AlphaFold2 and Deep Learning for Elucidating Enzyme Conformational Flexibility and Its Application for Design

Casadevall, G.; Duran, C.; Osuna, S.*JACS Au 20233, 1554–1562.

Estimating conformational heterogeneity of tryptophan synthase with a template-based AlphaFold2 approach 

Casadevall, G.; Duran, C.; Estévez-Gay, M.; Osuna, S.* Prot. Sci. 2022, 31, e4426.

In Silico Identification and Experimental Validation of Distal Activity-Enhancing Mutations in Tryptophan Synthase

Maria-Solano, M.A.*; Kinateder, T.; Iglesias-Fernández, J.; Sterner, R.*; Osuna, S*, ACS Catal. 202111, 13733-13743.

The challenge of predicting distal active site mutations in computational enzyme design

Osuna, S.* WIREs Comput Mol Sci2020, e1502.

Deciphering the Allosterically Driven Conformational Ensemble in Tryptophan Synthase Evolution

Maria-Solano, M. A; Iglesias-Fernández, J.*; Osuna, S.*J. Am. Chem. Soc. 2019141, 33, 13049-13056.

Efficient reductive desymmetrization of bulky 1,3-cyclodiketones enabled by structure-guided directed evolution of a carbonyl reductase

Chen, X.; Zhang, H.; Maria-Solano, M. A.; Liu, W.; Li, J.; Feng, J.; Liu, X.; Osuna, S.*; Guo, R. T.; Wu, Q.*; Zhu, D.*, Ma, Y. Nature Catal. 20192, 931-941. 


103. Peccati,F.; Noey, E. L.; Houk, K. N.*; Osuna, S.*; Jiménez-Osés, G.* Interplay Between Substrate Polarity and Protein Dynamics in Evolved Kemp Eliminases, ChemCatChem, 2024, e202400444 (doi: 10.1002/cctc.202400444)

102. Duran, C.; Casadevall, G.; Osuna, S.* Harnessing Conformational Dynamics in Enzyme Catalysis to achieve Nature-like catalytic efficiencies: The Shortest Path Map tool for computational enzyme design, Faraday Discuss. 2024, ASAP (doi: 10.1039/D3FD00156C)

101. Casadevall, G.; Casadevall, J.; Duran, C.; Osuna, S.* The shortest path method (SPM) webserver for computational enzyme design, Protein Eng. Des. Sel., 2024, gzae005 (doi: 10.1093/protein/gzae005).

100. Ludwig, J.; Curado-Carballada, C.; Hammer, S. C.; Schneider, A.; Diether, S.; Kress, N.; Ruiz-Barragán, S.; Osuna, S.*; Hauer, B.* Controlling Monoterpene Isomerization by Guiding Challenging Carbocation Rearrangement Reactions in Engineered Squalene‑Hopene Cyclases, Angew. Chem. Int. Ed. 2024, e202318913. (doi: 10.1002/anie.202318913).

99. Castelli, M.; Marchetti, F.; Osuna, S.; Oliveira, A. S. F.; Mulholland, A. J.; Serapian*, S. A.; Colombo, G* Decrypting Allostery in Membrane-Bound K-Ras4B Using Complementary In Silico Approaches Based on Unbiased Molecular Dynamics Simulations, J. Am. Chem. Soc2024146, 901–919. (doi: 10.1021/jacs.3c11396).

98. Menendez, J. A.*; Cuyàs, E.; Encinar, J. A.; Steen, T. V.; Verdura, S.; Llop-Hernández, A.; López, J.;  Serrano-Hervás, E.; Osuna, S.; Martin-Castillo, B.; Lupu, R.* The Fatty Acid Synthase (FASN) signalome: A molecular guide for precision oncology, Mol. Oncol. 2024. (doi: 10.1002/1878-0261.13582).

97. Busch, M. R.; Drexler, L.; Mahato, D.; Hiefinger, C.; Osuna, S.*; Sterner, R.* Retracing the Rapid Evolution of an Herbicide-Degrading Enzyme by Protein Engineering, ACS Catal., 202313, 15558-15571. (doi: 10.1021/acscatal.3c04010).

96. Palone, A.; Casadevall, G.; Ruiz-Barragan, S.; Call, A.; Osuna, S.*; Bietti, M.*; Costas, M.* C–H Bonds as Functional Groups: Simultaneous Generation of Multiple Stereocenters by Enantioselective Hydroxylation at Unactivated Tertiary C–H Bonds, J. Am. Chem. Soc. 2023, 145, 15742–15753. (doi: 10.1021/jacs.2c10148).

95. Casadevall, G.; Duran, C.; Osuna, S.AlphaFold2 and Deep Learning for Elucidating Enzyme Conformational Flexibility and Its Application for Design, JACS Au 202331554–1562. (doi: 10.1021/jacsau.3c00188).

94. Schneider, A.Curado, C.Lystbaek, T. B.Osuna, S.*Hauer, B.* Harnessing the Structure and Dynamics of the Squalene‐Hopene Cyclase for (−)‐Ambroxide Production, Angew. Chem. Int. Ed. 2023, 62, e202301607. (doi: 10.1002/anie.202301607).

