Towards a quantitative understanding of palladium metal scavenger performance: an electronic structure calculation approach

Abstract

Dispersion corrected density functional theory (DFT-D) has been applied to understand the performance of several palladium metal scavengers. Nine different sulfur-based ligands and three different palladium metal sets have been investigated in detail. Based on a thorough analysis of the thermodynamic binding parameters ΔH, ΔG and ΔS, we have identified the best binding modes for all scavenger ligands. Bis-monodentate coordination is favoured over chelation in ΔH and ΔG values for most of the scavenger ligands. Special attention has been paid to the ligand strain energies, which account for the structural changes of the ligands upon complexation indicating that small (5-membered) chelates are considerably less favourable than expected. Some ligands can use their longest chain (>7-atoms) to yield trans chelates, which ligands with shorter chains (≤6-atoms) are unable to form. A secondary amino nitrogen (RR'NH) is found to be the best donor with highest binding enthalpy for Pd(ii) metal systems. In terms of the strength of the initial binding interactions, -SMe > -SH; capping thiols (-SH) as thioethers (-SMe) is therefore suggested to be an effective strategy in scavenger design. These observations mark the beginning of a knowledge base of the full range of possible interactions, leading to the construction of a sulfur ligand database for the design of scavenger systems.

Statistical DoE Approach to the Removal of Palladium from Active Pharmaceutical Ingredients (APIs) by Functionalized Silica Adsorbents

“…Scavenger screening studies within the pharmaceutical industry have regularly found SPM32 and other multifunctional silica scavengers to be more efficient for Pd removal and a computational study has recently been conducted to better understand the importance of the thioether unit in this regard. 27 The functional group loading (FGL) of the SPM32 scavenger comprises between 0.8 and 1.1 mmol of functional group per gram of silica, with the FGL of the particular batch of scavenger used in this study measured at 0.93 mmol/g (see section 2, Supporting Information).…”

Definition of Design Spaces Using Mechanistic Models and Geometric Projections of Probability Maps

“…The column packing material, a silica-based thiol-functionalized scavenger, is used to break down Pd complexes in solution and promote binding to the metal. Recent publications , reported that Pd speciation affects the performance of metal scavenging processes. The detrimental impact of dissolved oxygen to scavenging performance has been confirmed experimentally in our laboratories.…”

Third-Generation Method for High-Throughput Quantification of Trace Palladium by Color or Fluorescence

“…Therefore, process chemists must develop a specific and highly efficient palladium-scavenging protocol for each API to meet the safety regulation. This is accomplished through screenings of dozens of potential workup protocols and scavengers, among other purification techniques. − This process generates several dozens of samples in which to quantify palladium. Meanwhile, new scavengers continue to emerge, ,− adding options to explore.…”