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1.
Chemistry ; : e202403572, 2024 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-39365977

RESUMO

The presence of a guanine quadruplex in the opening reading frame of the messenger RNA coding for the transmembrane serine protease 2 (TMPRSS2) may pave the way to original anticancer and host-oriented antiviral strategy. Indeed, TMPRSS2 in addition to being overexpressed in different cancer types, is also related to the infection of respiratory viruses, including SARS-CoV-2, by promoting the cellular and viral membrane fusion through its proteolytic activity. The design of selective ligands targeting TMPRSS2 messenger RNA requires a detailed knowledge, at atomic level, of its structure. Therefore, we have used an original experimental-computational protocol to predict the first resolved structure of the parallel guanine quadruplex secondary structure in the RNA of TMPRSS2, which shows a rigid core flanked by a flexible loop. This represents the first atomic scale structure of the guanine quadruplex structure present in TMPRSS2 messenger RNA.

2.
Chirality ; 36(1): e23608, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37424264

RESUMO

In this work, we synthesized a family of three structurally related chiral oligothiophenes containing a 1,4-diketo-3,6-diarylpyrrolo[3,4-c]pyrrole (DPP) unit as the central core; functionalized with the same (S)-3,7-dimethyl-1-octyl chains on the nitrogen atoms of lactam moieties, they only differ in the number of lateral thiophene units. The aggregation modes of these π-conjugated chiral systems were evaluated by means of UV-Vis absorption and ECD spectroscopies in conditions of solution aggregation (CHCl3 /MeOH mixtures) and as thin films, describing in particular the impact of the π-conjugation length on the chiroptical properties. Interestingly, we found that the variable number of thiophene units attached to the DPP core affects not only the propensity to aggregation but also the aggregates' helicity. ECD revealed information about the supramolecular arrangement of these molecules, that one would not obtain by using conventional optical spectroscopy and microscopy techniques. Thin film samples revealed very different aggregation modes with respect to solution aggregates, casting doubts on the common assumption that these latter may serve as simple models of the former ones.

3.
Chirality ; 36(5): e23668, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38747133

RESUMO

The absolute configuration of three chiral eugenol derivatives was assigned by a multi-step methodology based on enantioselective HPLC combined with spectroscopic and theoretical calculations. Milligram amounts of enantiopure forms used for stereochemical characterization were isolated by HPLC on the immobilized amylose-based chiral stationary phase Chiralpak IG using normal phase elution conditions. The absolute configuration was indirectly determined for one of the three compounds by 1H NMR via methoxy-α-trifluoromethyl-α-phenylacetic acid derivatization (Mosher's acid). Comparison of the experimental and predicted electronic circular dichroism spectra confirmed the stereochemical assignment by Mosher's method and extended the absolute configuration assignment to two other chiral compounds.

4.
Chem Biodivers ; 21(4): e202400256, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38361228

RESUMO

The plant species, Sonchus wightianus DC., was historically used in China for both medicinal and dietary uses. In present study, seven new guaiane sesquiterpenoids (1-7) and one cytochalasin (8), along with five known guaianes (9-13) and two known cytochalasins (14 and 15), were isolated from the whole plants of S. wightianus. These guaianes showed structural variations in the substituents at C-8 and/or C-15, and compounds 6 and 7 are two sesquiterpenoid glycoside derivatives. Their structures were determined by extensive analysis of spectroscopic, electronic circular dichroism, and X-ray diffraction data, and chemical method. Biological tests revealed that compounds 5 and 8 are potent and selective immunosuppressive reagents.


Assuntos
Sesquiterpenos , Sonchus , Citocalasinas/química , Sesquiterpenos/farmacologia , Sesquiterpenos/química , Difração de Raios X , China , Estrutura Molecular
5.
Int J Mol Sci ; 25(12)2024 Jun 12.
Artigo em Inglês | MEDLINE | ID: mdl-38928181

RESUMO

A simplified molecular-dynamics-based electronic circular dichroism (ECD) approach was tested on three condensed derivatives with limited conformational flexibility and an isochroman-2H-chromene hybrid, the ECD spectra of which could not be precisely reproduced by the conventional ECD calculation protocol. Application of explicit solvent molecules at the molecular mechanics (MD) level in the dynamics simulations and subsequent TDDFT-ECD calculation for the unoptimized MD structures was able to improve the agreements between experimental and computed spectra. Since enhancements were achieved even for molecules with limited conformational flexibility, deformations caused by the solvent molecules and multitudes of conformers produced with unoptimized geometries seem to be key factors for better agreement. The MD approach could confirm that aggregation of the phenanthrene natural product luzulin A had a significant contribution to a specific wavelength range of the experimental ECD. The MD approach has proved that dimer formation occurred in solution and this was responsible for the anomalous ECD spectrum. The scope and limitations of the method have also been discussed.


