerization has been elaborated previously by DFT [18] which concluded that hydrogen bonding and π ··· π stacking between two monolignols initiate and lead the formation of the β –”
Multiscale Modeling of Lignocellulosic Biomass
Martín‐Martínez, F. J., Dobado, J. A., Sánchez-González, Á., Barreiro, D. L., & Buehler, M. J. (2020) · Springer eBooks · doi:10.1007/978-3-319-44680-6_87 · Cited by 2 · see citing works
Multiscale Modeling of Lignocellulosic Biomass
Martín‐Martínez, F. J., Dobado, J. A., Sánchez-González, Á., Barreiro, D. L., & Buehler, M. J. (2018) · Springer eBooks · doi:10.1007/978-3-319-50257-1_87-1 · Cited by 2 · see citing works
Lignification-mimetic dehydrogenative diphenoquinone synthesis and electrochemical CO 2 capture
Kim, H., Shinnawy, O., Ulusoy, S., Salazar‐Alvarez, G., Tran, N. T., Cho, H., Sung, C., Kim, S.-S., Koo, B., Jeong, K., et al. (2026) · Green Chemistry · doi:10.1039/d5gc05304h
Mannich reaction with organozinc reagents in continuous flow: experimental and computational studies
Fraile-González, L., Sánchez-González, Á., Fernández-Peña, L., & López, E. (2026) · RSC Advances · doi:10.1039/d6ra01038e
Behavior of the βO4 bond in chlorinated lignin models: a computational theoretical approach
Peixinho, I. M. F., Costa, Y. S., Kramer, C. A. C., & da Silva, Á. R. L. (2026) · Computational and Theoretical Chemistry · doi:10.1016/j.comptc.2026.116101
- Authors
- Sánchez-González, Á., Martín-Martínez, F. J., & Dobado, J. A.
- Affiliations
- Universidad Técnica Particular de Loja (EC)
- Universidad de Granada (ES)
- Venue
- Journal of Molecular Modeling
- Published
- 2017-02-16
- Volume
- 23
- Issue
- 3
- Pages
- 80-80
- ISSN
- 0948-5023 (ISSN-L)
- 1610-2940
- OpenAlex
- W2588178786
- Cited by
- 25
- References
- 54
- Citations by year
- 2026: 4 · 2025: 2 · 2023: 2 · 2022: 3 · 2021: 3 · 2020: 5 · 2019: 3 · 2018: 1 · 2017: 2
- FWCI
- 1.36
- Type
- journal article
- Language
- en
- Open access
- green
- dspace.utpl.edu.ec
- Licence
- Locations
- Journal of Molecular Modeling (publishedVersion)
- PubMed (publishedVersion)
- LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, other-oa)
- DSpace@MIT (Massachusetts Institute of Technology) (submittedVersion, cc-by-nc)
- Springer eBooks
- Funders
- Secretaría de Educación Superior, Ciencia, Tecnología e Innovación
- Topics
- Physical Sciences › Engineering › Biomedical Engineering › Lignin and Wood Chemistry
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Plant-derived Lignans Synthesis and Bioactivity
- Physical Sciences › Engineering › Building and Construction › Wood Treatment and Properties
- Keywords
- lignin polymerization, β-O-4 linkages, weak interaction, hydrogen bonding, coniferyl alcohol, radical coupling, transition state, heat of reaction, quantum theory of atoms in molecules, aromatic monomers
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
