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Amyloid fibril formation is associated with various amyloidoses, including neurodegenerative diseases such as Alzheimer's and Parkinson's diseases. Despite the numerous studies on the inhibition of amyloid formation, the prevention and treatment of a majority of amyloid-related disorders are still challenging. In this study, we investigated the effects of various plant extracts on amyloid formation of α-synuclein. We found that the extracts from Eucalyptus gunnii are able to inhibit amyloid formation, and to disaggregate preformed fibrils, in vitro. The extract itself did not lead cell damage. In the extract, miquelianin, which is a glycosylated form of quercetin and has been detected in the plasma and the brain, was identified and assessed to have a moderate inhibitory activity, compared to the effects of ellagic acid and quercetin, which are strong inhibitors for amyloid formation. The properties of miquelianin provide insights into the mechanisms controlling the assembly of α-synuclein in the brain.
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BACKGROUND: The risk of postoperative recurrence is higher in lung cancer patients who smoke than non-smokers. However, objective evaluation of the postoperative recurrence risk is difficult using conventional pathological prognostic factors because of their lack of reproducibility. Consequently, novel objective biomarkers that reflect postoperative risk in lung cancer patients who smoke must be identified. Because cigarette smoking and oncogenesis alter lipid metabolism in lung tissue, we hypothesized that the lipid profiles in lung cancer tissues are influenced by cigarette smoking and can reflect the postoperative recurrence risk in smoking lung cancer patients. This study aimed to identify lipid biomarkers that reflect the smoking status and the postoperative recurrence risk. METHODS: Primary tumor tissues of lung adenocarcinoma (ADC) (n = 26) and squamous cell carcinoma (SQCC) (n = 18) obtained from surgery were assigned to subgroups according to the patient's smoking status. The ADC cohort was divided into never smoker and smoker groups, while the SQCC cohort was divided into moderate smoker and heavy smoker groups. Extracted lipids from the tumor tissues were subjected to liquid chromatography-tandem mass spectrometry analysis. Lipids that were influenced by smoking status and reflected postoperative recurrence and pathological prognostic factors were screened. RESULTS: Two and 12 lipid peaks in the ADC and SQCC cohorts showed a significant positive correlation with the Brinkman index, respectively. Among them, in the ADC cohort, a higher lipid level consisted of three phosphatidylcholine (PC) isomers, PC (14:0_18:2), PC (16:1_16:1), and PC (16:0_16:2), was associated with a shorter recurrence free period (RFP) and a greater likelihoods of progressed T-factor (≥ pT2) and pleural invasion. In the SQCC cohort, a lower m/z 736.5276 level was associated with shorter RFP and greater likelihood of recurrence. CONCLUSIONS: From our data, we propose three PC isomers, PC (14:0_18:2), PC (16:1_16:1), and PC (16:0_16:2), and a lipid peak of m/z 736.5276 as novel candidate biomarkers for postoperative recurrence risk in lung ADC and SQCC patients who are smokers.
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Adenocarcinoma de Pulmão , Carcinoma de Células Escamosas , Neoplasias Pulmonares , Humanos , Estudos de Casos e Controles , Reprodutibilidade dos Testes , Neoplasias Pulmonares/etiologia , Neoplasias Pulmonares/cirurgia , Carcinoma de Células Escamosas/patologia , Biomarcadores Tumorais/análise , Fumar/efeitos adversos , LipídeosRESUMO
Not all encapsulation techniques are universally apt for every type of phase change material (PCM), highlighting the imperative for methodological precision. This study addresses the challenges of microencapsulated PCM (MEPCM) arising from the immiscible pairing of α-Al2O3 nanoparticles with Sn microparticles. The high-speed impact blending (HIB) dry synthesis technique is employed, facilitating large-volume production of Sn@α-Al2O3 MEPCMs. The resulting MEPCMs not only seamlessly endure 100 cycles of melting-solidification but also, with the strategic incorporation of a glass frit, exhibit remarkable thermal durability, withstanding up to 1000 melting-solidification cycles. Even under ultrafast thermal fluctuations, the α-Al2O3 shell remained resilient through 100 cycles. A marked reduction in supercooling is observed, which is attributed to the formation of SnO and SnO2 nanoparticles within the α-Al2O3 crystal lattice. The atomically resolved interface dynamics between SnO2 and α-Al2O3 play a pivotal role, lowering the energy barrier for Sn nuclei formation during solidification. This affects the accelerated Sn nucleation rate, effectively suppressing supercooling. Such insights offer a deeper understanding of the interplay between nanoscale crystal lattice imperfections and their implications for energy storage applications.
