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Water oxidation is a bottleneck reaction for the establishment of solar-to-fuel energy conversion systems. Earth-abundant metal-based polyoxometalates are promising heterogeneous water oxidation catalysts that can operate in a wide pH range. However, detailed structure-reactivity relationships are not yet comprehensively understood, hampering the design and synthesis of more effective polyoxometalate-based oxidation catalysts. Here we report the synthesis of an ordered, mixed-metal cobalt-iron Weakley archetype [CoII2(H2O)2FeIII2(CoIIW9O34)2]14− (Co2Fe2-WS), which unexpectedly highlights the strong influence of the central, coordinatively saturated metal ions on the catalytic water oxidation characteristics. The resulting species exhibits catalytic turnover frequencies which are up to 4× higher than those of the corresponding archetype tetracobalt-oxo species [CoII2(H2O)2CoII2(PW9O34)2]10− (Co4-WS). It is further striking that the system becomes catalytically inactive when one of the central positions is occupied by a WVI ion as demonstrated by [CoII2(H2O)2CoIIWVI(CoIIW9O34)2]12− (Co3W-WS). Importantly, this study demonstrates that coordinatively saturated metal ions in this central position, which at first glance appear insignificant, do not solely have a structural role but also impart a distinctive structural influence on the reactivity of the polyoxometalate. These results provide unique insights into the structure-reactivity relationships of polyoxometalates with improved catalytic performance characteristics.

Background: The efficacy and toxicity of olaparib as combination therapy in early breast cancer (BC) patients with homologous recombinant deficiency (HRD) [score high and/or germline (g) or tumour (t) BRCA1/2 mutation] is not well described. GeparOLA (ClinicalTriais gov, NCT02789332) investigated olaparib in combination with paclitaxel in HER2-negative early BC with HRD. Patients and methods: Patients with untreated primary HER2-negative cT2-cT4a-d or cT1c with either cN + or pNSIN + or cT1c and triple-negative breast cancer (TNBC) or cT1c and Ki-67>20% BC with HRD were randomised either to paclitaxel (P) 80 mg/m(2) weekly plus olaparib (0) 100 mg twice daily for 12 weeks or P plus carboplatinum (Cb) area under the curve 2 weekly for 12 weeks, both followed by epirubicin/cyclophosphamide (EC). Stratification factors were hormone receptor (HR) status (HR versus HR ) and age (<40 versus >= 40 years). The primary endpoint was pathological complete response (pCR; ypTO/is ypNO). A two-sided one-group chi(2)-test was planned to exclude a pCR rate of <= 55% in the PO-EC arm. Secondary end points were other pCR definitions, breast conservation rate, clinical/ imaging response, tolerability and safety. Results: A total of 107 patients were randomised between September 2016 and July 2018; 106 (PO N = 69; PCb N = 37) started treatment. Median age was 47.0 years (range 25.0-71.0); 36.2% had cT1, 61.0% cT2, 2.9% cT3, and 31.8% cN-positive tumours; grade 3 tumours: 86.8%; Ki-67>20%: 89.6%; TNBC: 72.6%; confirmed gBRCA1/2 mutation: 56.2%. The pCR rate with PO was 55.1% [90% confidence interval (CI) 44.5% to 65.3%] versus PCb 48.6% (90% CI 34.3% to 63.2%). Analysis for the stratified subgroups showed higher pCR rates with PO in the cohorts of patients <40 years and HR patients. Conclusion: GeparOLA could not exclude a pCR rate of <= 55% in the PO arm. PO was significantly better tolerated and the combination merits further evaluation.