Theoretical Study of the Thermolysis Reaction and Chemiexcitation of Coelenterazine Dioxetanes

Coelenterazine and other imidazopyrazinones are important bioluminescent substrates widespread in marine species and can be found in eight phyla of luminescent organisms. Light emission from these systems is caused by the formation and subsequent thermolysis of a dioxetanone intermediate, whose decomposition allows for efficient chemiexcitation to singlet excited states. Interestingly, some studies have also reported the involvement of unexpected dioxetane intermediates in the chemiand bioluminescent reactions of Coelenterazine, albeit with little information on the underlying mechanisms of these new species. Herein, we have employed a theoretical approach based on density functional theory to study for the first time the thermolysis reaction and chemiexcitation profile of two Coelenterazine dioxetanes. We have found that the thermolysis reactions of these species are feasible but with relevant energetic differences. More importantly, we found that the singlet chemiexcitation profiles of these dioxetanes are significantly less efficient than the corresponding dioxetanones. Furthermore, we identified triplet chemiexcitation pathways for the Coelenterazine dioxetanes. Given this, the chemiexcitation of these dioxetanes should lead only to minimal luminescence. Thus, our theoretical investigation of these systems indicates that the thermolysis of these dioxetanes should only provide dark pathways for the formation of nonluminescent degradation products of the chemi- and bioluminescent reactions of Coelenterazine and other imidazopyrazinones

Carbon dots from tryptophan doped glucose for peroxynitrite sensing

Tryptophan doped carbon dots (Trp-CD) were microwave synthesized. The optimum conditions of synthesizing of the Trp-CD were established by response surface multivariate optimization methodologies and were the following: 2.5 g of glucose and 300 mg of tryptophan diluted in 15 mL of water exposed for 5 min to a microwave radiation of 700 W. Trp-CD have an average size of 20 nm, were fluorescent with a quantum yield of 12.4% and the presence of peroxynitrite anion (ONOO−) provokes quenching of the fluorescence. The evaluated analytical methodology for ONOO− detection shows a linear response range from 5 to 25 μM with a limit of detection of 1.5 μM and quantification of 4.9 μM. The capability of the ONOO− quantification was evaluated in standard solutions and in fortified serum samples

Investigation of the Anticancer and Drug Combination Potential of Brominated Coelenteramines toward Breast and Prostate Cancer

Cancer is a very challenging disease to treat, both in terms of therapeutic efficiency and harmful side effects, which continues to motivate the pursuit for novel molecules with potential anticancer activity. Herein, we have designed, synthesized, and evaluated the cytotoxicity of different brominated coelenteramines, which are metabolic products and synthesis precursors of the chemi-/bioluminescent system of marine coelenterazine. The evaluation of the anticancer potential of these molecules was carried out for both prostate and breast cancer, while also exploring their potential for use in combination therapy. Our results provided further insight into the structure-activity relationship of this type of molecule, such as their high structural specificity, as well highlighting the 4-bromophenyl moiety as essential for the anticancer activity. The obtained data also indicated that, despite their similarity, the anticancer activity displayed by both brominated coelenteramines and coelenterazines should arise from independent mechanisms of action. Finally, one of the studied coelenteramines was able to improve the profile of a known chemotherapeutic agent, even at concentrations in which its anticancer activity was not relevant. Thus, our work showed the potential of different components of marine chemi-/bioluminescent systems as novel anticancer molecules, while providing useful information for future optimizations

Spatio-temporal study and population structure of Daptonema Oxycerca (Nematoda: Xyalidae) in Coroa Grande, Rio de Janeiro, Brazil

Daptonema oxycerca foi descrita originalmente para o Mar do Norte, mas até o momento nada se conhece sobre essa espécie em regiões tropicais. A distribuição espaço-temporal e a estrutura populacional de D. oxycerca foram estudadas durante o período de um ano (de Maio 1998 a Abril 1999) em Coroa Grande, Rio de Janeiro, Brasil. Para a amostragem, dois transectos fixos e perpendiculares à linha d'água foram estabelecidos, e, em cada transecto, quatro níveis foram marcados para representar as zonas superior e inferior do médiolitoral. As menores temperaturas foram observadas no final do inverno e início da primavera e as maiores temperaturas no verão. A densidade de D. oxycerca variou durante o ano, com um pico em agosto. Essa tendência foi observada para os machos, as fêmeas grávidas e as fêmeas não-grávidas. A densidade da espécie correlacionou-se negativamente com a temperatura. A variação da razão sexual não foi significativa. D. oxycerca foi mais abundante no nível superior do médiolitoral em ambos os transectos. Esse trabalho representa o primeiro registro de D. oxycerca no Brasil, assim como, confirma a influência da temperatura na regulação de sua densidade populacional.Daptonema oxycerca was originally described from the North Sea and, up to now, nothing is known of this species in tropical regions. The spatio-temporal distribution and the population structure of this species was studied during one-year period (from May 1998 through April 1999) in Coroa Grande, Rio de Janeiro, Brazil. For sampling, two fixed, parallel transects were established perpendicularly to the shoreline, and at each transect, four, equally spaced levels were marked to represent the upper and the low intertidal zones. The lowest temperatures occurred in the end of the austral winter and first month of the spring and the highest temperatures occurred in the austral summer. The density of D. oxycerca varied during the year, with a peak in August. This tendency was observed for males, ovigerous females, and non-ovigerous females. The species density was negative correlated with temperature. The sex ratio was not statistically significant. D. oxycerca was most abundant at the upper intertidal level in both transects. This work provides the first record of D. oxycerca in Brazil, and confirms the influence of temperature in regulating its population density

