Detection of SARS-CoV-2 using RT-PCR and other advanced methods can achieve high accuracy. However, their application is limited in countries that lack sufficient resources to handle large-scale testing during the COVID-19 pandemic. Here, we describe a method to detect SARS-CoV-2 in nasal swabs using matrix-assisted laser desorption/ionization mass spectrometry (MALDI-MS) and machine learning analysis. This approach uses equipment and expertise commonly found in clinical laboratories in developing countries. We obtained mass spectra from a total of 362 samples (211 SARS-CoV-2-positive and 151 negative by RT-PCR) without prior sample preparation from three different laboratories. We tested two feature selection methods and six machine learning approaches to identify the top performing analysis approaches and determine the accuracy of SARS-CoV-2 detection. The support vector machine model provided the highest accuracy (93.9%), with 7% false positives and 5% false negatives. Our results suggest that MALDI-MS and machine learning analysis can be used to reliably detect SARS-CoV-2 in nasal swab samples. The outbreak of coronavirus disease 2019 (COVID-19) is a crisis that affects rich and poor countries alike 1. Detection of SARS-CoV-2 in patient samples is a critical tool for monitoring spread of the disease, guiding therapeutic decisions and devising social distancing protocols 2. Detection assays based on RT-PCR are the most effective and sensitive method for diagnosis of SARS-CoV-2 infection and are used in laboratories around the world 3. However, some countries lack the laboratory resources and access to PCR kits to conduct testing at the required levels. Therefore, other reliable diagnostic techniques are needed. Most clinical diagnostic laboratories have MALDI-MS equipment, which is used to identify bacterial and fungal infections. We propose to leverage the ease-of-use and robustness of MALDI-MS pathogen identification for large-scale SARS-CoV-2 testing in developing countries. MALDI-MS-based assays rely on reference spectra of strains and bioinformatics for high-sensitivity and high-specificity species identification through proteomic profiling. This approach is well established and accepted in many countries for routine diagnostics of yeast and bacterial infections. However, no spectral libraries for SARS-CoV-2 identification using MALDI-MS are publicly available to our knowledge. We first acquired MALDI mass spectra of nasal swab samples that had been tested for SARS-CoV-2 by RT-PCR and analyzed them using machine learning (ML). In this experiment (Fig. 1a), a total of 362 samples (211 SARS-CoV-2-positive and 151 negative, unequivocally confirmed by PCR), which came from three different countries, Argentina (Lab 1), Chile (Lab 2) and Peru (Lab 3), were placed on the MALDI plate without prior sample purification.
The syntheses and structures of new bis-N-phenyl-4-cyano-β-diketiminate (1), bis-N-phenyl-2-cyano-β-diketiminate (2), N-phenyl-4-cyano-N-phenyl-2-cyano-β-diketiminate (3), N-phenyl-4-cyano-N-2,6-diisopropylphenyl-β-diketiminate (4), N-phenyl-2-cyano-N-2,6-diisopropylphenyl-β-diketiminate (5), and methallyl nickel complexes [L1Ni(η3-methallyl)] (6), [L2Ni(η3-methallyl)] (7), [L4Ni(η3-methallyl)] (8), and [L5Ni(η3-methallyl)] (9) from the reaction of deprotonated ligands 1/2, 4/5, and methallylnickel chloride dimer are reported. Subsequent reactions of complexes 6–9 with tris(pentafluorophenyl)boron give rise to new adducts [L1Ni(η3-methallyl)]·2B(C6F5)3 (10), [L2Ni(η3-methallyl)]·2B(C6F5)3 (11), [L4Ni(η3-methallyl)]·B(C6F5)3 (12), and [L5Ni(η3-methallyl)]·B(C6F5)3 (13), where B(C6F5)3 is coordinated to the cyano group. New compounds are characterized by NMR, IR, and mass spectrometry techniques, and crystal structures of most compounds are obtained and described. Complexes 6–9, adducts 10–13, and adducts 10–13 with 5 equiv of B(C6F5)3 have been investigated toward ethylene activation. Complexes 6–9 were inactive toward ethylene even at 60 °C, while adducts 10–13 showed reactivity toward ethylene; adding 5 equiv of B(C6F5)3 to adducts 10–13 leads to an increase in reactivity toward ethylene. Adducts 10 and 11 alone and with 5 equiv of B(C6F5)3 catalyze the oligomer formation, while adducts 12 and 13 by the same conditions catalyze the polyethylene formation. Adduct 13 activity is five times higher with respect to 12 at 50 °C and two times higher at 70 °C. The formation of branched moderate molecular weight PE by 12/B(C6F5)3 and 13/B(C6F5)3 is observed.
