Decoding the CO2 Reduction Mechanism of a Highly Active Organometallic Manganese Electrocatalyst: Direct Observation of a Hydride Intermediate and Its Implications

A detailed mechanistic study of the electrochemical CO2 reduction catalyzed by the fac-[Mn-I(CO)(3)(bis-(NHC)-N-Me)MeCN](+) complex (1-MeCN+ ) is reported herein by combining in situFTIR spectroelectrochemistry(SEC), synthesis and characterization of catalytic intermediates,and DFT calculations. Under low proton concentrations, 1-MeCN+ efficiently catalyzes CO2 electroreductionwith long catalyst durability and selectivity toward CO (ca. 100%). The [Mn-I(CO)(3)(bis-(NHC)-N-Me)](-) anion (1(-) ) and the tetracarbonyl [Mn-I(CO)(4)(bis-(NHC)-N-Me)](+) complex (1-CO+ )are key intermediates of the catalytic CO2-to-CO mechanismdue to their impact on the selectivity and the reaction rate, respectively.Increasing the proton concentration increases formate production (upto 15% FE), although CO remains the major product. The origin of formateis ascribed to the competitive protonation of 1(-) to form a Mn(I) hydride (1-H), detected by SECin the absence of CO2. 1-H was also synthesizedand thoroughly characterized, including by X-ray diffraction analysis.Stoichiometric reactivity studies of 1-H with CO2 and labeled (CO2)-C-13 indicate a fast formationof the corresponding neutral Mn(I) formate species (1-OCOH) at room temperature. DFT modeling confirms the intrinsic capabilityof 1-H to undergo hydride transfer to CO2 dueto the strong & sigma;-donor properties of the bis-(Me)NHCmoiety. However, the large potential required for the HCOO- release from 1-OCOH limits the overall catalytic CO2-to-HCOO- cycle. Moreover, the experimentallyobserved preferential selectivity for CO over formate is dictatedby the shallow kinetic barrier for CO2 binding to 1(-) compared to the Mn-H bond formation.The detailed mechanistic study highlights the reduction potential,pK (a), and hydricity of the metal hydrideintermediate as crucial factors affecting the CO2RR selectivityin molecular systems

Automated HIV screening in the emergency department –earlier diagnosis, improved clinical outcomes

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Antimicrobial Activity of Manganese(I) Tricarbonyl Complexes Bearing 1,2,3-Triazole Ligands

Funding Information: We are grateful to Fundação para a Ciência e a Tecnologia, I.P., through DOI 10.54499/PTDC/QUI-QIN/0359/2021, MOSTMICRO- ITQB R&D Unit (UIDB/04612/2020 and UIDP/04612/2020) and LS4FUTURE Associated Laboratory (LA/P/0087/2020). The NMR data were acquired at CERMAX, ITQB NOVA, Oeiras, Portugal, with equipment funded by FCT, project AAC 01/SAIC/2016. Oscar A. Lenis-Rojas acknowledge national funds through FCT, POPH-Programa Operacional Potencial Humano, and FSE (European Social Fund) for the CEEC 2017 Initiative. This work was partially funded by the Department of Microbiology, Trinity College Dublin, Ireland. C. Trigueiros’ work is funded under a Provost Ph.D. Award provided by Trinity College Dublin, Dublin, Ireland. Funding of the Martins lab is also supported by Welcome Trust. This work was supported by the Associate Laboratory for Green Chemistry- LAQV, UCIBIO, and i4HB, which are financed by national funds from FCT/MCTES (UIDB/50006/2020, UIDP/50006/2020 and LA/P/0008/2020, UIDB/04378/2020 and UIDP/04378/2020, and LA/P/0140/2020, respectively). The X-ray infrastructure was financed by FCT-MCTES through project RECI/BBB-BEP/0124/2012. Publisher Copyright: © 2023 by the authors.Background. Antimicrobial resistance is one of the most pressing health issues of our time. The increase in the number of antibiotic-resistant bacteria allied to the lack of new antibiotics has contributed to the current crisis. It has been predicted that if this situation is not dealt with, we will be facing 10 million deaths due to multidrug resistant infections per year by 2050, surpassing cancer-related deaths. This alarming scenario has refocused attention into researching alternative drugs to treat multidrug-resistant infections. Aims. In this study, the antimicrobial activities of four manganese complexes containing 1,2,3,-triazole and clotrimazole ligands have been evaluated. It is known that azole antibiotics coordinated to manganese tricarbonyl complexes display interesting antimicrobial activities against several microbes. In this work, the effect of the introduction of 1,2,3,-triazole-derived ligands in the [Mn(CO)3(clotrimazole)] fragment has been investigated against one Gram-positive bacterium and five Gram-negative bacteria. Methods. The initial antimicrobial activity of the above-mentioned complexes was assessed by determining the minimum inhibitory and bactericidal concentrations using the broth microdilution method. Growth curves in the presence and absence of the complexes were performed to determine the effects of these complexes on the growth of the selected bacteria. A possible impact on cellular viability was determined by conducting the MTS assay on human monocytes. Results. Three of the Mn complexes investigated (4–6) had good antimicrobial activities against all the bacteria tested, with values ranging from 1.79 to 61.95 µM with minimal toxicity. Conclusions. Due to the increased problem of antibiotic resistance and a lack of new antibacterial drugs with no toxicity, these results are exciting and show that these types of complexes can be an avenue to pursue in the future.publishersversionpublishe