93. Shehata, M.;  Ünlü, A.; Iglesias-Fernández, J.;  Osuna, S.; Sezerman, O. U.; Timucin, E. Brave new surfactant world revisited by thermoalkalophilic lipases: computational insights into the role of SDS as a substrate analog, Phys. Chem. Chem. Phys. 202325, 2234-2247. (doi: 10.1039/d2cp05093e).

92. Casadevall, G.; Duran, C.; Estévez-Gay, M.; Osuna, S.* Estimating conformational heterogeneity of tryptophan synthase with a template-based AlphaFold2 approach, Prot. Sci. 2022, 31, e4426 (special issue dedicated to Prof. D. Tawfik). (doi: 10.1002/pro.4426).

91. Codony, S.; Entrena, J. M.; Calvó-Tusell, C.; Jora, B.; González Cano, R.; Osuna, S.; Corpas, R.; Morisseau, C.; Perez, B.; Barniol-Xicota, M.; Griñán-Ferré, C.; Pérez, C.; Rodríguez-Franco, M. I.; Martinez, A. L.; Loza, M.; Pallàs, M.; Verhelst, S.; Sanfeliu, C.; Feixas, F.; Hammock, B.; Brea, J.; Cobos, E.; Vazquez, S.* Synthesis, in vitro profiling and in vivo evaluation of benzohomoadamantane-based ureas for visceral pain: a new indication for soluble epoxide hydrolase inhibitors, J. Med. Chem. 202265, 13660-13680. (doi: 10.1021/acs.jmedchem.2c00515).

90. Calvó-Tusell, C.; Maria-Solano, M.*; Osuna, S.*; Feixas, F.* Time evolution of the millisecond Allosteric Activation of Imidazole Glycerol Phosphate Synthase, J. Am. Chem. Soc. 2022, 144, 7146-7159. (doi: 10.1021/jacs.1c12629).

89. Codony, S.; Pont, C.; Griñán-Ferré, C.; Di Pede-Mattatelli, A.; Calvó-Tusell, C.; Feixas, F.; Osuna, S.; Jarné-Ferrer, J.; Naldi, M.; Bartolini, M.; Loza, M. I.; Brea, J.; Pérez, B.; Bartra, C.; Sanfeliu, C.; Juárez-Jiménez, J.; Morisseau, C.; Hammock, B. D.; Pallàs, M.; Vázquez, S.*; Muñoz-Torrero, D.* Discovery and In Vivo Proof of Concept of a Highly Potent Dual Inhibitor of Soluble Epoxide Hydrolase and Acetylcholinesterase for the Treatment of Alzheimer’s Disease. J. Med. Chem. 2022654909–4925. (doi: 10.1021/acs.jmedchem.1c02150).

88. Maria-Solano, M. A.*; Kinateder, T.; Iglesias-Fernández, J.; Sterner, R.*; Osuna, S.* In Silico Identification and Experimental Validation of Distal Activity-Enhancing Mutations in Tryptophan Synthase. ACS Catal. 202111, 13733-13743. (doi:10.1021/acscatal.1c03950).

87. Bell, E. L.; Finnigan, W.; France, S. P.; Green, A. P.; Hayes, M. A.; Hepworth, L. J.; Lovelock, S. L.; Niikura, H.; Osuna, S.; Romero, E., Ryan, K. S.; Turner, N. J.; Flitsch, S. L.* Biocatalysis. Nat. Rev. Methods Primers 20211, 46. (doi:10.1038/s43586-021-00044-z).

86. Floor, M.*; Li, K.; Estévez-Gay, M.; Agulló, L.; Muñoz-Torres, P.M.; Hwang, J.K.; Osuna, S.; Villà-Freixa, J. SBMOpenMM: A Builder of Structure-Based Models for OpenMM. J. Chem. Inf. Model. 202161, 3166-3171. (doi: 10.1021/acs.jcim.1c00122).

85. Codony, S.; Calvó-Tusell, C.; Valverde, E.; Osuna, S.; Morisseau, C.; Loza, M.I.; Brea, J.; Pérez, C.; Rodríguez-Franco, M.I.; Pizarro-Delgado, J., et al. From the Design to the In Vivo Evaluation of Benzohomoadamantane-Derived Soluble Epoxide Hydrolase Inhibitors for the Treatment of Acute Pancreatitis. J. Med. Chem. 202164, 5429-5446. (doi:10.1021/acs.jmedchem.0c01601).

84. Acevedo-Rocha, C.; Li, A.; D’Amore, L.; Hoebenreich, S.; Sanchis, J.; Lubrano, P.; Ferla, M. P.; Garcia-Borràs, M.; Osuna, S.*; Reetz, M.*; Pervasive cooperative mutational effects on multiple catalytic enzyme traits emerge via long-range conformational dynamics, Nature Commun. 202112, 1621. (doi: 10.1038/s41467-021-21833-w).

83. Wessel, J.; Petrillo, G.; Estevez‐Gay, M.; Bosch, S.; Seeger, M.; Dijkman, W. P.; Iglesias‐Fernández, J.; Hidalgo, A.; Uson, I.; Osuna, S.; Schallmey, A.* Insights into the molecular determinants of thermal stability in halohydrin dehalogenase HheD2. The FEBS Journal 2021, 288, 4683-4701. (doi:

82. Estévez-Gay, M.; Iglesias Fernández, J.*; Osuna, S.* Conformational landscapes of Halohydrin dehalogenases and their accessible active site tunnels, Catalysts 202010, 1403. (doi: 10.3390/catal10121403).