Assuntos
Dicroísmo Circular , Simulação de Dinâmica Molecular , Dicroísmo Circular/métodos , Fenantrenos/química , Conformação Molecular , Solventes/química
6.
Molecules ; 29(19)2024 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-39407639

RESUMO

In this study, four previously undescribed flavonoids, named epimesatines P (1), Q (2), R (3), and S (4), were isolated from the aerial parts of Epimedium sagittatum Maxim. Their structures and absolute configurations were confirmed via spectroscopic analyses, quantum chemical electronic circular dichroism (ECD) calculations, Mo2(OAc)4-induced ECD, and Rh2(OCOCF3)4-induced ECD experiments. Epimesatines Q and R were characterized by the presence of furan rings. A cytotoxicity assay demonstrated that epimesatines P-S exhibited significant inhibitory effects on the viability of MCF-7 human breast cancer cells, with IC50 values ranging from 1.27 to 50.3 µM. Notably, epimesatines Q and R exhibited superior efficacy against MCF-7 cells compared to epimesatines P and S, suggesting that the presence of furan rings may enhance their activity against MCF-7 cells. Specifically, epimesatine Q displayed a more potent inhibitory effect at 1.27 µM compared to a positive control, docetaxel, which had an IC50 of 2.13 µM, highlighting its potential as a therapeutic agent for breast cancer. Importantly, none of the tested compounds exhibited obvious toxicity toward MCF-10A human breast epithelial cells. Furthermore, compounds 1, 3, and 4 were found to significantly inhibit the expression of sphingosine kinase 1 (Sphk1) in MCF-7 cells.


Assuntos
Epimedium , Flavonoides , Humanos , Epimedium/química , Flavonoides/farmacologia , Flavonoides/química , Flavonoides/isolamento & purificação , Células MCF-7 , Antineoplásicos Fitogênicos/farmacologia , Antineoplásicos Fitogênicos/química , Antineoplásicos Fitogênicos/isolamento & purificação , Estrutura Molecular , Sobrevivência Celular/efeitos dos fármacos
7.
Angew Chem Int Ed Engl ; : e202414490, 2024 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-39286924

RESUMO

Very recently, the control of dynamic chirality has emerged as a powerful strategy to design chiral functional materials. In this context, we describe herein a molecular design in which a tethered configurationally stable binaphthyl chiral unit efficiently controls the dynamic chirality of donor-acceptor fluorophores, involving diverse indolocarbazoles as electron donors and terephthalonitrile as an electron acceptor. The high conformational discrimination in such a molecular system suggested by density functional theory calculations is experimentally probed using electronic and vibrational circular dichroism and confirmed by the crystallization of these chiral molecules in gel and their single crystal X-ray diffraction analysis. In addition to extending the scope of dynamic chirality control to donor-acceptor fluorophores, this work also highlights the positive effect of the configurationally stable chiral inductor on the magnitude of the dissymmetry factors of the active dynamically chiral fluorophores, both in ground and excited states, through chiral perturbation.

8.
J Comput Chem ; 44(4): 626-643, 2023 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-36380723

RESUMO

We introduce FCclasses3, a code to carry out vibronic simulations of electronic spectra and nonradiative rates, based on the harmonic approximation. Key new features are: implementation of the full family of vertical and adiabatic harmonic models, vibrational analysis in curvilinear coordinates, extension to several electronic spectroscopies and implementation of time-dependent approaches. The use of curvilinear valence internal coordinates allows the adoption of quadratic model potential energy surfaces (PES) of the initial and final states expanded at arbitrary configurations. Moreover, the implementation of suitable projectors provides a robust framework for defining reduced-dimensionality models by sorting flexible coordinates out of the harmonic subset, so that they can then be treated at anharmonic level, or with mixed quantum classical approaches. A set of tools to facilitate input preparation and output analysis is also provided. We show the program at work in the simulation of different spectra (one and two-photon absorption, emission and resonance Raman) and internal conversion rate of a typical rigid molecule, anthracene. Then, we focus on absorption and emission spectra of a series of flexible polyphenyl molecules, highlighting the relevance of some of the newly implemented features. The code is freely available at http://www.iccom.cnr.it/en/fcclasses/.