A Confidence Interval for the Wallace Coefficient of Concordance and Its Application to Microbial Typing Methods

Very diverse research fields frequently deal with the analysis of multiple clustering results, which should imply an objective detection of overlaps and divergences between the formed groupings. The congruence between these multiple results can be quantified by clustering comparison measures such as the Wallace coefficient (W). Since the measured congruence is dependent on the particular sample taken from the population, there is variability in the estimated values relatively to those of the true population. In the present work we propose the use of a confidence interval (CI) to account for this variability when W is used. The CI analytical formula is derived assuming a Gaussian sampling distribution and recurring to the algebraic relationship between W and the Simpson's index of diversity. This relationship also allows the estimation of the expected Wallace value under the assumption of independence of classifications. We evaluated the CI performance using simulated and published microbial typing data sets. The simulations showed that the CI has the desired 95% coverage when the W is greater than 0.5. This behaviour is robust to changes in cluster number, cluster size distributions and sample size. The analysis of the published data sets demonstrated the usefulness of the new CI by objectively validating some of the previous interpretations, while showing that other conclusions lacked statistical support

High Frequency of Copy Number Variations and Sequence Variants at CYP21A2 Locus: Implication for the Genetic Diagnosis of 21-Hydroxylase Deficiency

BACKGROUND: The systematic study of the human genome indicates that the inter-individual variability is greater than expected and it is not only related to sequence polymorphisms but also to gene copy number variants (CNVs). Congenital Adrenal Hyperplasia due to 21-hydroxylase deficiency (21OHD) is the most common autosomal recessive disorder with a carrier frequency of 1:25 to 1:10. The gene that encodes 21-hydroxylase enzyme, CYP21A2, is considered to be one of the most polymorphic human genes. Copy number variations, such as deletions, which are severe mutations common in 21OHD patients, or gene duplications, which have been reported as rare events, have also been described. The correct characterization of 21OHD alleles is important for disease carrier detection and genetic counselling METHODOLOGY AND FINDINGS: CYP21A2 genotyping by sequencing has been performed in a random sample of the Spanish population, where 144 individuals recruited from university students and employees of the hospital were studied. The frequency of CYP21A2 mutated alleles in our sample was 15.3% (77.3% were mild mutations, 9% were severe mutations and 13.6% were novel variants). Gene dosage assessment was also performed when CYP21A2 gene duplication was suspected. This analysis showed that 7% of individuals bore a chromosome with a duplicated CYP21A2 gene, where one of the copies was mutated. CONCLUSIONS: As far as we know, the present study has shown the highest frequency of 21OHD carriers reported by a genotyping analysis. In addition, a high frequency of alleles with CYP21A2 duplications, which could be misinterpreted as 21OHD alleles, was found. Moreover, a high frequency of novel genetic variations with an unknown effect on 21-hydroxylase activity was also found. The high frequency of gene duplications, as well as novel variations, should be considered since they have an important involvement in carrier testing and genetic counseling

RocA Binds CsrS To Modulate CsrRS-Mediated Gene Regulation in Group A Streptococcus

