{rfName}
En

Indexed in

Citations

12

Altmetrics

Analysis of institutional authors

Garrido-Garcia, PabloAuthorRigotti, ThomasCorresponding AuthorTortosa, MariolaCorresponding Author

Share

March 10, 2025
Publications
>
Article
No

Enantioselective photocatalytic synthesis of bicyclo[2.1.1]hexanes as ortho-disubstituted benzene bioisosteres with improved biological activity

Publicated to: Nature Chemistry. 17 (5): 734-745 - 2025-02-25 17(5), DOI: 10.1038/s41557-025-01746-7

Authors: Garrido-García P; Quirós I; Milán-Rois P; Ortega-Gutiérrez S; Martín-Fontecha M; Campos LA; Somoza Á; Fernández I; Rigotti T; Tortosa M

Affiliations

Autonomous Univ Madrid, Fac Sci, Organ Chem Dept, Madrid, Spain - Author
Autonomous Univ Madrid, Inst Adv Res Chem Sci IAdChem, Madrid, Spain - Author
Ctr Innovat Adv Chem ORFEO CINQA, Madrid, Spain - Author
IMDEA Nanociencia, Madrid, Spain - Author
Univ Complutense Madrid, Fac Chem Sci, Organ Chem Dept, Madrid, Spain - Author
Univ Complutense Madrid, Fac Opt & Optometry, Organ Chem Dept, Madrid, Spain - Author
See more

Abstract

1,5-Disubstituted bicyclo[2.1.1]hexanes are bridged scaffolds with well-defined exit vectors that are becoming increasingly popular building blocks in medicinal chemistry because they are saturated bioisosteres of ortho-substituted phenyl rings. Here we have developed a Lewis-acid-catalysed [2 + 2] photocycloaddition to obtain these motifs as enantioenriched scaffolds, providing an efficient approach for their incorporation in a variety of drug analogues. Retention of the biological activity of the bicyclo[2.1.1]hexane-containing analogues in the specific proteins targeted by the original drugs has confirmed the suitability of this moiety to serve as a bioisostere of ortho-substituted phenyl rings. Moreover, we have studied the potential of the different enantiomers of the drug analogues to selectively induce cytotoxicity in a panel of tumour cell lines, observing markedly differential effects for the two enantiomers and a substantial improvement over the corresponding sp2-based drugs. This showcases that the control of the absolute configuration and tridimensionality of the drug analogue has a large impact on its biological properties.

Quality index

Bibliometric impact. Analysis of the contribution and dissemination channel

The work has been published in the journal Nature Chemistry due to its progression and the good impact it has achieved in recent years, according to the agency WoS (JCR), it has become a reference in its field. In the year of publication of the work, 2025, it was in position 10/239, thus managing to position itself as a Q1 (Primer Cuartil), in the category Chemistry, Multidisciplinary. Notably, the journal is positioned above the 90th percentile.

Independientemente del impacto esperado determinado por el canal de difusión, es importante destacar el impacto real observado de la propia aportación.

Según las diferentes agencias de indexación, el número de citas acumuladas por esta publicación hasta la fecha 2025-12-10:

  • Scopus: 8

Impact and social visibility

From the perspective of influence or social adoption, and based on metrics associated with mentions and interactions provided by agencies specializing in calculating the so-called "Alternative or Social Metrics," we can highlight as of 2025-12-10:

  • The use, from an academic perspective evidenced by the Altmetric agency indicator referring to aggregations made by the personal bibliographic manager Mendeley, gives us a total of: 16.
  • The use of this contribution in bookmarks, code forks, additions to favorite lists for recurrent reading, as well as general views, indicates that someone is using the publication as a basis for their current work. This may be a notable indicator of future more formal and academic citations. This claim is supported by the result of the "Capture" indicator, which yields a total of: 16 (PlumX).

With a more dissemination-oriented intent and targeting more general audiences, we can observe other more global scores such as:

  • The Total Score from Altmetric: 27.
  • The number of mentions on the social network X (formerly Twitter): 41 (Altmetric).

Leadership analysis of institutional authors

There is a significant leadership presence as some of the institution’s authors appear as the first or last signer, detailed as follows: First Author (GARRIDO GARCIA, PABLO) and Last Author (Tortosa Manzanares, Mariola).

the authors responsible for correspondence tasks have been RIGOTTI, THOMAS and Tortosa Manzanares, Mariola.

Awards linked to the item

Financial support was provided by the European Commission (ERC Consolidator Grant to M.T., grant number 101002715, and Marie Curie Postdoctoral Fellowship to T.R., grant number 101151954) and the Spanish Ministry of Science, Innovation and Universities (MICIU) and the Spanish State Research Agency (AEI) (grant number PID2022-142594NB-I00 to M.T., grant number PID2022-138797OB-I00 to S.O.-G., grant numbers PID2022-139318NB-I00 and RED2022-134331-T to I.F., grant number PID2020-119352RB-I00 and PID2023-146982OB-I00 to A.S.). A.S. thanks the Spanish Association Against Cancer (AECC), and IMDEA Nanociencia acknowledges support from the Spanish 'Severo Ochoa' Programme for Centres of Excellence in R&D (grant number CEX2020-001039-S). We acknowledge J. Perles and the Servicio Interdepartamental de Investigacion of UAM (SIdI-UAM) for X-ray structure analysis, and we thank J. M. Lassaletta and R. Fernandez (Universidad de Sevilla) for allowing us to use their HPLC equipment.