Self‐Assembly of Halogenated Cobaltacarborane Compounds: Boron‐Assisted CH⋅⋅⋅XB Hydrogen Bonds?

Planas, José Giner; Teixidor, Francesç; Viñas, Clara; Light, Mark E.; Hursthouse, Michael B.

doi:10.1002/chem.200601297

Cited by 22 publications

(4 citation statements)

References 62 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Among the 2,462 PDB structures that have heavy halogenated ligands, 791 structures were found to possess 1,295 halogen bonds. If using X···Y distances less than ΣvdW + 0.2 Å to account for uncertainties in the structures, , 1,894 halogen bonds were observed in 1,006 PDB structures. As shown in Figure a, 75.0% of the structures are determined by X-ray crystallography with a resolution better than 2.5 Å, while 0.8% are determined by solution NMR (high quality structures).…”

Section: Resultsmentioning

confidence: 99%

Halogen Bond: Its Role beyond Drug–Target Binding Affinity for Drug Discovery and Development

Yang

Liu

et al. 2014

J. Chem. Inf. Model.

340

300

View full text Add to dashboard Cite

Halogen bond has attracted a great deal of attention in the past years for hit-to-lead-to-candidate optimization aiming at improving drug-target binding affinity. In general, heavy organohalogens (i.e., organochlorines, organobromines, and organoiodines) are capable of forming halogen bonds while organofluorines are not. In order to explore the possible roles that halogen bonds could play beyond improving binding affinity, we performed a detailed database survey and quantum chemistry calculation with close attention paid to (1) the change of the ratio of heavy organohalogens to organofluorines along the drug discovery and development process and (2) the halogen bonds between organohalogens and nonbiopolymers or nontarget biopolymers. Our database survey revealed that (1) an obviously increasing trend of the ratio of heavy organohalogens to organofluorines was observed along the drug discovery and development process, illustrating that more organofluorines are worn and eliminated than heavy organohalogens during the process, suggesting that heavy halogens with the capability of forming halogen bonds should have priority for lead optimization; and (2) more than 16% of the halogen bonds in PDB are formed between organohalogens and water, and nearly 20% of the halogen bonds are formed with the proteins that are involved in the ADME/T process. Our QM/MM calculations validated the contribution of the halogen bond to the binding between organohalogens and plasma transport proteins. Thus, halogen bonds could play roles not only in improving drug-target binding affinity but also in tuning ADME/T property. Therefore, we suggest that albeit halogenation is a valuable approach for improving ligand bioactivity, more attention should be paid in the future to the application of the halogen bond for ligand ADME/T property optimization.

show abstract

Section: Resultsmentioning

confidence: 99%

Halogen Bond: Its Role beyond Drug–Target Binding Affinity for Drug Discovery and Development

Yang

Liu

et al. 2014

J. Chem. Inf. Model.

340

300

View full text Add to dashboard Cite

show abstract

“…The great potential of ortho ‐carboranes (1,2‐dicarba‐ closo ‐dodecaboranes) as building blocks in supramolecular chemistry,1 including the relevant areas of host–guest chemistry2–7 and crystal engineering8–10 has been recently reported. These structures are usually enabled in the solid state by hydrogen bonds involving the C cluster H vertices (abbreviated as C c H vertices),10, 11 including the contribution of weak interactions such as the dihydrogen bonds 12. Furthermore, the ortho ‐carborane cage can be selectively functionalized, allowing the rational design of a number of derivatives13 that are potentially able to participate in a large diversity of intermolecular interactions.…”

Section: Introductionmentioning

confidence: 99%

Iodinated ortho‐Carboranes as Versatile Building Blocks to Design Intermolecular Interactions in Crystal Lattices