81. Osuna, S.* The challenge of predicting distal active site mutations in computational enzyme design, WIREs Comput Mol Sci2020, 11, e1502. (doi: 10.1002/wcms.1502).

80. Cuetos, A.; Iglesias-Fernández, J.; Danesh-Azari, H.-R.; Zukic, E.; Dowle, A.; Osuna, S.; Grogan, G.* Mutational Analysis of Linalool Dehydratase Isomerase Suggests That Alcohol and Alkene Transformations Are Catalyzed Using Noncovalent MechanismsACS Catalysis 2020 10, 11136-11146. (doi: 10.1021/acscatal.0c02958).

79. Wang, L., Marciello, M., Estévez-Gay, M., Rodriguez, P..E., Morato, Y..L., Iglesias-Fernández, J., Huang, X., Osuna, S., Filice, M.* and Sanchez, S.* Enzyme Conformation Influences the Performance of Lipase‐powered Nanomotors. Angew. Chem. Int. Ed. 202059, 21080-21087. (doi: 10.1002/anie.202008339).

78. Codony, S.; Pujol, E.; Pizarro-Delgado, J.; Feixas, F.; Valverde, E.; Loza, M. I.; Brea, J. M.; Sáez, E.; Oyarzabal, J.; Pineda-Lucena, A.; Pérez, B.; Perez, C.; Rodríguez-Franco, M. I.; Leiva, R.; Osuna, S.; Morisseau, C.; Hammock, B. D.; Vázquez-Carrera, M.; Vazquez, S.* 2-Oxaadamant-1-yl ureas as soluble epoxide hydrolase inhibitors: in vivo evaluation in a murine model of acute pancreatitis, J. Med. Chem. 202063, 9237-9257. (doi: 10.1021/acs.jmedchem.0c00310).

77. Semivrazhskaya, O; Aroua, S.; Yulikov, M.; Romero-Rivera, A.; Stevenson, S.;  Garcia-Borràs, M.; Osuna, S.*; Yamakoshi, Y.* Regioselective Synthesis and Characterization of Tris- and Tetra-Prato Adducts of M3N@C80 (M = Y, Gd), J. Am. Chem. Soc. 2020142, 12954-12965. (doi: 10.1021/jacs.9b13768).

76. Li, A., Acevedo‐Rocha, C.G., D’Amore, L., Chen, J., Peng, Y., Garcia‐Borràs, M., Gao, C., Zhu, J., Rickerby, H., Osuna, S.*, Zhou, J.* and Reetz, M.T.* Regio‐ and Stereoselective Steroid Hydroxylation at C7 by Cytochrome P450 Monooxygenase Mutants. Angew. Chem. Int. Ed. 202059, 12499-12505. (doi: 10.1002/anie.202003139).

75. Calzadiaz-Ramirez, L.; Calvó-Tusell, C.; Stoffel, G. M. M.; Lindner, S.; Osuna, S.; Erb, T. E.; Garcia-Borràs, M.*; Bar-Evene, A.*; Acevedo-Rocha, C. G.* In Vivo Selection for Formate Dehydrogenases with High Efficiency and Specificity toward NADP+,  ACS Catal. 2020, 10, 7512-7525. (doi: 10.1021/acscatal.0c01487).

74. Liutkus, M.; López-Andarias, A.; Mejías, S. H.; López-Andarias, J.; Gil-Carton, D.; Feixas, F.; Osuna, S.; Matsuda, W.; Sakurai, T.; Seki, S.; Atienza, C.*; Martín, N.*; Cortajarena, A. L.* Protein-directed crystalline 2D fullerene assemblies, Nanoscale 202012, 3614-3622. (doi: 10.1039/C9NR07083D).

73. Castro Aguilera, A. C.; Romero-Rivera, A.; Osuna, S.; Houk, K. N.; Swart, M.* Computational NMR spectra of o-benzyne and stable guests and their hemicarceplexes, Chem. Eur. J. 2020, 26, 2626-2634. (doi: 10.1002/chem.201904756).

72. Chen, X.; Zhang, H.; Maria-Solano, M. A.; Liu, W.; Li, J.; Feng, J.; Liu, X.; Osuna, S.*; Guo, R. T.; Wu, Q.*; Zhu, D.*, Ma, Y. Efficient reductive desymmetrization of bulky 1,3-cyclodiketones enabled by structure-guided directed evolution of a carbonyl reductase, Nature Catal. 20192, 931-941. (doi: 10.1038/s41929-019-0347-y).

71. Maria-Solano, M. A.; Iglesias-Fernández, J.*; Osuna, S.* Deciphering the Allosterically Driven Conformational Ensemble in Tryptophan Synthase Evolution, J. Am. Chem. Soc. 2019141, 33, 13049-13056. (doi: 10.1021/jacs.9b03646).

70. Arqué, X.; Romero-Rivera, A.; Feixas, F.; Patiño, T*.; Osuna, S*., Sánchez, S.* Intrinsic enzymatic properties modulate the self-propulsion of micromotors, Nature Commun. 201910, 2826. (doi: 10.1038/s41467-019-10726-8).