9.
Chemistry ; 29(62): e202301982, 2023 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-37515814

RESUMO

Instrumental techniques able to identify and structurally characterize the aggregation states in thin films of chiral organic π-conjugated materials, from the first-order supramolecular arrangement up to the microscopic and mesoscopic scale, are very helpful for clarifying structure-property relationships. Chiroptical imaging is currently gaining a central role, for its ability of mapping local supramolecular structures in thin films. The present review gives an overview of electronic circular dichroism imaging (ECDi), circularly polarized luminescence imaging (CPLi), and vibrational circular dichroism imaging (VCDi), with a focus on their applications on thin films of chiral organic dyes as case studies.

10.
Chirality ; 35(11): 796-804, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37161511

RESUMO

In this paper, we describe the synthesis and the (chir)optical properties of a novel series of circularly polarized luminescent emitters. These molecules involve a compact single benzene-based donor-acceptor fluorophore composed of two cyclic alkylamines as electron donors and a phthalonitrile moiety as electron acceptor linked to a configurationally stable BINOL acting as a chiral perturbation unit. These new compounds display fair quantum yields (up to 66%) with emission maxima around 500 nm in toluene solutions, and the study of their chiroptical properties has shown that the cyclic alkylamine's ring size affects significantly the luminescence dissymmetry factors, reaching 2.2 × 10-3 for the larger cyclic alkylamine moieties.

11.
Chem Biodivers ; 20(6): e202300319, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37183173

RESUMO

Sphaeranthus africanus L. is native in Vietnam. Little is known about α-glucosidase inhibition of Sphaeranthus africanus and its isolated compounds. A bioactive-guided isolation was applied to the Vietnamese Sphaeranthus africanus to find α-glucosidase inhibitory components. Eight compounds were detected and structurally elucidated. They are 3-angeloyloxy-5-[2'',3''-epoxy-2''-methylbutanoyloxy]-7-hydroxycarvotacetone, 3-angeloyloxy-5-[3''-chloro-2''-hydroxy-2''-methylbutanoyloxy]-7-hydroxycarvotacetone, 3-angeloyloxy-5-[2''R,3''R-dihydroxy-2''-methyl-butanoyloxy]-7-hydroxycarvotacetone, 3-angeloyloxy-5-[2''S,3''R-dihydroxy-2''-methylbutanoyloxy]-7-hydroxycarvotacetone, 3-angeloyloxy-5-[2''S,3''S-dihydroxy-2''-methylbutanoyloxy]-7-hydroxycarvotacetone, 5-angeloyloxy-7-hydroxy-3-tigloyloxycarvotacetone, 3-O-methylquercetin, and chrysosplenol D. Their chemical structures were elucidated by extensive 1D and 2D NMR analysis and high-resolution mass spectroscopy as well as comparisons in literature. 3-Angeloyloxy-5-[2''S,3''S-dihydroxy-2''-methylbutanoyloxy]-7-hydroxycarvotacetone is a new compound. Isolated compounds were evaluated for the α-glucosidase inhibition. Isolated compounds showed moderate activity with IC50 values ranging from 128.9-274.3 µM while others are weak. A molecular docking study was conducted, indicating that isolated compounds are potent α-glucosidase inhibitory compounds.


Assuntos
Asteraceae , Extratos Vegetais , Extratos Vegetais/química , Simulação de Acoplamento Molecular , alfa-Glucosidases , Asteraceae/química , Componentes Aéreos da Planta/química , Estrutura Molecular
12.
Molecules ; 28(6)2023 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-36985544

RESUMO

Two transition metal complexes were synthesized with Ni(II) and Cu(II) using a tetradentate Schiff-base ligand, (R,R) and (S,S)-N,N'-Bis(3,5-di-tert-butylsalicylidene)-1,2-cyclohexanediamine. The stereochemical properties of the ligand and the metal complexes were investigated using a combined experimental and theoretical approach. Multiple spectroscopic techniques, which include IR, vibrational circular dichroism (VCD), UV-Vis and electronic circular dichroism (ECD), as well as Raman and the newly discovered ECD-circularly polarized Raman (i.e., eCP-Raman) spectroscopies were utilized. The good agreement achieved between the experimental and simulated IR, VCD, UV-Vis and ECD spectra of the ligand allowed one to identify the presence of three main ligand conformers in solution, thanks, especially to the high VCD sensitivity to the conformations associated with the tertbutyl groups. The helicity of the metal complexes was identified to be M and P for those with the (R,R) and (S,S) ligands, respectively. Furthermore, eCP-Raman measurements were carried out for the two metal complexes under (near) resonance. Their induced solvent chiral Raman features were explained, and the potential application of eCP-Raman was discussed.

