Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 56
Filtrar
Mais filtros










Base de dados
Intervalo de ano de publicação
1.
Phys Chem Chem Phys ; 25(36): 24745-24760, 2023 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-37671434

RESUMO

To successfully understand and model the environmental fate of per- and polyfluoroalkyl substances (PFAS), it is necessary to know key physicochemical properties (PChPs) such as pKa; however, measured PChPs of PFAS are scarce and of uncertain reliability. In this study, quantitative structure-activity relationships (QSARs) were developed by correlating calculated (M062-X/aug-cc-pVDZ) vibrational frequencies (VF) and corresponding infrared intensities (IRInt) to the pKa of carboxylic acids, sulfonic acids, phosphonic acids, sulfonamides, betaines, and alcohols. Antisymmetric stretching VF of the anionic species were used for all subclasses except for alcohols where the OH stretching VF performed better. The individual QSARs predicted the pKa for each subclass mostly within 0.5 pKa units from the experimental values. The inclusion of IRInt as a pKa predictor for carboxylic acids improved the results by decreasing the root-mean-square error from 0.35 to 0.25 (n > 100). Application of the developed QSARs to estimate the pKa of PFAS within each subclass revealed that the length of the perfluoroalkyl chain has minimal effect on the pKa, consistent with other models but in stark contrast with the limited experimental data available.

2.
Int J Mol Sci ; 24(14)2023 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-37511119

RESUMO

One of the most significant factors for age-related macular degeneration (AMD) development is considered to be aging, the processes of which are closely associated with telomere shortening. The different forms, indicators of aggressiveness, and intensities of AMD can be observed in the same age group, confirming the need to find a biomarker for early diagnosis and be capable of monitoring the progression of the pathological process. Therefore, we investigated whether the relative telomere length (RTL) has any connection with the risk of development of disease and its progression. RTL was measured using RT-PCR in 166 people, including 96 patients with AMD. RTL was significantly lower in patients with AMD. Women were more likely to develop AMD than men (odds ratio (OR) = 9.53 × 106 vs. OR = 1.04 × 108, respectively). The decrease in RTL in patients reliably correlated with the progression of AMD, and the smallest RTL was observed in late-stage patients. RTL < 0.8 is a significant risk factor for disease progression. The results of our research showed that RTL may be considered as a potential biomarker and a promising predictor of disease progression in patients with early AMD.


Assuntos
Degeneração Macular , Telômero , Masculino , Humanos , Feminino , Telômero/genética , Envelhecimento/patologia , Fatores de Risco , Degeneração Macular/genética , Biomarcadores , Progressão da Doença
3.
Environ Toxicol Chem ; 42(11): 2317-2328, 2023 11.
Artigo em Inglês | MEDLINE | ID: mdl-37439660

RESUMO

Perfluoroalkyl carboxylic and sulfonic acids (PFCAs and PFSAs, respectively) have low acid dissociation constant values and are, therefore, deprotonated under most experimental and environmental conditions. Hence, the anionic species dominate their partitioning between water and organic phases, including octanol and phospholipid bilayers which are often used as model systems for environmental and biological matrices. However, data for solvent-water (SW) and membrane-water partition coefficients of the anion species are only available for a few per- and polyfluoroalkyl substances (PFAS). In the present study, an equation is derived using a Born-Haber cycle that relates the partition coefficients of the anions to those of the corresponding neutral species. It is shown via a thermodynamic analysis that for carboxylic acids (CAs), PFCAs, and PFSAs, the log of the solvent-water partition coefficient of the anion, log KSW (A- ), is linearly related to the log of the solvent-water partition coefficient of the neutral acid, log KSW (HA), with a unity slope and a solvent-dependent but solute-independent intercept within a PFAS (or CA) family. This finding provides a method for estimating the partition coefficients of PFCAs and PFSAs anions using the partition coefficients of the neutral species, which can be reliably predicted using quantum chemical methods. In addition, we have found that the neutral octanol-water partition coefficient, log KOW , is linearly correlated to the neutral membrane-water partition coefficient, log KMW ; therefore, log KOW , being a much easier property to estimate and/or measure, can be used to predict the neutral log KMW . Application of this approach to KOW and KMW for PFCAs and PFSAs demonstrates the utility of this methodology for evaluating reported experimental data and extending anion property data for chain lengths that are unavailable. Environ Toxicol Chem 2023;42:2317-2328. © 2023 SETAC.


