Pilot Study to Quantify Palladium Impurities in Lead-like Compounds Following Commonly Used Purification Techniques

Abstract

Palladium-catalyzed reactions are among the most commonly used procedures in organic synthesis. The products have a range of uses, including as intermediates in total synthesis and as screening compounds for drug discovery or agrochemical projects. Despite the known and potentially deleterious effects of low-level metal impurities in biological assays, the quantification of metal remaining in reaction products to verify the effective removal of the transition element is rarely reported. Using palladium as an exemplar, we describe a pilot study that for the first time quantifies residual metal levels in reaction products following increasingly rigorous purification protocols. Our results demonstrate that significant levels of residual palladium can remain in isolated reaction products following chromatographic purification, and only by using a subsequent metal scavenging step are they reliably reduced to a low level. Finally, we provide a set of simple guidelines that should minimize the potential for issues associated with residual palladium in reaction products.

Catalyst‐Free Visible Light Mediated Synthesis of Unsymmetrical Tertiary Arylphosphines

“…However, the efficiency of these methods is predicated on expensive or/and toxic metal catalysts [16] . Another serious concern for transition metal‐based reactions is that there is always a possibility for residual trace‐metal impurities to be present in the final products, unless special purification techniques are employed [17] . Metal impurities in organic compounds even at a very low level can severely affect their properties and reactivity.…”

“…[16] Another serious concern for transition metal-based reactions is that there is always a possibility for residual trace-metal impurities to be present in the final products, unless special purification techniques are employed. [17] Metal impurities in organic compounds even at a very low level can severely affect their properties and reactivity. In particular, trace-level impurities of Pd(0)À PR 3 species, survived a chromatography purification, have been demonstrated to cause a phantom reactivity of organic compounds and lead to mechanistic misinterpretations.…”

The Toxicological Risk Assessment (TRA) of Total Chromium Impurities in Menthae piperitae tinctura (Mentha x piperita L., folium) Available in Polish Pharmacies Including Regulatory Approaches with Special Emphasis of Cr Speciation and Genotoxicity

“…A review of the current literature shows that it is a very rare topic [4,5]. Studies including EI in herbal medicinal products available in pharmacies are dynamically developed by the group conducted by Jurowski et al [6][7][8][9].…”

A new chromone-based fluorescent probe for ratiometric detection of Pd2+

“…13,14 Owing to its thiophilic nature, palladium can bind with DNA, proteins and other macromolecules and perturb a range of cellular processes. [15][16][17] Environmental pollution emissions to water and soil may be the result of palladium residues in pharmaceutical compounds or in the environment, [18][19][20] thereby making the proposed maximum dietary intake for this ubiquitous and lethal heavy metal less than 1.5-15 g per person per day and its threshold in drugs is 5-10 ppm. 21 Furthermore, palladium also hampers the activity of many enzymatic reactions such as alkaline phosphatase, creatine kinase and prolyl hydroxylase.…”