Structural revisions of small molecules reported to cross-link G-quadruplex DNA in vivo reveal a repetitive assignment error in the literature

Yuan et al.1 recently published a paper entitled Existence of G-quadruplex structures in promoter region of oncogenes confirmed by G-quadruplex DNA cross-linking strategy. Their report is based on the synthesis and use of bis-imine 1 (Fig. 1). We found that this key compound is misassigned. From the body of evidence gathered in this letter it is apparent that in their study Yuan et al. used benzimidazole 1revised and not the isomeric bis-imine 1. Furthermore, to prove the existence of G-quadruplex structures in promoter region of oncogenes in vivo, the authors reported a carboxy-substituted derivative of bis-imine 1 which they used in a pull-down study (see compound 5, Fig. 2). We found that structural revision is also necessary in this case. As the targeting of G-quadruplex DNA holds considerable promise for anti-cancer therapy, the structural revisions presented herein are of importance for future research in this area2,3,4,5. Figure 1 Reaction leading to compound 1revised erroneously assigned as compound 1. Figure 2 Revised structure of the product generated in the catalyst-free reaction of diamine 4 with aldehyde 2. In addition, the assignment errors in the report by Yuan et al.1 led us to more general concerns about additional misassignments in cases of published bis-imines. This concerns bis-imines produced from 1,2-phenylenediamine and hydroxybenzaldehydes having no substituent in ortho-positions. As highlighted in this paper, any such published bis-imines lacking substantial NMR and/or X-ray crystal structure evidence should be taken with caution as they may actually be benzimidazoles and not bis-imines as documented for two further misassignments in the literature. As the chemistry of bis-imines with ortho-hydroxy group (salenes) and related compounds remains influential for development of molecular science (e.g. catalysis6,7,8,9, supramolecular10 and polymer science11,12, chemical biology13,14,15), the danger of propagation of errors in this and related fields is greater than in other branches of chemistry. It is therefore crucial to uncover examples of repetitive assignment errors and prevent their perpetuation, which is the main objective of this paper.