Assuntos
Fluorocarbonos , Lipídeos de Membrana , Ácidos Sulfônicos , Solventes , Água/química , Ácidos Carboxílicos/análise , Octanóis , Ânions , Fluorocarbonos/química
4.
Int J Mol Sci ; 24(7)2023 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-37047717

RESUMO

One of the main causes of maternal and neonatal morbidity and mortality is pre-eclampsia. It is characterized by a high sFlt1/PlGF ratio, according to prior research. Pregestational diseases in mothers may increase the risk of developing pre-eclampsia. Only a few studies have looked at the connection between maternal comorbidities before conception and the sFlt1/PlGF ratio. The most recent information regarding the association between maternal pregestational diseases and the ratio of sFlt1/PlGF is described in this review. The paper also examines current research suggesting that changes in pregnancy hormones and metabolites are related to a high sFlt1/PlGF ratio. Certain maternal disorders have been found to dramatically raise sFlt-1 and sFlt1/PlGF levels, according to an analysis of the literature. There is still debate about the data on the association between the sFlt1/PlGF ratio and maternal disorders such as HIV, acute coronary syndromes, cardiovascular function in the mother between 19 and 23 weeks of pregnancy, thyroid hormones, diabetes, and cancer. Additional research is needed to confirm these findings.


Assuntos
Pré-Eclâmpsia , Gravidez , Feminino , Recém-Nascido , Humanos , Receptor 1 de Fatores de Crescimento do Endotélio Vascular , Fator de Crescimento Placentário , Fatores de Risco , Biomarcadores
5.
J Am Chem Soc ; 145(11): 6067-6078, 2023 03 22.
Artigo em Inglês | MEDLINE | ID: mdl-36881718

RESUMO

Described are ligand-directed catalysts for live-cell, photocatalytic activation of bioorthogonal chemistry. Catalytic groups are localized via a tethered ligand either to DNA or to tubulin, and red light (660 nm) photocatalysis is used to initiate a cascade of DHTz oxidation, intramolecular Diels-Alder reaction, and elimination to release phenolic compounds. Silarhodamine (SiR) dyes, more conventionally used as biological fluorophores, serve as photocatalysts that have high cytocompatibility and produce minimal singlet oxygen. Commercially available conjugates of Hoechst dye (SiR-H) and docetaxel (SiR-T) are used to localize SiR to the nucleus and microtubules, respectively. Computation was used to assist the design of a new class of redox-activated photocage to release either phenol or n-CA4, a microtubule-destabilizing agent. In model studies, uncaging is complete within 5 min using only 2 µM SiR and 40 µM photocage. In situ spectroscopic studies support a mechanism involving rapid intramolecular Diels-Alder reaction and a rate-determining elimination step. In cellular studies, this uncaging process is successful at low concentrations of both the photocage (25 nM) and the SiR-H dye (500 nM). Uncaging n-CA4 causes microtubule depolymerization and an accompanying reduction in cell area. Control studies demonstrate that SiR-H catalyzes uncaging inside the cell, and not in the extracellular environment. With SiR-T, the same dye serves as a photocatalyst and the fluorescent reporter for microtubule depolymerization, and with confocal microscopy, it was possible to visualize microtubule depolymerization in real time as the result of photocatalytic uncaging in live cells.