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Risperidone (Ris) is a second-generation antipsychotic that belongs to the chemical class of benzisoxazole derivatives. 9-Hydroxy (9OH-) Ris is well known among the six reported metabolites of Ris and had been examined using not only blood but also other matrices, but the other five metabolites reported such as benzisoxazole ring-cleaved Ris (c-Ris) and c-9OH-Ris had been detected only in blood, urine and feces. In the present work, large peaks of c-Ris and c-9OH-Ris were detected in the liver, kidney, cerebrum, blood, pericardial fluid, bile and urine obtained from two cadavers. There is a potential that c-Ris and c-9OH-Ris will be good markers to prove Ris consumption in forensic toxicology cases. For example, the peak ratios of c-Ris against the parent Ris in the kidney and blood were as high as 3.9 and 3.6 in cadaver 1; and 7.0 and 7.9 in cadaver 2, respectively. In addition to the previously reported six metabolites, five new metabolites such as dehydrogenated-Ris, 7-keto-Ris and three benzisoxazole ring-cleaved metabolites were disclosed in the present work, and the pathways for the totally eleven metabolites detected in human solid tissues and body fluids have also been proposed, because such pathways were neither reported nor discussed previously.
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Antipsicóticos , Bile , Cadáver , Rim , Líquido Pericárdico , Risperidona , Espectrometria de Massas em Tandem , Humanos , Risperidona/análise , Risperidona/metabolismo , Bile/química , Rim/química , Rim/metabolismo , Masculino , Líquido Pericárdico/química , Líquido Pericárdico/metabolismo , Fígado/química , Fígado/metabolismo , Toxicologia Forense/métodos , Feminino , Distribuição Tecidual , Química Encefálica , Líquidos Corporais/química , Cromatografia LíquidaRESUMO
In whitish parts of teleost skin, the coloration is attributed to a light scattering phenomenon within light-reflecting chromatophores, namely leucophores and iridophores, which contain high refractive index materials in their cytoplasmic organelles, leucosomes and light-reflecting platelets, respectively. Previous chemical examinations revealed that guanine is a major constituent of the materials in the platelets of the iridophores, while, in leucophores, the detailed chemical nature of the materials contained in the leucosomes has not been reported. Here, using liquid chromatography-tandem mass spectroscopy, we investigated the chemical features of materials eluted from scales, larvae, and single chromatophores of the medaka. Results of the liquid chromatography-tandem mass spectroscopy suggested that uric acid is a major constituent of the high refractive index materials in medaka leucophores and is a unique marker to investigate the presence of leucophores in the fish. The whitish appearance of the medaka leucophores may be attributed to the light-scattering phenomenon in leucosomes, which contain highly concentrated uric acid.
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Cromatóforos , Oryzias , Animais , Ácido Úrico , Pigmentação da Pele , PeleRESUMO
Risperidone (RIS) is an atypical antipsychotic agent and its 9-hydroxylated metabolite named paliperidone (PAL) also has pharmacological properties similar to that of RIS. Quantifications of RIS and PAL in authentic human biological fluids and solid tissues by liquid chromatography (LC)-tandem mass spectrometry (MS/MS) have not been reported yet although those in plasma (and blood) were reported abundantly. In the present work, a quantification method for RIS and PAL based on the standard addition method was devised and validated for the human fluid and solid tissue specimens. RIS and PAL in biological fluids were quantified only after their dilution and deproteinization. The concentrations of RIS and PAL in the heart whole blood, pericardial fluid, stomach contents, bile, urine, liver, kidney and cerebrum were determined for a deceased who had been treated with RIS therapeutically, and also a deceased who had ingested RIS with other drugs intentionally. To our knowledge, this is the first report on the quantification of RIS and PAL by LC-MS/MS in the authentic human tissues and biological fluids.
