The Hyperporphyrin Concept: A Contemporary Perspective

The Gouterman four-orbital model conceptualizes porphyrin UV−visible spectra as dominated by four frontier molecular orbitals-two nearly degenerate HOMOs and two exactly degenerate LUMOS under D4h symmetry. These are well separated from all the other molecular orbitals, and normal spectra involve transitions among these MOs. Unusual spectra occur when additional orbitals appear in this energy range, typically as a consequence of the central coordinated atom. For example, metals with empty d orbitals in a suitable energy range may lead to charge transfer from porphyrin (ligand) to metal, that is, so-called LMCT transitions. Metals with filled p or d orbitals may lead to charge transfer from metal to porphyrin, MLCT transitions. These cases lead to additional peaks and/or significant redshifts in the spectra and were classified as hyperporphyrins by Gouterman. Cases in which spectra are blueshifted were classified as hypsoporphyrins; they are common for relatively electronegative late transition metal porphyrins. Many of the same principles apply to porphyrin analogues, especially corroles. In this Perspective, we focus on two newer classes of hyperporphyrins: one reflecting substituent effects in protonated or deprotonated free-base tetraphenyporphyrins and the other reflecting “noninnocent” interactions between central metal ions and corroles. Hyperporphyrin effects on spectra can be dramatic, yet they can be generated by relatively simple changes and subtle structural variations, such as acid−base reactions or the selection of a central metal ion. These concepts suggest strategies for engineering porphyrin or porphyrinoid dyes for specific applications, especially those requiring far-red or near-infrared absorption or emission

A Critical Study on Acylating and Covalent Reversible Fragment Inhibitors of SARS-CoV-2 Main Protease Targeting the S1 Site with Pyridine

SARS coronavirus main proteases (3CL proteases) have been validated as pharmacological targets for the treatment of coronavirus infections. Current inhibitors of SARS main protease, including the clinically admitted drug nirmatrelvir are peptidomimetics with the downsides of this class of drugs including limited oral bioavailability, cellular permeability, and rapid metabolic degradation. Here, we investigate covalent fragment inhibitors of SARS Mpro as potential alternatives to peptidomimetic inhibitors in use today. Starting from inhibitors acylating the enzyme's active site, a set of reactive fragments was synthesized, and the inhibitory potency was correlated with the chemical stability of the inhibitors and the kinetic stability of the covalent enzyme-inhibitor complex. We found that all tested acylating carboxylates, several of them published prominently, were hydrolyzed in assay buffer and the inhibitory acyl-enzyme complexes were rapidly degraded leading to the irreversible inactivation of these drugs. Acylating carbonates were found to be more stable than acylating carboxylates, however, were inactive in infected cells. Finally, reversibly covalent fragments were investigated as chemically stable SARS CoV-2 inhibitors. Best was a pyridine-aldehyde fragment with an IC50 of 1.8 μM at a molecular weight of 211 g/mol, showing that pyridine fragments indeed are able to block the active site of SARS-CoV-2 main protease

A numerical modelling and simulation of core-scale sandstone acidizing process: a study on the effect of temperature

A wide and comprehensive understanding of the chemical reactions and mechanisms of HBF4 is crucial as it significantly influences its performance in stimulating a sandstone formation. In general, it is well-known that HBF4 is able to provide a deeper penetration into the sandstone matrix before being spent due to its uniquely slow hydrolysis ability to produce HF. In the present study, a 3D numerical modelling and simulation were conducted to examine the capability of HBF4 in enhancing the porosity and permeability of the sandstone matrix. The model is built in COMSOL® Multiphysics commercial software of computational fluid dynamics (CFD) to simulate the acid core flooding process on sandstone core. The model had been validated against the experimental data in the literature. The results matched with the measured plot data very well. The effect of temperature on the performance HBF4 sandstone acidizing is evaluated in this study. The simulation results indicated that at low temperature of 25 °C, HBF4 is not very effective, as justified in its poor porosity and permeability increments of only 1.07 and 1.23, respectively. However, at elevated temperatures, the porosity and permeability enhancement also become increasingly more significant, which showed 1.26 and 2.06, respectively, at 65 °C; and 1.67 and 7.06, respectively, at 105 °C. Therefore, one can conclude that HBF4 acid treatment performed better at elevated temperatures due to increased hydrolysis rate, which is a governing function in HBF4 sandstone acidizing. Overall, this model had provided a reliable alternative to optimize various other parameters of HBF4 acid treatment

Challenges of future multimedia QoE monitoring for internet service providers

The ever-increasing network traffic and user expectations at reduced cost make the delivery of high Quality of Experience (QoE) for multimedia services more vital than ever in the eyes of Internet Service Providers (ISPs). Real-time quality monitoring, with a focus on the user, has become essential as the first step in cost-effective provisioning of high quality services. With the recent changes in the perception of user privacy, the rising level of application-layer encryption and the introduction and deployment of virtualized networks, QoE monitoring solutions need to be adapted to the fast changing Internet landscape. In this contribution, we provide an overview of state-of-the-art quality monitoring models and probing technologies, and highlight the major challenges ISPs have to face when they want to ensure high service quality for their customers