Assuntos
Corantes Fluorescentes , Luz , Ligantes , Corantes Fluorescentes/química , Microtúbulos , Reação de Cicloadição
6.
Int J Mol Sci ; 23(24)2022 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-36555727

RESUMO

The increasing frequency of isolation of methicillin-resistant Staphylococcus aureus (MRSA) limits the chances for the effective antibacterial therapy of staphylococcal diseases and results in the development of persistent infection such as bacteremia and osteomyelitis. The aim of this study was to identify features of the MRSAST239 0943-1505-2016 (SA943) genome that contribute to the formation of both acute and chronic musculoskeletal infections. The analysis was performed using comparative genomics data of the dominant epidemic S. aureus lineages, namely ST1, ST8, ST30, ST36, and ST239. The SA943 genome encodes proteins that provide resistance to the host's immune system, suppress immunological memory, and form biofilms. The molecular mechanisms of adaptation responsible for the development of persistent infection were as follows: amino acid substitution in PBP2 and PBP2a, providing resistance to ceftaroline; loss of a large part of prophage DNA and restoration of the nucleotide sequence of beta-hemolysin, that greatly facilitates the escape of phagocytosed bacteria from the phagosome and formation of biofilms; dysfunction of the AgrA system due to the presence of psm-mec and several amino acid substitutions in the AgrC; partial deletion of the nucleotide sequence in genomic island vSAß resulting in the loss of two proteases of Spl-operon; and deletion of SD repeats in the SdrE amino acid sequence.


Assuntos
Staphylococcus aureus Resistente à Meticilina , Infecções Estafilocócicas , Humanos , Staphylococcus aureus Resistente à Meticilina/genética , Staphylococcus aureus/genética , Infecção Persistente , Antibacterianos/farmacologia , Antibacterianos/uso terapêutico , Infecções Estafilocócicas/microbiologia , Testes de Sensibilidade Microbiana
7.
Int J Mol Sci ; 23(21)2022 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-36361738

RESUMO

Briefly, 25-hydroxyvitamin D (25(OH)D) plays an essential role in embryogenesis and the course of intra- and postnatal periods and is crucially involved in the functioning of the mother-placenta-fetus system. The low quantity of 25(OH)D during pregnancy can lead to an elevated risk for preeclampsia occurrence. Despite the numerous studies on the association of 25(OH)D deficiency and preeclampsia development, the current research on this theme is contradictory. In this review, we summarize and analyze study data on the effects of 25(OH)D deficiency and supplementation on pregnancy, labor, and fetal and neonatal outcomes.


Assuntos
Pré-Eclâmpsia , Complicações na Gravidez , Deficiência de Vitamina D , Gravidez , Recém-Nascido , Feminino , Humanos , Deficiência de Vitamina D/complicações , Vitamina D , Suplementos Nutricionais
8.
J Phys Chem A ; 126(48): 8976-8987, 2022 Dec 08.
Artigo em Inglês | MEDLINE | ID: mdl-36414392

RESUMO

Significant differences in the photochemical and photophysical behavior of trans-α-methylstilbene and trans-stilbene have been attributed to structural changes caused by the steric requirements of the methyl group. We present here the X-ray structures of cis- and trans-α-methylstilbene (c- and t-MeSt). This is the first X-ray structure of a cis-stilbene. Despite the pronounced departure from phenyl group coplanarity, the solid-state packing of t-MeSt resembles that of trans-stilbene in that both exhibit disorder with a bicycle pedal structural relationship, dynamic in t-St but static in t-MeSt. We compare the X-ray structures with calculated structures. We also compare our steady state and transient photochemical and spectroscopic results with predictions in a recent theoretical paper that anticipated some of our experiments. Deviations from planarity imposed by the methyl substitution account for the shorter lifetimes of the trans excited states. The rapid torsional relaxation of 1t-MeSt* to the twisted intermediate 1p*, ktp = 2.9 × 1012 s-1, observed using fs transient absorption spectroscopy, explains the sharp decrease in the fluorescence quantum yield of t-MeSt. We correct misconceptions that have appeared in the literature concerning the shape of the stilbene potential energy surface in S1. The nonplanarity due to methyl substitution leads to chirality issues that are relevant in biological molecules such as the protonated Schiff bases of retinal in the opsins.