69. Call, A.; Casadevall, C.; Romero-Rivera, A.; Martin-Diaconescu, V.; Sommer, D. J.; Osuna, S.; Ghirlanda, G.*; Lloret-Fillol, J.* Improved Electro- And Photocatalytic Water Reduction by Confined Cobalt Catalysts in Streptavidin, ACS Catalysis 20199, 5837-5846. (doi: 10.1021/acscatal.8b04981).

68. Semivrazhskaya, O.; Romero-Rivera, A.; Aroua, S.; Troyanov, S. I.; Garcia-Borràs, M.; Stevenson, S.; Osuna, S.*; Yamakoshi, Y.* Structures of Gd3N@C80Prato Bis-Adducts: Crystal Structure, Thermal Isomerization, and Computational Study, J. Am. Chem. Soc. 2019, 141, 28, 10988-10993. (doi: 10.1021/jacs.9b05603).

67. Liosi, K.; Romero-Rivera, A.; Semivrazhskaya, O.; Caniglia, C. D.; Garcia-Borràs, M.; Trapp, N.; Osuna, S.*; Yamakoshi, Y.* Site-Selectivity of Prato Additions to C70: Experimental and Theoretical Studies of a New Thermodynamic Product at the dd-[5,6]-Junction, Org. Lett. 2019, 21, 5162-5166. (doi: 10.1021/acs.orglett.9b01756).

66. Curado-Carvallada, C.; Feixas, F*.; Osuna, S.* Molecular Dynamics Simulations on Aspergillus niger Monoamine Oxidase: Conformational Dynamics and Inter‐monomer Communication Essential for Its Efficient Catalysis, Adv. Synth. Catal. 2019361, 2718-2726. (doi: 10.1002/adsc.201900158).

65. Tomás-Loba, A.; Manieri, E.; González-Terán, B.; Mora, A:; Leiva-Vega, L.; Santamans, A. M.; Romero-Becerra, R.; Rodríguez, E.; Pintor-Chocano, A.; Feixas, F.; López, J. A.; Caballero, B.; Trakala, M.; Blanco, O.; Torres, J. L.; Hernández-Cosido, L.; Montalvo-Romeral, V.; Matesanz, N.; Roche-Molina, M.; Bernal, J. A:; Mischo, H.; León, M.; Caballero, A.; Miranda-Saavedra, D.; Ruiz-Cabello, J.; Nevzorova, Y. A.; Cubero, F. J.; Bravo, J.; Vázquez, J.; Malumbres, M.; Marcos, M.; Osuna, S.; Sabio, G.* p38 gamma is essential for cell cycle progression and liver tumourigenesis, Nature 2019568, 557-560. (doi: 10.1038/s41586-019-1112-8).

64. Curado-Carvallada, C.; Feixas, F.; Iglesias-Fernández, J.; Osuna, S.* Hidden conformations in Aspergillus niger Monoamine oxidase are key for catalytic efficiency, Angew. Chem. Int. Ed. 201958, 3097-3101. (doi: 10.1002/anie.201812532).

63. Maria-Solano, M. A.; Serrano-Hervás, E.; Romero-Rivera, A.; Iglesias-Fernández, J.; Osuna, S.* Role of conformational dynamics for the evolution of novel enzyme function, Chem. Commun. 201854, 6622-6634. (doi: 10.1039/C8CC02426J).

62. Serrano-Hervás, E.; Casadevall, G.; Garcia-Borràs, M.; Feixas, F.*; Osuna, S.* Epoxide hydrolase conformational heterogeneity for the resolution of bulky pharmacologically-relevant epoxide substrates, Chem. Eur. J. 201824, 12254-12258. (doi: 10.1002/chem.201801068).

61. Romero-Rivera, A.; Iglesias-Fernández, J.*; Osuna, S.* Exploring the conversion of a D-sialic acid aldolase into a L-KDO aldolase, Eur. J. Org. Chem. 2018, 2603-2608. VIP PAPER. (doi: 10.1002/ejoc.201800103).

60. López-Andarias, J.; H. Mejías, S.; Sakurai, T.; Matsuda, W.; Seki, S.; Feixas, F.; Osuna, S.; Atienza, C.*; Martín, N.*; Cortajarena, A. L.* Toward bioelectronic nanomaterials: photoconductivity in protein-porphyrin hybrids wrapped around SWCNT, Adv. Funct. Mat. 201828, 1704031. (doi: 10.1002/adfm.201704031).

59. Romero-Rivera, A.; Garcia-Borràs, M.;* Osuna, S.* The role of conformational dynamics in the evolution of retro-aldolase activity, ACS Catalysis 20177, 8524-8532. (doi: 10.1021/acscatal.7b02954).

58. Serrano-Hervás, E.; Garcia-Borràs, M.*; Osuna, S*. Exploring the origins of selectivity in soluble Epoxide Hydrolase from Bacillus megaterium, Org. Biomol. Chem. 201715, 8827 – 8835. (doi: 10.1039/C7OB01847A).

57. Vidal, S.; Izquierdo, M.; Alom, S.; Garcia-Borràs, M.; Filippone, S.; Osuna, S.; Solà, M.*; Whitby, R. J.*; Martín, N.* Effect of incarcerated HF on the exohedral chemical reactivity of HF@C60, Chem. Commun.201753, 10993-10996. (doi: 10.1039/C7CC05987F). 

