RESUMO

The assertion made by Wu et al. that aromaticity may have considerable implications for molecular design motivated us to use nucleus-independent chemical shifts (NICS) as an aromaticity criterion to evaluate the antifungal activity of two series of indol-4-ones. A linear regression analysis of NICS and antifungal activity showed that both tested variables were significantly related (p < 0.05); when aromaticity increased, the antifungal activity decreased for series I and increased for series II. To verify the validity of the obtained equations, a new set of 44 benzofuran-4-ones was designed by replacing the nitrogen atom of the five-membered ring with oxygen in indol-4-ones. The NICS(0) and NICS(1) of benzofuran-4-ones were calculated and used to predict their biological activities using the previous equations. A set of 10 benzofuran-4-ones was synthesized and tested in eight human pathogenic fungi, showing the validity of the equations. The minimum inhibitory concentration (MIC) in yeasts was 31.25 µg·mL-1 for Candida glabrata, Candida krusei and Candida guilliermondii with compounds 15-32, 15-15 and 15-1. The MIC for filamentous fungi was 1.95 µg·mL-1 for Aspergillus niger for compounds 15-1, 15-33 and 15-34. The results obtained support the use of NICS in the molecular design of compounds with antifungal activity.

Assuntos

Antifúngicos/farmacologia , Benzofuranos/farmacologia , Fungos/efeitos dos fármacos , Antifúngicos/química , Aspergillus niger/efeitos dos fármacos , Aspergillus niger/patogenicidade , Benzofuranos/química , Candida/efeitos dos fármacos , Candida/patogenicidade , Humanos , Testes de Sensibilidade Microbiana , Estrutura Molecular , Pichia/efeitos dos fármacos , Pichia/patogenicidade , Hidrocarbonetos Policíclicos Aromáticos/química , Hidrocarbonetos Policíclicos Aromáticos/farmacologia

RESUMO

The shielding cone concept is one of the most characteristic aspects of planar aromatic species. Herein, we explored how two neighbor aromatic moieties behave as dual planar-planar, planar-spherical, and spherical-spherical species given by biphenyl, [PhCB11 H11 ]- , and [CB11 H11 ]2 2- , respectively. Our results show two separate aromatic regimes given by Clar's sextet and spherical aromatic states, with independent shielding cones sharing shielding regions of moderate strength, which can be extended for networks involving multiple independent aromatic states.

RESUMO

After more than 20 years of use of preimplantation genetic tests for aneuploidies (PGS/PGT-A) there are still many problems related to the efficiency of this technique, most of them still without an adequate solution (Gleicher et al., 2018; Homer, 2019). From the clinical point of view, the benefits attributed to invasive PGT-A in the selection of euploid embryos remain controversial, especially due to the lack of scientific proof of its effectiveness in increasing live birth rates in various clinical situations, such as patients with advanced age, repeated implantation failures or recurrent miscarriages. In addition, evidence-based medicine also severely criticizes the rare randomized trials analyzing the clinical use of invasive PGT-A (Orvieto, 2016). If these criticisms were not enough, and undoubtedly one of the most important, it would be difficult to accurately assess the presence of embryonic mosaicism creating significant levels of false positive results, and worse, causing a real possibility of discarding healthy embryos. This makes the clinical application of PGT-A as a risky approach (Munné et al., 2017; Spinella et al., 2018). Another problem, not less important, would be the obligation to perform PGT-A by experienced embryologists, since otherwise the embryonic loss due to biopsy would be a frequent fact, something usually estimated below 10% but in some laboratories it may reach up to 30% of biopsied embryos (Munné, 2018). On the other hand, there are doubts about the future risks of invasive action of the usually 5-10 cell removed during biopsy for genetic diagnosis. Would there be repercussions for the health of these children? In animals, there are data suggesting that embryonic biopsies could be linked to changes in fetal neural tube or adrenal development (Wu et al., 2014; Zeng et al., 2013). Recently, Xu et al. (2016) described noninvasive chromosomal screening (NICS) by obtaining and sequencing free DNA dripped by embryos in the culture medium (without the need of embryo biopsy) creating a new non-aggressive and elegant perspective to preimplantation genetic diagnosis.