13.
Molecules ; 28(8)2023 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-37110825

RESUMO

The electronic circular dichroism (ECD) spectra of aqueous d-glucose and d-galactose were modeled using a theoretical-computational approach combining molecular dynamics (MD) simulations and perturbed matrix method (PMM) calculations, hereafter termed MD-PMM. The experimental spectra were reproduced with a satisfactory accuracy, confirming the good performances of MD-PMM in modeling different spectral features in complex atomic-molecular systems, as already reported in previous studies. The underlying strategy of the method was to perform a preliminary long timescale MD simulation of the chromophore followed by the extraction of the relevant conformations through essential dynamics analysis. On this (limited) number of relevant conformations, the ECD spectrum was calculated via the PMM approach. This study showed that MD-PMM was able to reproduce the essential features of the ECD spectrum (i.e., the position, the intensity, and the shape of the bands) of d-glucose and d-galactose while avoiding the rather computationally expensive aspects, which were demonstrated to be important for the final outcome, such as (i) the use of a large number of chromophore conformations; (ii) the inclusion of quantum vibronic coupling; and (iii) the inclusion of explicit solvent molecules interacting with the chromophore atoms within the chromophore itself (e.g., via hydrogen bonds).

14.
Molecules ; 28(5)2023 Feb 24.
Artigo em Inglês | MEDLINE | ID: mdl-36903367

RESUMO

Synthetic cathinones, such as 3,4-methylenedioxypyrovalerone (MDPV), are widely abused due to their psychostimulant effects. As they are chiral molecules, studies of their stereochemical stability (racemization can occur in certain temperatures and acidic/basic environments) and of their biological and/or toxicity effects (enantiomers might display different properties) are of great relevance. In this study, the liquid chromatography (LC) semi-preparative enantioresolution of MDPV was optimized to collect both enantiomers with high recovery rates and enantiomeric ratio (e.r.) values. The absolute configuration of the MDPV enantiomers was determined by electronic circular dichroism (ECD) with the aid of theoretical calculations. The first eluted enantiomer was identified as S-(-)-MDPV and the second eluted enantiomer was identified as R-(+)-MDPV. A racemization study was performed by LC-UV, showing enantiomers' stability up to 48 h at room temperature and 24 h at 37 °C. Racemization was only affected by higher temperatures. The potential enantioselectivity of MDPV in cytotoxicity and in the expression of neuroplasticity-involved proteins-brain-derived neurotrophic factor (BDNF) and cyclin-dependent kinase 5 (Cdk5)-was also evaluated using SH-SY5Y neuroblastoma cells. No enantioselectivity was observed.


Assuntos
Estimulantes do Sistema Nervoso Central , Neuroblastoma , Humanos , Catinona Sintética , Estereoisomerismo , Cromatografia Líquida , Pirrolidinas/química , Benzodioxóis/química
15.
Angew Chem Int Ed Engl ; 62(29): e202304075, 2023 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-37158668

RESUMO

A chiral bispyrene macrocycle designed for exclusive intermolecular excimer fluorescence upon aggregation was synthesized by a double hydrothiolation of a bis-enol ether macrocycle followed by intramolecular oxidation of free thiols. Unusually high stereoselectivity was achieved for the thiol-ene additions under templated conditions and Et3 B/O2 radical initiation. After enantiomer separation (chiral stationary phase HPLC), aqueous conditions provoked aggregation. Detailed structural evolution was afforded by ECD/CPL monitoring. Three regimes can be observed and characterized by strong modifications in chiroptical patterns under, at, or above a 70 % H2 O : THF threshold. In luminescence, high glum dissymmetry factors values were obtained, up to 0.022, as well as a double sign inversion of CPL signals during the aggregation, a behavior rationalized by time-dependent density functional theory (TDDFT) calculations. Langmuir layers of enantiopure disulfide macrocycles were formed at the air-water interface and transferred onto solid substrates to afford Langmuir-Blodgett films, which were then studied by AFM and UV/ECD/fluorescence/CPL.

16.
Chemistry ; 28(20): e202104302, 2022 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-35030280

RESUMO

This Concept article summarizes recent work on the development of a new form of chiral Raman spectroscopy, eCP-Raman, which combines two spectroscopies: electronic circular dichroism (ECD) and circularly polarized Raman (CP-Raman). First, some puzzling observations while carrying out Raman optical activity (ROA) measurements of several transition metal complexes under resonance are described, as well as the search for the mechanisms responsible. Then an equation for quantifying the eCP-Raman contribution is presented, followed by several examples of how eCP-Raman influences the IR -IL spectra of achiral and chiral solvent molecules and of a number of chiral solutes under resonance. The conditions to extract resonance ROA, when the eCP-Raman contribution is minimized, are also discussed. Finally, we comment on the potential applications of eCP-Raman.