Bacterial two-component regulatory systems, comprising a membrane-bound sensor kinase and cytosolic response regulator, are critical in coordinating the bacterial response to changing environmental conditions. More recently, auxiliary regulators which act to modulate the activity of two-component systems, allowing integration of multiple signals and fine-tuning of bacterial responses, have been identified. RocA is a regulatory protein encoded by all serotypes of the important human pathogen group A Streptococcus. Although RocA is known to exert its regulatory activity via the streptococcal two-component regulatory system CsrRS, the mechanism by which it functions was unknown. Based on new experimental evidence, we propose a model whereby RocA interacts with CsrS in the streptococcal cell membrane to enhance CsrS autokinase activity and subsequent phosphotransfer to the response regulator CsrR, which mediates transcriptional repression of target genes.The orphan regulator RocA plays a critical role in the colonization and pathogenesis of the obligate human pathogen group A Streptococcus. Despite multiple lines of evidence supporting a role for RocA as an auxiliary regulator of the control of virulence two-component regulatory system CsrRS (or CovRS), the mechanism of action of RocA remains unknown. Using a combination of in vitro and in vivo techniques, we now find that RocA interacts with CsrS in the streptococcal membrane via its N-terminal region, which contains seven transmembrane domains. This interaction is essential for RocA-mediated regulation of CsrRS function. Furthermore, we demonstrate that RocA forms homodimers via its cytoplasmic domain. The serotype-specific RocA truncation in M3 isolates alters this homotypic interaction, resulting in protein aggregation and impairment of RocA-mediated regulation. Taken together, our findings provide insight into the molecular requirements for functional interaction of RocA with CsrS to modulate CsrRS-mediated gene regulation

Dinâmica da vegetação da região de Humaitá - AM durante o Pleistoceno tardio e o Holoceno

Vegetation dynamics of Western Amazonia during the past 42000 cal yr BP was studied by pollen, sedimentary facies, 14C dating δ13C and C/N. Two sediment cores were sampled from Humaitá in southern Amazonas state, and Porto Velho, northern Rondônia. These sites, located in western Brazilian Amazonia, are covered by grassland and tropical rainforest vegetation, respectively. The sedimentary deposits are predominantly composed of massive sand, heterolithic mud/sand, and laminated or massive mud representative of sediment accumulation in floodplain, active channel, abandoned channel, and oxbow lake sedimentary environments. In these settings, reducing and low energy subaqueous conditions were developed, locally favoring preservation of a pollen community of herbaceous vegetation and glacial forest represented mainly by Alnus, Drymis, Hedyosmum, Podocarpus, and Weinmannia trees at least between > 42,033 – 43,168 cal yr BP and <34,804 – 35,584 cal yr BP. The herbaceous and arboreal vegetation ecotone persisted from the early to mid-Holocene, whilst the cold pollen assemblage became extinct. In this work, we record a significant plant population, at present restricted to Andean areas located at altitudes higher than 2000 - 3000 m, in areas of the Amazonia lowland toward the onset of the Last Glacial Maximum. This suggests that this time interval might have seen temperatures lower than previously proposed for this region.CNPq - Conselho Nacional de Desenvolvimento Científico e TecnológicoCAPES - Coordenação de Aperfeiçoamento de Pessoal de Nível SuperiorA dinâmica da vegetação oeste da Amazônia durante os últimos 42000 anos AP foi estudada por pólen, fácies sedimentares, datação por 14C, δ13C e C/N. Dois testemunhos foram coletados, o primeiro próximo da cidade de Humaitá no sul do Estado do Amazonas e o segundo nas proximidades de Porto velho, norte de Rondônia. Os pontos de amostragem estão localizados em uma região coberta por campos naturais e vegetação de floresta tropical, respectivamente. Os sedimentos depositados são predominantemente compostos por areia compacta, lama e areia com estratificação heterolítica, lama laminada e compacta representando sedimentos acumulados em um canal ativo, planície aluvial e lago em ferradura representando os ambientes sedimentares. Nessa configuração, as condições subaquáticas são desenvolvidas em um ambiente de baixa energia, favorecendo localmente a preservação da comunidade de grãos de pólen de vegetação herbácea e de floresta glacial representado principalmente por Alnus, Drymis, Hedyosmum, Podocarpus e Weinmannia com ocorrência entre > 42.033 – 43.168 cal anos AP e 34.804 – 35.584 cal anos AP. A vegetação arbórea e herbácea formam um ecótono que persiste do Holoceno Inferior ao Médio, enquanto a assembleia de vegetação adaptada ao frio se extingue. Os resultados desse trabalho sugerem a presença de uma significativa população de plantas de origem glacial nas planícies baixas do leste da Amazônia antes do Máximo Glacial Pleistocênico, as quais, na atualidade estão restritas aos Andes (2000-3000 m), sugerindo que nesse intervalo de tempo podem ter ocorrido temperaturas com valores inferiores aos que foram propostos para essa região