Assuntos

Testes Genéticos/métodos , Diagnóstico Pré-Implantação/métodos , Técnicas de Reprodução Assistida , Técnicas de Cultura Embrionária , Feminino , Humanos , Gravidez

RESUMO

This paper presents a theoretical study of the effects of substituents (F, Cl, Br, CH3, and CN) on the aromaticity of borazine (B3N3H6), using density functional theory (DFT) and the Hartree-Fock (HF) method. The calculations to optimize the geometries, structural properties, and vibrational frequencies were performed using the same 6-311G(d,p) and 6-311++G(d,p) basis sets, comparing the methods with experimental results. In the analysis of the NICSZZ values, it was found that that replacing the hydrogen atoms by halogen atoms (F, Cl, and Br) and CH3 reduced the aromaticity of the borazine molecule, while use of the CN group resulted in NICSZZ values (0.9-2.0 Å) very close to those of borazine, presenting the following order of increasing aromaticity: B3N3H3-(Br)3 < B3N3H3-(Cl)3 < B3N3H3-(F)3 < B3N3H3-(CH3)3 < B3N3H6 ~ B3N3H3-(CN)3. All the spectra of the compounds showed only the presence of transition peaks distant from the UV region, reflecting the large energy difference between the HOMO and LUMO orbitals. After the substitution of the borazine ring, all the compounds presented an intensification of the spectrum, with a shift of the maximum absorbance toward red, indicative of a bathochromic effect. There was a direct inverse relation between the energy gap and the maximum wavelength of the compounds.

RESUMO

Although there are a multitude of aromaticity indexes, only a few have a widespread usage. All famous aromaticity indexes are limited: HOMA and FLU are reference-dependent; ELF is π-bond-dependent; PDI is structurally dependent and NICS is ring size dependent. These limitations stimulate the continuous search for better (i.e., having no dependency), more flexible (i.e., applied to any aromatic system) and more effective (i.e., with excellent correlations with other indexes) aromaticity indexes. The D3BIA was our first topological aromaticity index. It is flexible, reference-independent and effective for planar and caged aromatic molecules. However, one of its terms, the degree of degeneracy (δ), is arbitrary and difficult to carry out for new users. Thus, in this work, we show that D2BIA-an improved version of D3BIA-is a good candidate to be used widely, since it retains the strong points of D3BIA while avoiding its weak point. In particular cases where all studied systems have δ = 1 (e.g., for acenes), then D2BIA equals D3BIA. For our recent study with acenes, D3BIA (and, as a consequence, D2BIA) has (have) an excellent correlation with FLU according to the MP3 method. In this work, by using DFT calculations for a series involving several six-membered and five-membered heteroaromatic rings, only D2BIA and NICS have very good correlation. All other well known aromaticity indexes used in this work (FLU, HOMA and ELF) gave poor correlations. As to homoaromatic systems, only D2BIA vs NICS and D2BIA vs FLU plots have excellent correlations. HOMA has the worst results in this series. Thus, D2BIA proved to be flexible and effective for the analysis of heteroaromatic rings of different sizes and for caged homoaromatic systems. Moreover, D2BIA has better correlations than D3BIA for planar aromatic systems, and same correlations for caged-homoaromatic systems. Graphical abstract D2BIA-an effective and improved version of the D3BIA aromaticity index.

RESUMO

In this work, the spectroscopic information, stability and aromaticity of the boron-nitrogen azulene and naphthalene molecules are provided by the use of CC2 (geometry optimization, dipole moment, UV-vis spectrum calculations) and DFT (vibrational spectrum and NMR calculations) methodologies. One isomer of the investigated boron-nitrogen naphthalene (boroazanaphthalene) and two isomers of boron-nitrogen azulene, 1,3,4,6,8-pentaaza-2,3a,5,7,8a-pentaboraazulene (BN-azulene) and 2,3a,5,7,8a-pentaaza-1,3,4,6,8- pentaboraazulene (NB-azulene), are stable systems. However, these molecules have different properties, i.e., different stability, dipole moment, and aromaticity based on the NICS approach. BN-naphthalene has a high dipole moment magnitude showing high polar character, while naphthalene is apolar. BN- and NB-azulene are weakly polar, while ordinary azulene is highly polar in character. Also, substitution of C atoms by B and N atoms decreases the aromaticity. In the case of NB-azulene, the seven-membered ring has anti-aromaticity behavior while both rings of BN-azulene exhibit aromaticity. We expect that the new theoretical data provided in this work will be useful in identifying and characterizing experimentally the compounds investigated, and in helping our understanding of the chemistry of boron-nitrogen molecules. Graphical abstract Boron-nitrogen alternating analogs of azulene. Spectral distinction between isomers.