Assuntos
Fotoquímica
9.
J Phys Chem A ; 125(20): 4323-4333, 2021 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-33998228

RESUMO

The structure of the novel Zintl phase, Cs5NbAs10, is reported for the first time. This compound crystallizes in the monoclinic P21/c space group (no. 14) with eight formula units per cell. The structure represents a unique atomic arrangement, constituting a new structure type with Wyckoff sequence e32. The most important structural element is the unprecedented [Nb(As5)2]5- cluster anion, formed by a Nb atom enclosed between two As5 rings. These nonaromatic cyclic species, formally [As5]5-, adopt an envelope conformation similar to that of cyclopentane. To date, it is only the second example of an [As5]5- ring with this conformation, reported in an inorganic solid-state compound. The bonding characteristics of the [Nb(As5)2]5- cluster and the [As5]5- rings are thoroughly investigated using first-principles methods and discussed. Electronic band structure calculations on Cs5NbAs10 suggest that this compound is a semiconductor with an estimated band gap of ca. 1.4 eV.

10.
Inorg Chem ; 60(9): 6327-6338, 2021 May 03.
Artigo em Inglês | MEDLINE | ID: mdl-33851821

RESUMO

Two series of high-spin nickel complexes, [TpPh,Me]Ni(EAr) (E = O, Se, Te; Ar = C6H5) and [TpPh,Me]Ni(SeC6H4-4-X) (X = H, Cl, Me, OMe), were prepared by metathetical reaction of the nickel(II) halide precursor with sodium salts of the corresponding chalcogen, NaEAr. X-ray crystallographic characterization and spectroscopic studies have established the geometric and electronic structures of these complexes. The observed spectroscopic and structural characteristics reveal distinct trends in accordance with the variation of the identity of the arylchalcogenolate and para substituent. Reaction of the [TpPh,Me]Ni(EAr) complexes with methyl iodide proceeded readily, producing the corresponding methylarylchalcogen and [TpPh,Me]NiI. A kinetic and computational analysis of the reaction of [TpPh,Me]Ni(SeC6H5) with MeI supports that the electrophilic alkylation reactions occur via an associative mechanism via a classical SN2 transition state.

11.
Angew Chem Int Ed Engl ; 60(27): 14975-14980, 2021 06 25.
Artigo em Inglês | MEDLINE | ID: mdl-33742526

RESUMO

trans-Cyclooctenes (TCOs) are essential partners in the fastest known bioorthogonal reactions, but current synthetic methods are limited by poor diastereoselectivity. Especially hard to access are hydrophilic TCOs with favorable physicochemical properties for live cell or in vivo experiments. Described is a new class of TCOs, "a-TCOs", prepared in high yield by stereocontrolled 1,2-additions of nucleophiles to trans-cyclooct-4-enone, which itself was prepared on a large scale in two steps from 1,5-cyclooctadiene. Computational transition-state models rationalize the diastereoselectivity of 1,2-additions to deliver a-TCO products, which were also shown to be more reactive than standard TCOs and less hydrophobic than even a trans-oxocene analogue. Illustrating the favorable physicochemical properties of a-TCOs, a fluorescent TAMRA derivative in live HeLa cells was shown to be cell-permeable through intracellular Diels-Alder chemistry and to wash out more rapidly than other TCOs.


Assuntos
Ciclo-Octanos/síntese química , Físico-Química , Reação de Cicloadição , Ciclo-Octanos/química , Células HeLa , Humanos , Estrutura Molecular , Estereoisomerismo
12.
J Phys Chem A ; 124(31): 6294-6302, 2020 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-32635729

RESUMO

Several independent determinations of the pKa values of trans-resveratrol in water have led to conflicting results. Singular value decomposition analysis of UV absorption spectra of trans-resveratrol (t-Resv) in N2-outgased aqueous solutions buffered to pH values in the 7.0-13.6 range yielded the UV spectra of the three anionic forms and the corresponding pKa values: pKa1 = 9.16, pKa2 = 9.77, and pKa3 = 10.55 in very good agreement with calculated theoretical values. The analysis of the absorption spectra guided the assignment of the fluorescence spectrum of each anionic form. With the resolved spectra on hand, we applied the Förster equation to estimate pKa* values of 2.5 and 0, respectively, for the p- and m-OH substituents of t-Resv in S1. Theory supports a proposed mechanism for the reaction of t-Resv anions with O2.

