Water‐Solvation‐Dependent Spin Transitions in Cobalt(II)‐Octacyanidometallate Complexes

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Water-Solvation-Dependent Spin Transitions in Cobalt(II)-Octacyanidometallate Complexes

The Front Cover shows the structural unit of the newly discovered [Co(terpy)2]3[W(CN)8]2 ⋅12H2O compound, terpy=2,2′:6′,2′′-terpyridine. This material can adopt diverse states: low-spin CoII and WV, S=1/2; high-spin CoII, S=3/2; and low-spin CoIII and WIV, S=0 (blue, purple, red, light blue, and pink polyhedra), depending on the treatment history of the sample. The fresh complex at 10 K has low-spin CoII and WV centers. Above 300 K, the material demonstrates thermal desolvation-assisted spin-crossover (DASCO), reaching complete high-spin CoII and WV states at 400 K. Next, Co3W2 , upon cooling, exhibits SCO on CoII. Interestingly, a humidity treatment of Co3W2 initiates a new effect of isothermal humidity-activated charge-transfer-induced spin transition (HACTIST) leading to the partial conversion of CoII…WV to CoIII…WIV pairs, which can be reversed by desolvation. More information can be found in the Research Article by O. Stefanczyk, S.-i. Ohkoshi and co-workers.


Linear (−)‐Zampanolide: Flexibility in Conformation–Activity Relationships

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Linear (−)-Zampanolide: Flexibility in Conformation–Activity Relationships

We developed a linear variant of the potent cytotoxic (−)-zampanolide that retains nanomolar activity towards cancer cell lines. In contrast to medicinal chemistry dogma, these results demonstrate that increased overall conformational flexibility is not necessarily detrimental to protein binding affinity and biological activity. High-field 2D-NMR, computational modeling, and antiproliferative assays were utilized to develop the conformation-activity relationship profile for this class of marine polyketide. This successful design strategy now provides three new sites for further analogue development; N-acyl hemiaminal side chain, C19 acyl group, and C9 ketone.


Abstract

Through an understanding of the conformational preferences of the polyketide natural product (−)-zampanolide, and the structural motifs that control these preferences, we developed a linear zampanolide analogue that exhibits potent cytotoxicity against cancer cell lines. This discovery provides a set of three structural handles for further structure-activity relationship (SAR) studies of this potent microtubule-stabilizing agent. Moreover, it provides additional evidence of the complex relationship between ligand preorganization, conformational flexibility, and biological potency. In contrast to medicinal chemistry dogma, these results demonstrate that increased overall conformational flexibility is not necessarily detrimental to protein binding affinity and biological activity.