Puga

Teixidor

Sillanpää

et al. 2009

Chemistry A European J

Self Cite

View full text Add to dashboard Cite

The crystal structures of numerous iodinated ortho-carboranes have been studied, which has revealed the diversity of intermolecular interactions that these substances can adopt in the solid state. The nature-mostly as it relates to hydrogen and/or halogen bonds-and relative strength of such interactions can be adjusted by selectively introducing substituents onto the cluster, thus enabling the rational design of crystal lattices. In this work we present the newly determined crystal structures of the following iodinated ortho-carboranes: 9-I-1,2-closo-C(2)B(10)H(11), 4,5,7,8,9,10,11,12-I(8)-1,2-closo-C(2)B(10)H(4), 3,4,5,6,7,8,9,10,11,12-I(10)-1,2-closo-C(2)B(10)H(2), 1-Me-8,9,10,12-I(4)-1,2-closo-C(2)B(10)H(7), 1,2-Me(2)-8,9,10,12-I(4)-1,2-closo-C(2)B(10)H(6), and 1,2-Ph(2)-8,9,10,12-I(4)-1,2-closo-C(2)B(10)H(6). Their 3D supramolecular organization has been thoroughly investigated and compared to similar previously published crystal structures. Such a systematic survey has allowed us to draw some general trends. C(c)-HI--B hydrogen bonds (C(c)= cluster carbon atoms) appear to be significant in the growth of the crystal lattices of these compounds, given the acidity of hydrogen atoms bonded to C(c), and the polarization of B-I bonds. These hydrogen bonds can be disrupted by selectively blocking the positions next to C(c), that is, B(3) and B(6), with bulky substituents that prevent iodine atoms from approaching as hydrogen acceptors. Halogen bonds of the type B-II-B are frequently observed in most cases, thus suggesting that these interactions could be attractive in boron clusters. In addition, different substituents can be grafted onto the ortho-carborane surface, thereby providing further possibilities for homomeric or heteromeric molecular assembly.

show abstract

“…Consequently, we decided to test a different approach based on derivatives of cobalt bis(1,2-dicarbollide) with arrested rotation and containing a phosphorothioate bridging moiety, namely, 13. We hypothesize that the reasons for the limited susceptibility of the type 8 compounds to functionalization on carbon atoms may include the electron-donating effect of boron cluster ligands; steric hindrance due to the presence of large substituents at the 8 and 8 positions, thereby hampering the electrophile's access to the activated carbon atoms; the formation of intramolecular hydrogen bonds between the oxygen atoms of the substituents at the 8,8 position and acidic carborane C-H groups (Figure 1) analogously to C-H•••X-B hydrogen bonds [27,28]; and rotations of 1,2-dicarbollide ligands around an axis, thereby decreasing the susceptibility of C-H groups to activation and alkylation. Consequently, we decided to test a different approach based on derivatives of cobalt bis(1,2-dicarbollide) with arrested rotation and containing a phosphorothioate bridging moiety, namely, 13.…”

Section: Resultsmentioning

confidence: 99%

Metallacarborane Synthons for Molecular Construction—Oligofunctionalization of Cobalt Bis(1,2-dicarbollide) on Boron and Carbon Atoms with Extendable Ligands

2023

View full text Add to dashboard Cite

The exploitation of metallacarboranes’ potential in various fields of research and practical applications requires the availability of convenient and versatile methods for their functionalization with various functional moieties and/or linkers of different types and lengths. Herein, we report a study on cobalt bis(1,2-dicarbollide) functionalization at 8,8′-boron atoms with different hetero-bifunctional moieties possessing a protected hydroxyl function allowing further modification after deprotection. Moreover, an approach to the synthesis of three and four functionalized metallacarboranes, at boron and carbon atoms simultaneously via additional functionalization at carbon to obtain derivatives carrying three or four rationally oriented and distinct reactive surfaces, is described.

show abstract

Self‐Assembly of Halogenated Cobaltacarborane Compounds: Boron‐Assisted CH⋅⋅⋅XB Hydrogen Bonds?

Cited by 22 publications

References 62 publications

Halogen Bond: Its Role beyond Drug–Target Binding Affinity for Drug Discovery and Development

Halogen Bond: Its Role beyond Drug–Target Binding Affinity for Drug Discovery and Development

Iodinated ortho‐Carboranes as Versatile Building Blocks to Design Intermolecular Interactions in Crystal Lattices

Metallacarborane Synthons for Molecular Construction—Oligofunctionalization of Cobalt Bis(1,2-dicarbollide) on Boron and Carbon Atoms with Extendable Ligands

Contact Info

Product

Resources

About