17.
Chemistry ; 28(51): e202201178, 2022 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-35674127

RESUMO

The chiroptical features of chiral diketopyrrolo[3,4-c]pyrrole (DPP) derivatives have been only marginally investigated to date. In this regard, we have synthesized ad hoc four chiral DPP dyes, functionalized with enantiopure alkyl groups from natural sources either on the lactam moieties or on the terminal positions of the π-conjugated backbone, to promote an efficient self-assembly into chiral supramolecular structures. For each of them, the aggregation modes has been investigated by absorbance and ECD spectroscopies in conditions of solution aggregation and on thin films, considering the effects of deposition technique (drop casting vs. spin coating) and post-deposition operations (solvent and thermal annealing). The effect of the structure of lateral π-conjugated units attached to the central DPP scaffold, as well as that of the position of the alkyl chiral group, has been assessed. ECD revealed superior capability, compared to absorbance spectroscopy, to provide information on the aggregation modes and to detect the possible co-existence of multiple aggregation pathways.

18.
Anal Bioanal Chem ; 414(22): 6695-6705, 2022 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-35869992

RESUMO

Unambiguous identification of the components of a natural mixture remains a challenging and meticulous issue. Usually, different analytical techniques and laborious separation protocols are employed; nevertheless, in some cases, delicate and equivocal problems are hardly addressed by traditional methods. In this context, an original methodology for the analysis of natural samples consisting of recent mass spectrometry methods based on ion mobility (MS-IM) is proposed. As an example, a polar fraction obtained by the essential oil prepared from Senecio transiens, an endemic plant harvested on the Corsica Island, was selected for this study to show how IM-MS-based methods easily provide very useful insights suggesting the presence of two diastereomers. To unambiguously confirm this hypothesis and verify reliability of the IM-MS results, the purified compounds were further analysed by means of nuclear magnetic resonance (NMR) methodologies, allowing the structural elucidation and the identification of two new natural compounds, diastereomers of 4-acetoxy-5,9-dimethyl-3-(2-methylpropenyl)-2-oxabicyclo[4.4.0] dec-9-ene, reported here for the first time.


Assuntos
Óleos Voláteis , Senécio , Espectroscopia de Ressonância Magnética , Espectrometria de Massas/métodos , Óleos Voláteis/química , Reprodutibilidade dos Testes , Senécio/química
19.
Bioorg Chem ; 127: 106027, 2022 10.
Artigo em Inglês | MEDLINE | ID: mdl-35878451

RESUMO

A total of 33 structurally diverse isoquinoline alkaloids were isolated from the rhizomes of Menispermum dauricum, including seventeen benzylisoquinoline analogues (menisperdaurines A-Q, 1-17), five protoberberine analogues (menisperdaurines R-V, 18-22), a quaternary phenanthrene alkaloid (menisperdaurine W, 23) and ten known compounds (24-33). Compound structures, including absolute configurations, were determined by extensive spectroscopic methods, quantum chemical calculations of chemical shifts, and calculated and experimental electronic circular dichroism (ECD) data. Compounds 1-5 were glycosidic benzylisoquinolines with glucose moieties attached at the C-12 position. Compound 8 was the first example that was isolated from the rhizomes of Menispermum dauricum, benzylisoquinoline and an aromatic unit connected by a sugar bridge. Compounds were evaluated for their inhibitory effects on the dopamine D1 receptor. Compounds 1, 8, 21, 24 and 29 showed potent D1 antagonistic activities, with IC50 values ranging from 1.0 to 4.5 µM. Compound 1 exhibited the highest antagonistic activity with an IC50 value of 1.0 ± 0.2 µM.


Assuntos
Alcaloides , Benzilisoquinolinas , Menispermum , Alcaloides/química , Alcaloides/farmacologia , Isoquinolinas/farmacologia , Menispermum/química , Estrutura Molecular , Receptores de Dopamina D1
20.
Chirality ; 34(12): 1515-1525, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36300855

RESUMO

Hexahydrocurcumin (HHC) and octahydrocurcumin (OHC) were synthesized, and their enantiomers were separated using supercritical fluid chromatography. The absolute configurations (ACs) of HHC and OHC were independently determined using experimental measurements and quantum theoretical predictions of vibrational circular dichroism, electronic circular dichroism, and optical rotatory dispersion. These studies lead to AC assignments of (-)-(R)-HHC and (+)-(R,R)-OHC. The AC of OHC is further confirmed by its structure determined from single crystal x-ray diffraction.


Assuntos
Estereoisomerismo , Dispersão Óptica Rotatória , Dicroísmo Circular
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