• Controlled olefin polymerization catalysts (Macromolecules 2004, 37, 8201)

  • Molecular kinetics of olefin polymerization (JACS 2010, 132, 13651)

  • Structure-activity relationships in molecular catalysis (Macromolecules 2012, 45, 4046)

  • Computational modeling of industrial Ziegler-Natta catalysts (J. Catal. 2012, 286, 103)

  • Microstructural study of PP ‘chain shuttling’ (Macromolecules 2007, 40, 7736)



LSP strives for originality and state-of-the-art character of vision and toolbox; therefore, a careful analysis of the emerging trends is at the foundation of its approach. An important element to consider is that, despite the tremendous progress in the last decades, the science of catalysis remains far from exact, even when the active species is a well-defined molecular entity. Discovering a new selective catalyst is always a labour and capital intensive tentative process. Hence, High Throughput Experimentation (HTE) tools and methods are more and more used in this context. Originally implemented in the pharmaceutical industry for the discovery and optimization of novel drugs with a combinatorial approach, HTE methodologies have spread into organometallic catalysis and are now used for parallel catalyst synthesis and screening.

A typical HTE workflow for catalyst discovery and optimization in industry, structured in three stages, is shown in Figure 2-left. The first stage applies a primary screen in which a very large number of experiments (~103/day) in very small scale (< 1 mL) are dedicated to rapid discovery of catalyst structures which are promising in at least some respects (‘hits’); in this, precision can be traded for throughput, and qualitative trends are more important than precise data. Hits identified at this stage are then verified and improved in a subsequent secondary screening stage, in which the catalyst performance properties for the targeted application are assessed using larger scales (in relative sense! 1-10 mL), with less experiments (~102/day ‘only’) run under more commercially relevant conditions. In a tertiary stage, catalysts that meet most or all predetermined performance criteria (‘leads’) are then optimized through structural elaboration, and scale-up experiments in miniature or pilot plants, in which precise kinetic data are collected in order to generate candidates for commercial development. The first successful case histories of this approach reported in the open literature demonstrate a substantial decrease of the time span from the initial discovery of a new catalyst and its commercial exploitation. However, the process remains in essence empirical.

LSP Research Approach New Figure2

Figure 2. High-throughput-based approaches to [polyolefin] catalysis. Left: HTE workflow for trial-and-error catalyst discovery (*Pilot stage is not high-throughput). Right: The LSP HTC&HTE loop for catalyst fine-tuning/optimization.


On the other hand, the ability to design a catalyst, i.e. the rational implementation of a molecular or supra-molecular entity functional to a given chemical transformation, has long been claimed by organometallic chemists working in academia. In reality, many catalytic processes have been well-understood ex-post at molecular level, in homogeneous and even – to some extent – heterogeneous phase, but the number of chemical and physical variables that must be managed in order to predict catalytic reactivity and design new catalysts from scratch is still prohibitively high for a conventional approach.

In view of all this, LSP implemented an innovative approach using integrated HTC&HTE methods. HTC stands for High Throughput Computation; the tremendous progress of Computational Chemistry makes it possible to run realistic organometallic chemistry experiments in-silico, and steer or interpret real-world ones. In brief, our strategy (Figure 2-right) is to:

i) replace the highly demanding and expensive experimental primary HTE screening with an in-silico equivalent, namely a HTC pre-screening of molecular or heterogeneous catalysts;

ii) increase the accuracy of the secondary HTE screening in mini-reactors (~50 polymerization experiments per day with a full and quantitative evaluation of the polymerization kinetics and molecular characterization of the polymers produced);

iii) connect the HTC and HTE parts in a self-sustaining feedback loop configuration;

iv) use the HTC&HTE results for the rapid build-up of robust databases of structure/activity relationships, and implement ‘white-box’ and/or ‘black-box’ QSAR models with predictive ability.

In doing this, we did not cut our roots. A most important traditional asset of LSP is the ability to ‘fingerprint’ the active sites of olefin polymerization catalysts by means of 13C NMR analyses of polymer microstructure. This ability still represents an integral part of the novel HTC&HTE approach, thanks to the implementation of the latest high-temperature cryoprobe NMR technology, enabling us to characterize up to 50 polyolefin samples per day by 13C NMR. Along with further high-throughput analytical tools such as Rapid GPC and analytical Crystallization Elution Fractionation, all integrated with the secondary screening HTE platforms, this guarantees that speed in data acquisition is not to the expense of data quality and significance.  More information can be found at the Equipment page.


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