Ir(III) and Ru(II) Complexes in Photoredox Catalysis and Photodynamic Therapy: A New Paradigm towards Anticancer Applications

Individually, photoredox catalysis (PC) and photodynamic therapy (PDT) are well-established concepts that have experienced a remarkable resurgence in recent years, leading to significant progress in organic synthesis for PC and clinical approval of anticancer drugs for PDT. But, very recently, new photoredox catalyst systems based on Ir(III) and Ru(II) complexes have garnered significant interest because they can simultaneously be used as PDT agents apart from their demonstrated PC activity. This highlight discusses the unique PC behavior of emerging Ir(III)- and Ru(II)-based systems while also examining their potential PDT activity in cancer treatment.     

A mineralogical approach to evaluating laboratory scale acid rock drainage characterisation tests

Effective management of the risks associated with acid rock drainage (ARD) requires the ability to identify material with a potential to generate ARD reliably. With the increasing prevalence of quantitative mineralogy (Quantitative XRD, auto-SEM), opportunity exists to use mineralogy at all stages in ARD characterisation and prediction. This study uses a mineralogical approach across the head grade samples and the residues obtained under leach conditions of several common ARD characterisation tests (Acid Neutralising Capacity, Net Acid Generation), as well as the University of Cape Town (UCT) biokinetic test to evaluate the extent to which acid-neutralising minerals react. The results show the contribution of the carbonates to the acid neutralising capacity, as well as the partial dissolution of intermediate weathering silicate minerals such as chlorite and mica.     

Evaluation of the degree of rate control via automatic differentiation

The degree of rate control (DRC) quantitatively identifies the kinetically relevant (sometimes known as rate-limiting) steps of a complex reaction network. This concept relies on derivatives which are commonly implemented numerically, for example, with finite differences (FDs). Numerical derivatives are tedious to implement, and can be problematic, and unstable or unreliable. In this study, we demonstrate the use of automatic differentiation (AD) in the evaluation of the DRC. AD libraries are increasingly available through modern machine learning frameworks. Compared with the FDs, AD provides solutions with higher accuracy with lower computational cost. We demonstrate applications in steady-state and transient kinetics. Furthermore, we illustrate a hybrid local-global sensitivity analysis method, the distributed evaluation of local sensitivity analysis, to assess the importance of kinetic parameters over an uncertain space. This method also benefits from AD to obtain high-quality results efficiently.     

Alteration of the Route to Menaquinone towards Isochorismate-Derived Metabolites

Chorismate and isochorismate constitute branch-point intermediates in the biosynthesis of many aromatic metabolites in microorganisms and plants. To obtain unnatural compounds, we modified the route to menaquinone in Escherichia coli. We propose a model for the binding of isochorismate to the active site of MenD ((1R,2S, 5S,6S)-2-succinyl-5-enolpyruvyl-6-hydroxycyclohex-3-ene-1-carboxylate (SEPHCHC) synthase) that explains the outcome of the native reaction with α-ketoglutarate. We have rationally designed variants of MenD for the conversion of several isochorismate analogues. The double-variant Asn117Arg–Leu478Thr preferentially converts (5S,6S)-5,6-dihydroxycyclohexa-1,3-diene-1-carboxylate (2,3-trans-CHD), the hydrolysis product of isochorismate, with a >70-fold higher ratio than that for the wild type. The single-variant Arg107Ile uses (5S,6S)-6-amino-5-hydroxycyclohexa-1,3-diene-1-carboxylate (2,3-trans-CHA) as substrate with >6-fold conversion compared to wild-type MenD. The novel compounds have been made accessible in vivo (up to 5.3 g L⁻¹). Unexpectedly, as the identified residues such as Arg107 are highly conserved (>94 %), some of the designed variations can be found in wild-type SEPHCHC synthases from other bacteria (Arg107Lys, 0.3 %). This raises the question for the possible natural occurrence of as yet unexplored branches of the shikimate pathway.     

The influence of sonication time on the biogenic amines formation as a critical point in uncured dry-fermented beef manufacturing

In this study, the influence of sonication time on the biogenic amines formation as a critical point in uncured dry-fermented beef manufacturing was studied. Samples of musculus semimembranosus were sonicated at different times (5 and 10 min) using ultrasound cold bath (4 °C) in acid whey (US 40 kHz and acoustic power 480 W). The effect of sonication on biogenic amine (BA) formation was investigated during 93 days of ripening period. Other parameters (pH value, water activity, microbial counts) that might provide further information on the product under study were also determined. The use of ultrasound during beef marinating in acid whey has a positive effect on retarding histamine (HIS), cadaverine (CAD), tyramine (TYR) and putrescine (PUT) formation. Moreover, the sonication treatment did not inhibit the growth of lactic acid bacteria (LAB) in dry-fermented beef during the whole ripening period. The pathogen bacteria (Staphylococcus aureus, Clostridium sp., Listeria monocytogenes) were not detected in all samples neither after 31 nor after 93 days of ripening period.