56. Li, G.; Maria-Solano, M. A.; Romero-Rivera, A.; Osuna, S.*; Reetz, M.* Inducing High Activity of a Thermophilic Enzyme At Ambient Temperature by Directed Evolution, Chem. Commun. 201753, 9454- 9457. (doi: 10.1039/C7CC05377K).

55. Garcia-Borràs, M.*; Luis, J. M.; Solà, M.*; Osuna, S.* The Key Role of aromaticity in the structure and reactivity of C60 and endohedral metallofullerenes,‎ Inorg. Chim. Acta 2017, 468, 38-48. Special Issue dedicated to Prof. Echegoyen. (doi: 10.1016/j.ica.2017.07.044).

54. Maria-Solano, M. A.; Romero-Rivera, A.; Osuna, S.* Exploring the reversal of enantioselectivity on a Zinc-dependent Alcohol Dehydrogenase, Org. Biomol. Chem. 201715, 4122–4129. (doi: 10.1039/C7OB00482F).

53. Garcia-Borràs, M.*; Osuna, S.; Luis, J. M.; Solà, M. Rationalizing the Relative Abundances of Trimetallic Nitride Template-based Endohedral Metallofullerenes from Aromaticity Measures,  Chem. Commun. 201753, 4140–4143. (doi: 10.1039/C7CC01750B).

52. Romero-Rivera, A.; Garcia-Borràs, M.; Osuna, S.* Computational tools for the evaluation of laboratory-engineered biocatalysts, Chem. Commun. 2017, 53, 284-297. (doi: 10.1039/C6CC06055B).

51. Li, Y.; Osuna, S.; Garcia-Borràs, M.; Qi, X.; Liu, S.; Houk, K. N.*; Lan, Y.* Reactivity of Single-Walled Carbon Nanotubes in the Diels–Alder Cycloaddition Reaction: Distortion–Interaction Analysis along the Reaction Pathway, Chem. Eur. J. 201622, 12819-12824. (doi: 10.1002/chem.201601799).

50. Martínez, J. P.; Garcia-Borràs, M.; Osuna, S.; Poater, J.; Bickelhaupt, F. M.*; Solà, M.* Reaction Mechanism and Regioselectivity of the Bingel-Hirsch Addition of Dimethyl Bromomalonate to La@C2v-C82, Chem. Eur. J. 201622, 5953-5962. (doi: 10.1002/chem.201504668).

49. Garcia-Borràs, M.; Cerón, M. R.; Osuna, S.*; Izquierdo, M.; Luis, J. M.*; Echegoyen, L.*; Solà, M.* The Regioselectivity of Bingel-Hirsch Cycloadditions on IPR Endohedral Metallofullerenes, Angew. Chem. Int. Ed. 2016, 55, 2374-2377. (doi: 10.1002/anie.201509057).

48. Martínez, J. P.; Langa, F.; Bickelhaupt, F. M.; Osuna, S.*; Solà, M.* (4+2) and (2+2) Cycloadditions of Benzyne to C60 and Zig-Zag Single-Walled Carbon Nanotubes: The Effect of Curvature, J. Phys. Chem. C 2016120, 1716-1726. (doi: 10.1021/acs.jpcc.5b11499).

47. Noey, E. L.; Tibrewal, N.; Jiménez-Osés, G.; Osuna, S.; Park, J.; Bond, C.; Cascio, D.; Liang, J.; Zhang, X.*; Huisman, G.*; Tang, Y.*; Houk, K. N.* Origins of Stereoselectivity in Evolved Ketoredutases, Proc. Natl. Acad. Sci. USA 2015112, E7065-E7072. (doi: 10.1073/pnas.1507910112).

46. Cerón, M. R.; Izquierdo, M.; Garcia-Borràs, M.; Lee, S. S.; Stevenson, S.; Osuna, S.*; Echegoyen, L.* Bis-1,3-Dipolar Cycloadditions on Endohedral Fullerenes M3N@Ih-C80 (M = Sc, Lu): Remarkable Endohedral-Cluster Regiochemical Control, J. Am. Chem. Soc. 2015137, 11775–11782. (doi: 10.1021/jacs.5b07207).

45. Osuna, S; Jiménez-Osés, G.; Noey, L.; Houk, K. N.* Molecular Dynamics Explorations of Active Site Structure in Designed and Evolved Enzymes, Acc. Chem. Res. 2015, 48, 1080-1089. (doi: 10.1021/ar500452q).

44. Maroto, E. E.; Mateos, J.; Garcia-Borràs, M.; Osuna, S.*; Filippone,S.*; Herranz, M. A.; Murata, Y.; Solà, M.*; Martín, N.* Enantiospecific cis-trans Isomerization in Chiral Fulleropyrrolidines: H-Bonding assistance in the carbanion stabilization in H2O@C60 J. Am. Chem. Soc. 2015137, 1190-1197. (doi: 10.1021/ja5108854).

43. Martínez, J. P.; Osuna, S.; Solà, M.*; Voityuk, A. Extent of charge separation and exciton delocalization for electronically excited states in a triphenylamine C60 donor-acceptor conjugate: a combined molecular dynamics and TD-DFT study, Theor. Chem. Acc. 2015, 134, 1. (doi: 10.1007/s00214-015-1614-x).