13.
J Phys Chem A ; 123(42): 9102-9112, 2019 Oct 24.
Artigo em Inglês | MEDLINE | ID: mdl-31557030

RESUMO

Diffusional quenching in isopentane (IP) glass at 77 K is demonstrated by the reduction of triphenylene phosphorescence lifetimes in the presence of 1,3-pentadiene and/or molecular oxygen. Fluorescence spectra and lifetimes of cis- and trans-1,2-di(1-methyl-2-naphthyl)ethene in IP glass at 77 K reveal that the cis → trans photoisomerization leads to the trapping of unstable conformers of the trans isomer. The claim that IP at 77 K is not sufficiently viscous to trap unstable photoproduct conformers is invalidated.

14.
Artigo em Inglês | MEDLINE | ID: mdl-30533699

RESUMO

We present here draft genome sequences of five Staphylococcus aureus strains obtained from children suffering from atopic dermatitis. The strains were determined to be of five different sequence types (sequence type 1 [ST1], ST7, ST8, ST15, and ST101) and carried a unique combination of superantigen-like protein (SSL) and serine protease genes.

15.
Chem Sci ; 9(7): 1953-1963, 2018 Feb 21.
Artigo em Inglês | MEDLINE | ID: mdl-29675242

RESUMO

A photochemical synthesis of AgNO3 complexes of trans-cycloheptene (TCH) and trans-1-sila-4-cycloheptene (Si-TCH) derivatives is described. A low temperature flow photoreactor was designed to enable the synthesis of carbocyclic TCH derivatives due to their thermal sensitivity in the absence of metal coordination. Unlike the free carbocycles, TCH·AgNO3 complexes can be handled at rt and stored for weeks in the freezer (-18 °C). Si-TCH·AgNO3 complexes are especially robust, and are bench stable for days at rt, and for months in the freezer. X-ray crystallography was used to characterize a Si-TCH·AgNO3 complex for the first time. With decomplexation of AgNO3in situ, metal-free TCO and Si-TCH derivatives can engage in a range of cycloaddition reactions as well as dihydroxylation reactions. Computation was used to predict that Si-TCH would engage in bioorthogonal reactions that are more rapid than the most reactive trans-cyclooctenes. Metal-free Si-TCH derivatives were shown to display good stability in solution, and to engage in the fastest bioorthogonal reaction reported to date (k2 1.14 × 107 M-1 s-1 in 9 : 1 H2O : MeOH). Utility in bioorthogonal protein labeling in live cells is described, including labeling of GFP with an unnatural tetrazine-containing amino acid. The reactivity and specificity of the Si-TCH reagents with tetrazines in live mammalian cells was also evaluated using the HaloTag platform. The cell labeling experiments show that Si-TCH derivatives are best suited as probe molecules in the cellular environment.

16.
Org Biomol Chem ; 15(35): 7476, 2017 09 13.
Artigo em Inglês | MEDLINE | ID: mdl-28848969

RESUMO

Correction for 'Computationally guided discovery of a reactive, hydrophilic trans-5-oxocene dienophile for bioorthogonal labeling' by William D. Lambert et al., Org. Biomol. Chem., 2017, 15, 6640-6644.

17.
Org Biomol Chem ; 15(31): 6640-6644, 2017 Aug 09.
Artigo em Inglês | MEDLINE | ID: mdl-28752889

RESUMO

The use of organic chemistry principles and prediction techniques has enabled the development of new bioorthogonal reactions. As this "toolbox" expands to include new reaction manifolds and orthogonal reaction pairings, the continued development of existing reactions remains an important objective. This is particularly important in cellular imaging, where non-specific background fluorescence has been linked to the hydrophobicity of the bioorthogonal moiety. Here we report that trans-5-oxocene (oxoTCO) displays enhanced reactivity and hydrophilicity compared to trans-cyclooctene (TCO) in the tetrazine ligation reaction. Aided by ab initio calculations we show that the insertion of a single oxygen atom into the trans-cyclooctene (TCO) ring system is sufficient to impart aqueous solubility and also results in significant rate acceleration by increasing angle strain. We demonstrate the rapid and quantitative cycloaddition of oxoTCO using a water-soluble tetrazine derivative and a protein substrate containing a site-specific genetically encoded tetrazine moiety both in vitro and in vivo. We anticipate that oxoTCO will find use in studies where hydrophilicity and fast bioconjugation kinetics are paramount.

