Design of Experiments for Optimization of Polyoxometalate Syntheses

Abstract

Design of experiments (DOE) is a key method for optimizing physical processes by altering multiple variables at once to assess their effect. In chemistry, DOE explores a wider parameter space than the dominant “One Factor at a Time” (OFAT) method providing greater opportunity to explore the factors that can be used to optimize yield, purity, and to explore chemical space for new compounds. One area of chemistry that suffers from low yields and poor reproducibility but is full of hard to predict and interesting materials is polyoxometalate cluster science. Herein, we developed a DOE analysis methodology to explore the parameter space of polyoxometalate cluster formation to explore the subtle input effects that are known to have an impact on the product discovery, purity, and stability under the preparation conditions. Using a Plackett–Burman screening design, we analyzed the effect of six synthetic parameters in only 12 experiments, following up with a full factorial analysis of the three most significant factors to identify the key parameters in the successful synthesis of each. Based on this, we provide a useful template that produces the input data for automated synthesis based on DOE on other synthetic procedures. In our POM test cases, redox agent stoichiometry was found in three of the four systems studied to be significant factors with pH and temperature, which also found to be commonly important. The insights derived from this analysis were applied to design optimized synthetic procedures and improve the yield of the product by on average >33% from the highest reported literature yield. Thus, the DOE methodology outlined here is shown to yield insights into reaction optimization rapidly with facile experimental design and analysis even for complex multivariate synthetic procedures.

A Brief Introduction to Chemical Reaction Optimization

“…DoE has been used extensively in the optimization of chemical processes, particularly in pharmaceutical and fine chemical settings. DoE is often used for studies relating to enhancing the yield − and purity − of particular products but is also used for drug formulations − and delivery, − analytical method development, − and more. − This is because there are numerous and undisputed benefits to the use of DoE for experimental parameter screening and optimization, especially when compared with traditional human intuition-guided experimentation. With the rise of user-friendly software packages and the increased awareness of the chemical community, there has been a large uptake of this statistical method in recent years, although the technique itself has been around since the mid-20th century .…”

Cerium-Encapsulated SbIII–SeIV-Templating Polyoxotungstate for Electrochemically Sensing Human Multidrug Resistance Gene Segment

“…As is known to all, the structural construction of POMs can be easily influenced by synthetic conditions. , Reviewing the synthesis of those reported two-story polyoxotungstates, it is found that the dosage of the second HA is 1.0–2.9 times of the first HA, while in our work, the molar ratio of the two HAs ([SeO 3 ] 2– : [SbO 3 ] 3– ) is about 5.0 (Table S2). Thus, the larger usage of the second HA is supposed to benefit the formation of the three-story {SbSe 2 W 21 } PBU.…”

A Data‐Driven Approach to Molten Salt Synthesis of N‐Rich Carbon Adsorbents for Selective CO2 Capture

“…[19] Such an approach, based on the classical "design of experiments" methodology, has recently shown success in the synthesis of complex nanomaterials but has yet to be applied to nanocarbon synthesis mediated by molten salts. [20][21][22][23][24] For molten salt synthesis of carbon nanomaterials, synthetic parameters of importance include the identity of organic precursors and salts; the salt:precursor ratio; and the thermal profile employed during synthesis. Each of these factors is hypothesized to uniquely impact the properties of the resulting carbon materials.…”

“…[ 19 ] Such an approach, based on the classical “design of experiments” methodology, has recently shown success in the synthesis of complex nanomaterials but has yet to be applied to nanocarbon synthesis mediated by molten salts. [ 20–24 ]…”