42. Aroua, S.; Garcia-Borràs, M.; Bölter, M.; Osuna, S.*; Yamakoshi, Y.* Endohedral Metal-induced Regioselective Formation of Bis- Prato Adduct of Y3N@Ih-C80 and Gd3N@Ih-C80 J. Am. Chem. Soc. 2015, 137, 58–61. (doi: 10.1021/ja511008z).

41. Beltran-Alvarez, P.*; Feixas, F.;† Osuna, S.;† Díaz-Hernández, R.; Brugada, R.*; Pagans, S.* Interplay between R513 methylation and S516 phosphorylation of the cardiac voltage-gated sodium channel, Amino Acids 2015, 47, 429-434. (†: the authors have equally contributed). (doi: 10.1007/s00726-014-1890-0).

40. García-Simón,C.; Garcia-Borràs, M.; Gómez, L.; Parella, T.; Osuna, S.; Juanhuix, J.; Imaz, I.; Maspoch, D.; Costas, M.*; Ribas, X.* Sponge-like molecular cage for purification of fullerenes, Nature Commun2014, 5,  5557. (doi: 10.1038/ncomms6557).

39. Aroua, S.; Garcia-Borràs, M.; Osuna, S.*; Yamakoshi, Y.* Essential Factors for Control of the Equilibrium in the Reversible Rearrangement of M3N@Ih-C80, Chem. Eur. J. 2014, 20, 14032-14039. (doi: 10.1002/chem.201403743).

38. Cao, Y.; Liang, Y.; Zhang, L.; Osuna, S.; Hoyt, A.-L. M.; Briseno, A*. L.; Houk, K. N.* Why bistetracenes are much less reactive than pentacenes in Diels-Alder reactions with fullerenes, J. Am. Chem. Soc. 2014, 136, 10743-10751. (doi: 10.1021/ja505240e).

37. Garcia-Borràs, M.; Osuna, S.*; Luis, J. M.*; Swart, M.; Solà, M.* The role of aromaticity in the molecular structure and reactivity of (endohedral metallo)fullerenes,  Chem. Soc. Rev. 2014, 43, 5089-5105. (doi: 10.1039/C4CS00040D).

36. Jiménez-Osés, G.†; Osuna, S.†; Gao, X.†; Sawaya, M. R.; Gilson, L.; Collier, S. J.; Huisman, G. H.*; Yeates, T. O.*; Tang, Y.*; Houk, K. N.* The Role of Distant Mutations and Allosteric Regulation on Active Site Dynamics and Catalysis, Nature Chem. Biol. 2014, 10, 431-436. (†: The authors have equally contributed to the work). (doi: 10.1038/nchembio.1503).

35. Parker, M. F. L.; Osuna, S.; Bollot, G.; Vaddypally, S.; Zdilla, M. J.; Houk, K. N.; Schafmeister, C. E.* Acceleration of an Aromatic Claisen Rearrangement via a Designed Spiroligozyme Catalyst that Mimics the Ketosteroid Isomerase Catalytic Dyad, J. Am. Chem. Soc. 2014, 136, 3817-3827. (doi: 10.1021/ja409214c).

34. Cao, Y.; Osuna, S.; Liang, Y.; Haddon, R.; Houk, K. N.* Diels-Alder Reactions of Graphene: Computational Predictions of Products and Sites of Reaction, J. Am. Chem. Soc. 2013, 135, 17643–17649. (doi: 10.1021/ja410225u).

33. Osuna, S.*; Dermenci, A.; Miller, S. J.; Houk, K. N.* The Roles of Counter-ion and Water in a Stereoselective Cysteine-Catalyzed Rauhut-Currier Reaction: A Challenge for Computational Chemistry, Chem. Eur. J. 2013, 19, 14245-14253. (doi: 10.1002/chem.201300745).

32. Garcia-Borràs, M.; Osuna, S.; Luis, J. M.*; Swart, M.*; Solà, M.* A Complete Guide on the Influence of Metal Clusters in the Diels-Alder Regioselectivity of Ih-C80 Endohedral Metallofullerenes, Chem. Eur. J. 2013, 19, 14931-14940. (doi: 10.1002/chem.201302202).

31. Garcia-Borràs, M.; Osuna, S.; Swart, M.; Luis, J.M.; Solà, M.* Aromaticity as Driving Force for the Stability of non-IPR Endohedral Metallofullerene Bingel-Hirsch Adducts, Chem. Commun. 2013, 49, 8767-8769. (doi: 10.1039/C3CC44505D).

30. Fang, L.; Liu, P.; Sveinbjornsson,B. R.; Atahan-Evrenk, S.; Vandewal, K.; Osuna, S.; Jiménez-Osés, G.; Shrestha, S.; Giri, G.; Wei, P.; Salleo, A.; Aspuru-Guzik, A.; Grubbs, R. H.; Houk, K. N.; Bao, Z.* Confined Organization of Fullerene Units Along High Polymer Chains, J. Mater. Chem. C 2013, 1, 5747-5755. (doi: 10.1039/C3TC31158A).