18.
Infect Genet Evol ; 53: 189-194, 2017 09.
Artigo em Inglês | MEDLINE | ID: mdl-28600216

RESUMO

The aim of this study was to investigate the patterns of antimicrobial resistance and molecular features of methicillin-resistant Staphylococcus aureus (MRSA) isolates in Russia. Isolates recovered from hospital patients (n=480), healthy medical personnel (n=25), and healthy carriers (n=13) were included in the study. Hospital-acquired MRSA (HA-MRSA) demonstrated high resistance to ciprofloxacin, gentamicin, and chloramphenicol (76%-92%), moderate - to tetracycline, erythromycin, clindamycin, and rifampicin (38%-54%), and low - to fusidic acid, co-trimoxazole, mupirocin, and daptomycin (2%-7%). Elevated MIC (2.0µg/ml) of vancomycin was detected in 26% of isolates. All isolates were susceptible to linezolid and tigecycline. Multilocus sequence typing (MLST) revealed that CC8 isolates (ST8+ST239) constituted 83.1% of HA-MRSA and that this genetic lineage dominated in all regions from Krasnoyarsk to Saint Petersburg. A local ST239 variant harboring the tst gene (ST239Kras) was detected in Krasnoyarsk. The other HA-MRSA isolates belonged to clonal complex 5 (CC5) (21 isolates, 12.2%) and CC22 (2, 1.2%). The majority of CC5 isolates were affiliated with sequence type 228 (ST228) and were characterized with decreased susceptibility to ceftaroline (MIC=2µg/ml). We also detected, for the first time in Russia, livestock-associated MRSA (LA-MRSA) from clusters CC398 and CC97 in humans. Among the 2053 healthy persons screened for nasal carriage of S. aureus, the bacteria were isolated from 426 (21%); among them, 13 carried isolates identified as community-associated MRSA (CA-MRSA). Eleven of 13 CA-MRSA isolates belonged to ST22 (spa types t223, t3243, and t3689; SCCmec types IVa and IVc, agr type I, tst-positive) and were similar to the EMRSA-15/Middle Eastern variant (Gaza strain).


Assuntos
Antibacterianos/farmacologia , Farmacorresistência Bacteriana Múltipla/genética , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Staphylococcus aureus Resistente à Meticilina/genética , Infecções Estafilocócicas/tratamento farmacológico , Infecções Estafilocócicas/epidemiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Aminoglicosídeos/farmacologia , Cloranfenicol/farmacologia , Infecção Hospitalar , Feminino , Fluoroquinolonas/farmacologia , Humanos , Masculino , Staphylococcus aureus Resistente à Meticilina/classificação , Staphylococcus aureus Resistente à Meticilina/isolamento & purificação , Testes de Sensibilidade Microbiana , Pessoa de Meia-Idade , Epidemiologia Molecular , Tipagem de Sequências Multilocus , Federação Russa/epidemiologia , Infecções Estafilocócicas/microbiologia , Tetraciclinas/farmacologia , beta-Lactamas/farmacologia
19.
Chemistry ; 23(49): 11843-11855, 2017 Sep 04.
Artigo em Inglês | MEDLINE | ID: mdl-28544228

