Design and Synthesis of Kekulè and Non-Kekulè Diradicaloids via the Radical Periannulation Strategy: The Power of Seven Clar's Sextets.

This work introduces an approach to uncoupling electrons via maximum utilization of localized aromatic units, i.e., the Clar's π-sextets. To illustrate the utility of this concept to the design of Kekulé diradicaloids, we have synthesized a tridecacyclic polyaromatic system where a gain of five Clar's sextets in the open-shell form overcomes electron pairing and leads to the emergence of a high degree of diradical character. According to unrestricted symmetry-broken UCAM-B3LYP calculations, the singlet diradical character in this core system is characterized by the y0 value of 0.98 (y0 = 0 for a closed-shell molecule, y0 = 1 for pure diradical). The efficiency of the new design strategy was evaluated by comparing the Kekulé system with an isomeric non-Kekulé diradical of identical size, i.e., a system where the radical centers cannot couple via resonance. The calculated singlet-triplet gap, i.e., the ΔEST values, in both of these systems approaches zero: -0.3 kcal/mol for the Kekulé and +0.2 kcal/mol for the non-Kekulé diradicaloids. The target isomeric Kekulé and non-Kekulé systems were assembled using a sequence of radical periannulations, cross-coupling, and C-H activation. The diradicals are kinetically stabilized by six tert-butyl substituents and (triisopropylsilyl)acetylene groups. Both molecules are NMR-inactive but electron paramagnetic resonance (EPR)-active at room temperature. Cyclic voltammetry revealed quasi-reversible oxidation and reduction processes, consistent with the presence of two nearly degenerate partially occupied molecular orbitals. The experimentally measured ΔEST value of -0.14 kcal/mol confirms that K is, indeed, a nearly perfect singlet diradical.

Alkaloids from Cryptolepis sanguinolenta as Potential Inhibitors of SARS-CoV-2 Viral Proteins: An In Silico Study.

The ongoing global pandemic caused by the human coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has infected millions of people and claimed hundreds of thousands of lives. The absence of approved therapeutics to combat this disease threatens the health of all persons on earth and could cause catastrophic damage to society. New drugs are therefore urgently required to bring relief to people everywhere. In addition to repurposing existing drugs, natural products provide an interesting alternative due to their widespread use in all cultures of the world. In this study, alkaloids from Cryptolepis sanguinolenta have been investigated for their ability to inhibit two of the main proteins in SARS-CoV-2, the main protease and the RNA-dependent RNA polymerase, using in silico methods. Molecular docking was used to assess binding potential of the alkaloids to the viral proteins whereas molecular dynamics was used to evaluate stability of the binding event. The results of the study indicate that all 13 alkaloids bind strongly to the main protease and RNA-dependent RNA polymerase with binding energies ranging from -6.7 to -10.6 kcal/mol. In particular, cryptomisrine, cryptospirolepine, cryptoquindoline, and biscryptolepine exhibited very strong inhibitory potential towards both proteins. Results from the molecular dynamics study revealed that a stable protein-ligand complex is formed upon binding. Alkaloids from Cryptolepis sanguinolenta therefore represent a promising class of compounds that could serve as lead compounds in the search for a cure for the corona virus disease.

Real-time evaluation of ventilation filter-bank systems.

This study evaluated two government facility ventilation systems. One was a metropolitan government office complex with a recirculation system where outside air was the makeup air; the other was a NIOSH facility that used 100% outside air with no recirculation. The methodology employed was a modified American Society of Agricultural Engineers standard (S525) for testing total enclosure filtration efficiency, in agricultural tractor cabs, with optical particle counters (OPC). The low-efficiency bag filters were tested when new and after being in the ventilation system for 3 months. The replacement medium-efficiency filters were evaluated for 6 months (the manufacturer's suggested change-out schedule). These eight-chamber, medium-efficiency filters had an increased filter surface area that resulted in increased airflow through the system. Unfortunately, these filters contained electrostatic filter media and lost filtration efficiency rapidly, which was subsequently confirmed in a 30-day study conducted to determine an appropriate change-out schedule for the eight-chamber bag filters. The study determined that less than 6 months' use was justified due to the reduced efficiency of the electrostatic filter media. The NIOSH facility's air handler #8 (100% outside air unit) was upgraded from electrostatic bag filters, which had a suggested 9-month change-out schedule, to V Bank mechanical, wet-laid, glass fiber filters. The results of a 3-year evaluation showed that the V Bank filters had better filter efficiency after 3 years of service than the electrostatic filters had at 9 months. Both studies employed matched OPC instruments to reduce instrument-to-instrument bias. The methodology is adaptable to monitoring the total efficiency of most air filtration systems, and results can help make decisions about upgrading filter performance.