29. Garcia-Borràs, M.; Osuna, S.; Swart, M.; Luis, J. M.*; Solà, M.* Maximum Aromaticity as a Guiding Principle for the Most Suitable Hosting Cages in Endohedral Metallofullerenes, Angew. Chem. Int. Ed. 2013, 52, 9275-9278. (doi: 10.1002/anie.201303636)

28. Bian, S.; Scott, A. M.; Cao, Y.; Liang, Y.; Osuna, S.; Houk, K. N.*; Braunschweig, A. B.* Covalently Patterned Graphene Surfaces by a Force-Accelerated Diels-Alder Reaction, J. Am. Chem. Soc. 2013, 135, 9240-9243. (doi: 10.1021/ja4042077).

27. Wang, H.; Mei, J.; Liu, P.; Schmidt, K.; Jiménez-Osés, G.; Osuna, S.; Fang, L.;Tassone, C. J.; Zoombelt, A. P.; Sokolov, A. N.; Houk, K. N.; Toney, M. F.; Bao, Z.* Scalable and Selective Dispersion of Semiconducting Arc-Discharged Carbon Nanotubes by Dithiafulvalene/Thiophene Copolymers for Thin Film Transistors, ACS nano 2013, 7, 2659-2668. (doi: 10.1021/nn4000435).

26. Osuna, S.; Kim, S.; Bollot, G.; Houk, K. N.* Aromatic Claisen Rearrangements of O-prenylated Tyrosine and Model Prenyl Aryl Ethers: Computational Study of the Role of Water on Acceleration of Claisen rearrangements, Eur. J. Org. Chem. 2013, 2823-2831. (doi: 10.1002/ejoc.201201738).

25. Garcia-Borràs, M.; Osuna, S.; Swart, M.; Luis, J. M.; Solà, M.* Electrochemical Control of the Regioselectivity in the Exohedral Functionalization of C60: the Role of Aromaticity, Chem. Commun. 2013, 49, 1220-1222. (doi: 10.1039/C2CC38390J).

24. García-Simón, C.; Garcia-Borràs, M.; Gómez, L.; Garcia-Bosch, I.; Osuna, S.; Swart, M.; Luis, J. M.; Rovira, C.; Almeida, M.; Imaz, I.; Maspoch, D.; Costas, M.*; Ribas, X.* Self-Assembled Tetragonal Prismatic Molecular Cage Highly Selective for Anionic π Guests, Chem. Eur. J. 2013, 19, 1445–1456. (doi: 10.1002/chem.201203376).

23. Osuna, S.; Valencia, R.; Rodríguez-Fortea, A.*; Swart, M.*; Solà, M.*; Poblet, J. M.* Full Exploration of the Diels–Alder Cycloaddition on Metallofullerenes M3N@C80 (M=Sc, Lu, Gd): The D5h versus Ih Isomer and the Influence of the Metal Cluster, Chem. Eur. J. 2012, 18, 8944–8956. (doi: 10.1002/chem.201200940).

22. Garcia-Borràs, M.; Osuna, S.; Luis, J. M.*; Swart, M.*; Solà, M. The Exohedral Diels–Alder Reactivity of the Titanium Carbide Endohedral Metallofullerene Ti2C2@D3h-C78: Comparison with D3h-C78 and M3N@D3h-C78 (M=Sc and Y) Reactivity, Chem. Eur. J. 2012, 18, 7141–7154. (doi: 10.1002/chem.201103701).

21. Garcia-Borràs, M.; Romero-Rivera, A.; Osuna, S.; Luis, J. M.*; Swart, M.*; Solà, M.* The Frozen Cage Model: A Computationally Low-Cost Tool for Predicting the Exohedral Regioselectivity of Cycloaddition Reactions Involving Endohedral Metallofullerenes, J. Chem. Theory Comput. 2012, 8, 1671–1683. (doi: 10.1021/ct300044x).

20. Osuna, S.; Rodríguez-Fortea, A.; Poblet, J. M.; Solà, M.*; Swart, M.* Product Formation in the Prato Reaction on Sc3N@D5h-C80: Preference for [5,6]-bonds, and not Pyracylenic Bonds, Chem. Commun. 2012, 48, 2486-2488. (doi: 10.1039/C2CC17210K).

19. Osuna, S.; Swart, M*; Solà, M.* Dispersion Corrections Are Essential for the Study of Chemical Reactivity in Fullerenes, J. Phys. Chem. A 2011, 115, 3491-3496. (doi: 10.1021/jp1091575).

18. Osuna, S.; Swart, M.*; Solà, M.* The Reactivity of Endohedral Fullerenes. What Can Be Learnt from Computational Studies? Phys. Chem. Chem. Phys.2011, 13, 3585-3603. (doi: 10.1039/C0CP01594F).

17. Osuna, S.; Torrent-Sucarrat, M.; Solà, M.; Geerlings, P.; Ewels, C. P.*; Van Lier, G.* Reaction Mechanisms for Graphene and Carbon Nanotube Fluorination, J. Phys. Chem. C 2010, 114, 3340–3345. (doi: 10.1021/jp908887n).

16. Osuna, S.; Swart, M.*; Solà, M., On the Mechanism of the Superoxide Dismutation Involving Fullerene Derivatives. Chem. Eur. J. 2010, 16, 3207-3214. (doi: 10.1002/chem.200902728).