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PURPOSE: Quantification of olanzapine (OLZ) and its metabolites such as N-desmethylolanzapine (DM-O), 2-hydroxymethylolanzapine (2H-O) and olanzapine N-oxide (NO-O) in five kinds of human body fluids including whole blood by liquid chromatography (LC)-tandem mass spectrometry (MS/MS) has been presented; the quantification methods were carefully devised and validated using the matrix-matched calibration and standard addition methods. METHODS: OLZ and its three metabolites were extracted from 40 µL each of body fluids by two-step liquid-liquid separations. The samples and reagents were pre-cooled in a container filled with ice for the extraction because of the thermal instability of OLZ and its three metabolites especially in whole blood. RESULTS: The limits of quantification (LOQs) of OLZ and 2H-O were 0.05 ng/mL and those of DM-O and NO-O were 0.15 ng/mL in whole blood and urine, respectively. The concentrations of OLZ and its metabolites in heart whole blood, pericardial fluid, stomach contents, bile and urine were determined for two cadavers and those in whole blood and urine for the other two cadavers. The reduction from NO-O to OLZ was observed at 25 â in whole blood in vitro. CONCLUSIONS: To our knowledge, this is the first report on the quantification of metabolites of olanzapine in the authentic human body fluids by LC-MS/MS as well as on the confirmation of in vitro reduction from NO-O to OLZ in whole blood that seems to have induced the quick decrease of NO-O.
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Líquido Pericárdico , Espectrometria de Massas em Tandem , Humanos , Olanzapina , Cromatografia Líquida/métodos , Espectrometria de Massas em Tandem/métodos , CadáverRESUMO
In patients with unresectable non-small cell lung cancer, histological diagnosis is frequently based on small biopsy specimens unsuitable for histological diagnosis when they are severely crushed and do not retain their morphology. Therefore, establishing a novel diagnostic method independent of tissue morphology or conventional immunohistochemistry (IHC) markers is required. We analyzed the lipid profiles of resected primary lung adenocarcinoma (ADC) and squamous cell carcinoma (SQCC) specimens using liquid chromatography-tandem mass spectrometry. The specimens of 26 ADC and 18 SQCC cases were evenly assigned to the discovery and validation cohorts. Non-target screening on the discovery cohort identified 96 and 13 lipid peaks abundant in ADC and SQCC, respectively. Among these 109 lipid peaks, six and six lipid peaks in ADC and SQCC showed reproducibility in target screening on the validation cohort. Finally, we selected three and four positive lipid markers for ADC and SQCC, demonstrating high discrimination abilities. In cases difficult to diagnose by IHC staining, [cardiolipin(18:2_18:2_18:2_18:2)-H]- and [triglyceride(18:1_17:1_18:1) + NH4]+ showed the excellent diagnostic ability for ADC (sensitivity: 1.00, specificity: 0.89, accuracy: 0.93) and SQCC (sensitivity: 0.89, specificity: 0.83, accuracy: 0.87), respectively. These novel candidate lipid markers may contribute to a more accurate diagnosis and subsequent treatment strategy for unresectable NSCLC.
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Adenocarcinoma de Pulmão , Adenocarcinoma , Carcinoma Pulmonar de Células não Pequenas , Carcinoma de Células Escamosas , Neoplasias Pulmonares , Humanos , Carcinoma Pulmonar de Células não Pequenas/patologia , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patologia , Reprodutibilidade dos Testes , Carcinoma de Células Escamosas/diagnóstico , Carcinoma de Células Escamosas/patologia , Adenocarcinoma/diagnóstico , Adenocarcinoma/patologia , Lipídeos , Biomarcadores Tumorais/análiseRESUMO
A 54-year-old art teacher, experienced a right putaminal hemorrhage, and thereafter suffered severe left hemiplegia and unilateral spatial neglect, and was transferred to the rehabilitation department of the University Hospital 1 month after the onset. Although the unilateral spatial neglect was improving, the patient was unable to paint the left quarter of a watercolor, but there was no error in line drawing. The occurrence of errors only in a watercolor suggests that the neural process for painting a watercolor is different from that of line drawing.
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Lateralidade Funcional , Hemiplegia/complicações , Transtornos da Percepção/etiologia , Desempenho Psicomotor/fisiologia , Percepção Espacial/fisiologia , Humanos , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Campos Visuais/fisiologiaRESUMO
PURPOSE: The aim of this study is to investigate the stabilities of the 24 synthetic cannabinoid metabolites (SCMs) in blood and urine at various temperatures from - 30 to 37 â stored for 1-168 days. In addition, experiments of stabilities at lower temperatures and for much longer duration have been performed as described below. METHODS: The quantification was performed by liquid chromatography-tandem mass spectrometry (LC-MS/MS). The blank blood and urine spiked with SCMs and non-spiked real case (authentic) specimens were incubated at 37 â up to 56 days and at 22, 4 or - 30 â up to 168 days. The non-spiked authentic blood and urine specimens were also stored at - 30 or - 80 â for 1, 3 or 5 years to investigate stabilities during very long time frames. RESULTS: All the 24 SCMs were much more stable in urine than in blood at 37, 22 or 4 â. All 24 SCMs spiked into blood or urine were stable at - 30 â for up to 168 days. The 6 SCMs in the authentic specimens exhibited long stabilities at - 30 or - 80 â for 3-5 years. Some tendencies were observed according to the relation between the structures of SCMs and their stabilities. CONCLUSIONS: The long-term stabilities of 24 SCMs in spiked samples and those of 6 SCMs in the authentic specimens were examined using LC-MS/MS. SCMs were largely very stable and usable several years after storage at - 30 or - 80 â.