Tuning the Intramolecular Chemiexcitation of Neutral Dioxetanones by Interaction with Ionic Species

The intramolecular chemiexcitation of high-energy peroxide intermediates, such as dioxetanones, is an essential step in different chemi- and bioluminescent reactions. Here, we employed the Time-Dependent Density Functional Theory (TD-DFT) methodology to evaluate if and how external stimuli tune the intramolecular chemiexcitation of model dioxetanones. More specifically, we evaluated whether the strategic placement of ionic species near a neutral dioxetanone model could tune its thermolysis and chemiexcitation profile. We found that these ionic species allow for the “dark” catalysis of the thermolysis reaction by reducing the activation barrier to values low enough to be compatible with efficient chemi- and bioluminescent reactions. Furthermore, while the inclusion of these species negatively affected the chemiexcitation profile compared with neutral dioxetanones, these profiles appear to be at least as efficient as anionic dioxetanones. Thus, our results demonstrated that the intramolecular chemiexcitation of neutral dioxetanones can be tuned by external stimuli in such a way that their activation barriers are decreased. Thus, these results could help to reconcile findings that neutral dioxetanones could be responsible for efficient chemi-/bioluminescence, while being typically associated with high activation parameters

Qualidade de silagens de bagaço úmido de laranja e cama de frango e desempenho de novilhos Canchim.

A qualidade de silagens de bagaço de laranja e cama-de-frango com diferentes proporções (80:20; 60:40; 40:60 e 20:80) e de silagem pura de cama-de-frango com diferentes teores de matéria seca, obtidos pela utilização de diferentes proporções de água e cama-de-frango (0:100; 15:85; 30:70 e 45:55) foram avaliadas em silos de laboratório. Uma silagem com 45:55 de cama-de-frango e bagaço de laranja foi utilizada para teste de ganho de peso com animais Canchim. Houve incremento (P<0,05) na porcentagem de MS, PB, pH, FDN, , cinzas, amônia, Ca e P com o aumento da proporções de cama-de-frango em relação ao bagaço de laranja. A silagem com 15:85 apresentou maior teor de PB e menor teor de amônia que as silagens com 30:70 e 45:55. A dieta com silagem de bagaço de laranja e cama-de-frango, cana-de-açúcar e concentrado (44:36:20), na base seca, permitiu consumo adequado para ganho de peso de 1,39 kg por dia

Estrutura populacional de ovinos da raça Morada Nova.

Resumo: O Presente estudo teve como objetivo avaliar a situação de risco de 36 rebanhos de ovinos da raça Morada Nova no estado de Pernambuco, Paraíba, Rio Grande do Norte, Ceará e São Paulo, Brasil. Com está finalidade foi feito um levantamento do número de animais machos e fêmeas em reprodução dos 36 rebanhos avaliados e estimou-se número efetivo (Ne), taxa de consanguinidade (?F) e os valores de panmixia (PAM). Todos os rebanhos estudados apresentaram o Ne abaixo do valor mínimo estabelecido pela FAO (50) e a taxa de consanguinidade acima da média recomendada pela FAO (1%). Os resultados sugerem a necessidade de estabelecer um plano de gestão genética para todos os rebanhos, como forma de manutenção da variabilidade genética remanescente. Population structure of Morada Nova sheep breed. Abstract: The present study aimed to assess the risk status of flocks Morada Nova sheep breed. It was collected data from 36 herds located Pernambuco, Paraiba, Rio Grande do Norte, Ceará and São Paulo states, Brazil. It was used the number of males and females in reproduction of 36 herds and it was estimated effective number (Ne), inbreeding rate (?F) and the values of panmixia (PAM). All herds has Ne below the minimum established by the FAO (50) and the rate of inbreeding above the level recommended by FAO (1%). The results suggest the need to establish a management plan for all livestock genetics as a way of maintaining genetic variability

Comparative Investigation of the Chemiluminescent Properties of a Dibrominated Coelenterazine Analog

Chemi- and bioluminescence are remarkable light-emitting phenomena, in which thermal energy is converted into excitation energy due to a (bio)chemical reaction. Among a wide variety of chemi-/bioluminescent systems, one of the most well-known and studied systems is that of marine imidazopyrazinones, such as Coelenterazine and Cypridina luciferin. Due to the increasing usefulness of their chemi-/bioluminescent reactions in terms of imaging and sensing applications, among others, significant effort has been made over the years by researchers to develop new derivatives with enhanced properties. Herein, we report the synthesis and chemiluminescent characterization of a novel dibrominated Coelenterazine analog. This novel compound consistently showed superior luminescence, in terms of total light output and emission lifetime, to natural imidazopyrazinones and commercially available analogs in aprotic media, while being capable of yellow light emission. Finally, this new compound showed enhanced chemiluminescence in an aqueous solution when triggered by superoxide anion, showing potential to be used as a basis for optimized probes for reactive oxygen species. In conclusion, bromination of the imidazopyrazinone scaffold appears to be a suitable strategy for obtaining Coelenterazines with enhanced properties