RESUMO

Metal carbenes appended with two electron-donating groups, known as "donor/donor" carbenes, undergo diastereo- and enantioselective rhodium-catalyzed C-H insertion reactions with ether substrates to form benzodihydrofurans. Unlike the reactions of metal carbenes with electron-withdrawing groups attached, the attenuated electrophilicity enables these reactions to be conducted in Lewis basic solvents (e.g., acetonitrile) and in the presence of water. The diazo precursors for these species are prepared in situ from hydrazone using a mild and chemoselective oxidant (MnO2 ). Although this sequence often can be performed in one-pot, control experiments have elucidated why a "two-pot" process is often more efficient. A thorough screening of achiral catalysts demonstrated that sterically encumbered catalysts are optimal for diastereoselective reactions. Although efficient insertion into allylic and propargylic C-H bonds is observed, competing dipolar cycloaddition processes are noted for some substrates. The full substrate scope of this useful method of benzodihydrofuran synthesis, mechanisms of side reactions, and computational support for the origins of stereoselectivity are described.

20.
J Phys Chem A ; 121(12): 2331-2342, 2017 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-28234492

RESUMO

We present a comparative study of the photoisomerizations of lumisterol (Lumi), previtamin (Pre), and provitamin D3 (Pro) to tachysterol (Tachy) at 77 K in EPA (5:5:2 ether, isopentane, and ethanol by volume) glass. Fluorescence, fluorescence excitation, and UV spectra, measured in the course of these reactions, were analyzed using singular value decomposition with self-modeling (SVD-SM). This represents an extension of previous work that led to the conclusion that in the EPA glass Pre exists as an s-cis,s-cis-conformer (cZc-Pre) which gives, exclusively, an unstable s-cis,s-cis-conformer of Tachy (cEc-Tachy) and Pro gives mainly the tEc-Tachy, that corresponds to a stable s-trans,s-cis-conformer. ( Redwood , C. ; et al. J. Phys. Chem. Lett. 2013 , 4 , 716 - 721 . ) The surprising result was that the major Pre photoproduct from Pro also has a tZc-Pre conformation instead of the expected cZc-Pre conformation. Accordingly, the Pre to Tachy cis-trans photoisomerization proceeds via a conformer specific one-bond-twist (OBT) process as proposed by Havinga ( Maessen , P. A. ; et al. Angew. Chem. Int. Ed. Engl. 1983 , 22 , 718 - 719 . Maessen , P. A. ; et al. Angew. Chem. Int. Ed. Engl. 1983 , 22 , 994 - 1004 . Maessen , P. A. Ph.D. Thesis, State University at Leiden, Leiden, The Netherlands, 1983. ). The role of the EPA glass in controlling conformer distributions and reaction outcomes is further explored by the extension of the studies to Lumi, whose structure differs substantially from that of its stereoisomer, Pro. Initially, the light-induced conrotatory ring openings of Pro and Lumi are expected to give cZc-Pre conformers that differ in the relative orientation of the double bond dihedral angles that define the chiral axis of the triene moiety: (-)cZ(-)c-Pre and (+)cZ(+)c-Pre, respectively. In the case of Pro, much of the cZc-Pre proceeds to tZc-Pre, the precursor of tEc-Tachy. In contrast, we show that under the same conditions most cZc-Pre formed from Lumi retains the cZc-conformation and isomerizes to cEc-Tachy. cZc-Pre from Lumi was not detected by fluorescence, but UV absorption measurements establish its formation as an essential intermediate to Tachy. Aided by theoretical calculations of conformer UV and CD spectra, we conclude that fluorescent thermodynamic Pre and nonfluorescent Pre from Lumi are both (+)cZ(+)c-Pre conformers. They differ in the orientation of the OH in the A ring, pseudoequatorial in the former and pseudoaxial in the latter. The most likely major photochemical sequences starting from Pre and Lumi are (+)cZ(+)c-Pre-eq-OH → (+)cE(+)c-Tachy-eq-OH and Lumi → (+)cZ(+)c-Pre-ax-OH → (+)cE(+)c-Tachy-eq-OH.


Assuntos
Colecalciferol/análogos & derivados , Ácido Eicosapentaenoico/química , Ergosterol/química , Vidro/química , Processos Fotoquímicos , Temperatura , Colecalciferol/síntese química , Colecalciferol/química , Isomerismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...