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Líquidos Corporais , Canabinoides , Cromatografia Líquida , Espectrometria de Massas em Tandem , TemperaturaRESUMO
The blue light using flavin (BLUF) domain photosensors, such as the transcriptional antirepressor AppA, utilize a noncovalently bound flavin as the chromophore for photoreception. Since the isoalloxazine ring of the chromophore is unable to undergo large-scale structural change upon light absorption, there is intense interest in understanding how the BLUF protein matrix senses and responds to flavin photoexcitation. Light absorption is proposed to result in alterations in the hydrogen-bonding network that surrounds the flavin chromophore on an ultrafast time scale, and the structural changes caused by photoexcitation are being probed by vibrational spectroscopy. Here we report ultrafast time-resolved infrared spectra of the AppA BLUF domain (AppA(BLUF)) reconstituted with isotopically labeled riboflavin (Rf) and flavin adenine dinucleotide (FAD), which permit the first unambiguous assignment of ground and excited state modes arising directly from the flavin carbonyl groups. Studies of model compounds and DFT calculations of the ground state vibrational spectra reveal the sensitivity of these modes to their environment, indicating that they can be used as probes of structural dynamics.
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Proteínas de Bactérias/química , Proteínas de Bactérias/metabolismo , Flavoproteínas/química , Flavoproteínas/metabolismo , Luz , Rhodobacter sphaeroides , Espectrofotometria Infravermelho/métodos , Flavina-Adenina Dinucleotídeo/metabolismo , Marcação por Isótopo , Cinética , Estrutura Terciária de Proteína , VibraçãoRESUMO
Ultrafast proton transfer dynamics on a short H-bond in a protein were studied through the time-resolved fluorescence of the S65T/H148D green fluorescent protein (GFP) mutant. In response to the change in chromophore pK(a) upon excitation, the donor-proton-acceptor structure evolves on a sub-100 fs time scale, followed by picosecond time scale vibrational cooling and host structure reorganization.
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Proteínas de Fluorescência Verde/análise , Prótons , Proteínas de Fluorescência Verde/genética , Ligação de Hidrogênio , Modelos Moleculares , Proteínas Mutantes/análise , Proteínas Mutantes/genética , Espectrometria de FluorescênciaRESUMO
The effects of confinement on the ultrafast torsional reaction of auramine O in aqueous solution are investigated through ultrafast fluorescence up-conversion with 50 fs time resolution. The aqueous solution is confined in nanoscale water droplets by an ionic surfactant. The torsional motion is orders of magnitude slower in the confined droplets than in bulk aqueous solution. The dynamics become faster with increasing radius of the nanodroplet but never reach the bulk value, even when the radius is as large as 10 nm. Time-dependent fluorescence spectra were constructed and subsequently analyzed using a one-dimensional generalized Smoluchowski equation. An accurate description of the data was achieved using a time-dependent diffusion coefficient. This is suggested to arise because the medium friction reflects dynamics on a broad range of time scales spanning the reaction dynamics. The friction recovered suggests strongly hindered motion in the confined droplet and can be qualitatively related to solvation dynamics measured in AOT, consistent with auramine O torsional dynamics being accompanied by intramolecular charge redistribution.