A cationic methallyl 2-pyridine-4,7-dimethoxybenzimidazole (L 1 ) nickel precatalyst is highly selective in ethene dimerizations to 1-butene. The same catalyst isomerizes 1-butene and 1-octene to internal olefins. Co-catalytic additives of B(C6F5)3 or BF3·OEt2 coordinate to the catalyst and increase the reaction rates of ethene dimerization. ESI-MS was applied identifying a [L 1 NiH]+ cation as the catalytically active species.
C–H activation of methane followed by dehydrocoupling at room temperature led ultimately to the formation of the olefin H2CCHtBu via the addition of redox-active ligands (L) such as thioxanthone or 2,2′-bipyridine (bipy) to (PNP)TiCHtBu(CH3) (1).
A new organocatalyst, the selenolate anion [RSe] -, generated from bench-stable and commercially available diphenyl diselenide or from phenyl benzyl selenide (10 mol%) is introduced. Benchmarking is performed in the conversion of benzylic chlorides into trans-stilbenes selectively at room temperature. Mechanistic studies support the intermediacy of the selenolate anion and of 1,2diphenylethyl phenyl selenide.
N-Arylcyano-b-diketiminate methallyl nickel complexes activated with B(C 6 F 5 ) 3 were used in the polymerization of ethylene. The microstructure analysis of obtained polyethylene (PE) was done by differential scanning calorimetry and 13 C nuclear magnetic resonance (NMR). The branched polymer structures produced by these catalysts were attributed to one step isomerization mechanism of the catalyst along the polymer chain. The ortho or para position of the cyano group with co-ordinated B(C 6 F 5 ) 3 in both methallyl nickel catalysts influenced the polymer molecular weight, branching, and consequently melting and crystallization temperatures. NMR spectroscopic studies showed predominantly the formation of methyl branches in the obtained PE. Catalysts under study gave linear low-density PEs with good crystallinities at temperatures of reaction between 50 C and 70 C at moderate pressures (12.3 atm). A propylene-ethylene copolymer produced by the metallocene catalyst had the same concentration of branches as the PE synthesized from methallyl nickel/B(C 6 F 5 ) 3 . Comparing the two polyolefins with the same degree of branching, it was observed that the polymer obtained with the nickel catalyst proved to be twice more crystalline and had greater T m .
A detailed quantum chemical study that analyzed the mechanism of ethylene oligomerization and polymerization by means of a family of four neutral methallyl Ni catalysts is presented. The role of the boron co-activators, BF and B(C F ) , and the position of ligand functionalization (ortho or para position of the N-arylcyano moiety of the catalysts) were investigated to explain the chain length of the obtained polymers. The chain initialization proceeded with higher activation barriers for the ortho-functionalized complexes (≈19 kcal mol ) than the para-substituted isomers (17-18 kcal mol ). Two main pathways were revealed for the chain propagation: The first pathway was favored when using the B(C F ) co-activated catalyst, and it produced long-chain polymers. A second pathway led to the β-hydrogen complexes, which resulted in chain oligomerization; this pathway was preferred when the BF co-activated catalysts were used. Otherwise, the termination of longer chains occurred via a stable hydride intermediate, which was formed with an energy barrier of about 14 kcal mol for the B(C F ) co-activated catalysts. Significant new insights were made into the reaction mechanism, whereby neutral methallyl Ni catalysts act in oligomerization and polymerization processes. Specifically, the role of co-activation and ligand functionalization, which are key information for the further design of related catalysts, were revealed.
The selenenate anion (RSeO À ) is introduced as an active organocatalyst for the dehydrohalogen coupling of benzyl halides to form trans-stilbenes. It is shown that RSeO À is a more reactive catalyst than the previously reported sulfur analogues (sulfenate anion, RSO À ) and selenolate anions (RSe À ) in the aforementioned reaction. This catalytic system was also applied to the benzylic-chloromethyl-coupling polymerization (BCCP) of a bis-chloromethyl arene to form ppv (poly(p-phenylene vinylene))-type polymers with high yields, M n (average molecular weight) up to 13,000 and Đ (dispersity) of 1.15.
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