15. Dachs, A.; Osuna, S.; Roglans, A.; Solà, M. A Density Functional Theory Study of the [2+2+2] Cyclotrimerization of Acetylene Catalyzed by the Wilkinson’s Catalyst, RhCl3(PPh3)3. The effect of replacing PPh3 for PH3, Organometallics 2010, 29, 562-569.

14. Izquierdo, M.; Osuna, S.; Filippone, S.; Martín-Domenech, A. ; Solà, M.*; Martín, N.* On the Regioselective Intramolecular Nucleophilic Addition of Thiols to C60. Eur. J. Org. Chem. 2009, 6231-6238. (doi: 10.1002/ejoc.200900835).

13. Delgado, J. L.; Osuna, S.; Bouit, P. A.; Martínez-Álvarez, R.; Espíldora, E.; Solà, M.*; Martín, N.* Competitive Retro-Cycloaddition Reaction in Fullerene Dimers connected through pyrrolidino-pyrazolino Rings, J. Org. Chem. 2009, 74, 8174-8180. (doi: 10.1021/jo901644b).

12. Izquierdo, M.; Osuna, S.; Filippone, S.; Martín-Domenech, A.; Solà, M.; Martín, N.* Regioselective Intramolecular Nucleophilic Addition of Alcohols to C60: One-step Formation of a cis-1 Bicyclic-fused Fullerene, J. Org. Chem. 2009, 74, 6253-6259. (doi: 10.1021/jo901171r).

11. Osuna, S.; Swart, M.; Baerends, E. J.; Bickelhaupt, F. M.* Solà, M.* Homolytic versus Heterolytic Dissociation in Diatomic Alkalimetal Halides. The effect of microsolvation. Chem. Phys. Chem. 2009, 10, 2955-2967. (doi: 10.1002/cphc.200900480).

10. Osuna, S.; Swart, M.*; Solà, M.* Reactivity and Regioselectivity of Noble Gas Endohedral Fullerenes Ng2@C60 (Ng = He–Xe). Chem. Eur. J. 2009, 15, 13111-13123. (doi: 10.1002/chem.200901224).

9. Osuna, S.; Houk, K. N.* Cycloaddition Reactions of Butadiene and 1,3-dipoles to Curved Arenes, Fullerenes, and Nanotubes: Theoretical Evaluation of the Role of Distortion Energies on Activation Barriers. Chem. Eur. J. 2009, 15, 13219-13231. (doi: 10.1002/chem.200901761).

8. Osuna, S.*; Torrent-Sucarrat, M.; Ewels, C. P.; Solà, M.; Geerlings, P.; Van Lier, G., Local Aromaticity of Pristine and Fluorinated Carbon Nanotubes. J. Nanosci. Nanotech. 2009, 9, 6078-6083. (doi: 10.1166/jnn.2009.1570).

7. Osuna, S.; Morera, J.; Cases, M.; Morokuma, K.; Solà, M.* The Diels-Alder Reaction between Cyclopentadiene and C60: An Analysis of the Performance of the ONIOM Method for the Study of Chemical Reactivity in Fullerenes and Nanotubes. J. Phys. Chem. A 2009, 113, 9721-9726. (doi: 10.1021/jp904294y).

6. Dachs, A.; Torrent, A.; Roglans, A.*; Parella, T.; Osuna, S.; Solà, M.* Rhodium(I)-Catalysed Intramolecular [2+2+2] Cyclotrimerisations of 15-, 20- and 25-Membered Azamacrocycles: Experimental and Theoretical Mechanistic Studies. Chem. Eur. J. 2009, 15, 5289-5300. (doi: 10.1002/chem.200802548).

5. Izquierdo, M.; Osuna, S.; Filippone, S.; Martín-Domenech, A.; Solà, M.*; Martín, N.* H-Bond-Assisted Regioselective (cis-1) Intramolecular Nucleophilic Addition of the Hydroxyl Group to [60]Fullerene. J. Org. Chem. 2009, 74, 1480-1487. (doi: 10.1021/jo802152x).

4. Osuna, S.; Swart, M.*; Solà, M.* The Diels Alder Reaction on the Endohedral Y3N@C78: The Importance of the Fullerene Strain Energy. J. Am. Chem. Soc. 2009, 131, 129-139. (doi: 10.1021/ja8048783).

3. Filippone, S. §; Barroso, M. I.; Martín-Domenech, A.; Osuna, S. §; Solà, M.*; Martín, N.* On the mechanism of the thermal retrocycloaddition of pyrrolidinofullerenes (retro-Prato reaction). Chem. Eur. J. 2008, 14, 5198-5206. (§: The authors contributed equally to the work: Correction. Chem. Eur. J. 2008, 14, 5709). (doi: 10.1002/chem.200800096).

2. Osuna, S.; Swart, M.*; Campanera, J.; Poblet, J.; Solà, M.* Chemical Reactivity of D3h C78 (Metallo) Fullerene: Regioselectivity Changes Induced by Sc3N Encapsulation. J. Am. Chem. Soc. 2008, 130, 6206-6214. (doi: 10.1021/ja711167v).

1. Osuna, S.; Poater, J.; Bofill, J. M.; Alemany, P.; Solà, M., Are nucleus-independent (NICS) and 1H NMR chemical shifts good indicators of aromaticity in p-stacked polyfluorenes? Chem. Phys. Lett. 2006, 428, 191-195.