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Benzofenoneídio/química , Ácido Dioctil Sulfossuccínico/química , Micelas , Nanoestruturas/química , Tensoativos/química , Termodinâmica , Água/química , Estrutura Molecular , Espectrometria de Fluorescência , Fatores de TempoRESUMO
The excited-state dynamics of a reactive dye molecule, auramine O, have been studied in nanoscale water droplets stabilized by a nonionic surfactant. Spectral dynamics were measured as a function of the radius of the water nanodroplet with 50 fs time resolution using time-resolved fluorescence up-conversion method. Qualitatively, the effect of confinement is to dramatically slow the rate of the reaction compared to that of bulk water. Data were quantitatively analyzed using the one-dimensional generalized Smoluchowski equation assuming a time-dependent diffusion coefficient. The results were contrasted with our earlier analysis of auramine O in aqueous nanodroplets stabilized by the ionic surfactant AOT. The excited-state reaction is slower in the nonionic surfactant, showing that interfacial charge is not required to suppress reactions in nanoscale water droplets. The location of the dye in the heterogeneous micelle is investigated by comparing the absorption spectra of AO in the micelle with those of a water- polyethyleneglycol mixture (to mimic the surfactant head group). The results suggest that the charged dye is located in the water phase.
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Benzofenoneídio/química , Ácido Dioctil Sulfossuccínico/química , Nanoestruturas/química , Tensoativos/química , Água/química , Fricção , Micelas , Estrutura Molecular , Polietilenoglicóis/química , Espectrometria de Fluorescência , Eletricidade Estática , Fatores de TempoRESUMO
To examine a dynamic interaction between nucleotide and cyclic oligosaccharide, ultrasonic absorption measurements were carried out in aqueous solution containing beta-cyclodextrin (beta-CD) and adenosine 5'-monophosphate (AMP) in the frequency range of 0.8-95 MHz. A relaxational absorption was observed in the solution, although it was not found in the individual solution of beta-CD or AMP. From the concentration dependences of AMP on the relaxation time and the maximum absorption per wavelength, the cause of the relaxation was attributed to a perturbation of a chemical equilibrium associated with a complex formation between beta-CD (host) and AMP (guest). The rate constants for the formation and breakup processes of the complex were determined. Also, a standard volume change of the reaction was obtained. From comparisons of the obtained rate and thermodynamic parameters with those for beta-CD and various guests, it has been concluded that the adenine moiety is included in the beta-CD cavity and that the hydrogen bonds may play a role in the complex formation.
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Nucleotídeos/química , Ultrassom , beta-Ciclodextrinas/química , Adenina/química , Monofosfato de Adenosina/química , Guanina/química , Cinética , Soluções , Análise Espectral , TermodinâmicaRESUMO
Ultrasonic absorption coefficients in the frequency range of 0.8-95 MHz were measured in aqueous solutions containing both beta-cyclodextrin (beta-CD) (host) and butanoic acid (in its dissociated form and undissociated one) (guest). A single relaxational phenomenon was observed only when the solutes were coexisting, although no relaxation was found in the beta-CD solution or in the acid solutions. The absorption was also measured in a solution of pentanoic acid (dissociated form) with beta-CD, and single relaxation was detected. The ultrasonic relaxation observed in these solutions was due to a perturbation of a chemical equilibrium related to a reaction of an inclusion complex formed by the host and guest. The equilibrium constant was obtained from the dependence of the maximum absorption per wavelength on the guest concentration. The rate constant for the inclusion process of the guest into a cavity of beta-CD and that for the leaving process from the cavity were determined from the obtained relaxation frequency and the equilibrium constant. The standard volume change of the reaction was also computed from the maximum absorption per wavelength. These results were compared with those in solutions containing both beta-CD and different guest molecules. It was found that the hydrophobicity of guest molecules played an important role in the formation of the inclusion complex and also that the charge on the carboxylic group had a considerable effect on the kinetic characteristics of the complexation reaction.
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Ácidos Carboxílicos/química , Ultrassom , beta-Ciclodextrinas/química , CinéticaRESUMO
A single ultrasonic relaxational phenomenon was observed in aqueous solutions containing both beta-cyclodextrin (beta-CD) as host and nonionized or ionized acetylsalicylic acid (aspirin) as guest. The observed relaxation was responsible for a dynamic complexation reaction between beta-CD and aspirin molecules, concomitant with a volume change during the reaction. The kinetic and equilibrium constants for the complexation in the acid (nonionized) form of the aspirin system were derived from the guest concentration dependence of the relaxation frequency. The equilibrium constant for the carboxylate (ionized) form of aspirin was determined from the concentration dependence of a maximum absorption per wavelength, and the rate constants were calculated by using the determined equilibrium constant and the observed relaxation frequencies, which remained nearly almost constant over the concentration range studied. The results showed that the effect of charge on the aspirin molecule was reflected only in the dissociation process from the beta-CD cavity, while no remarkable change was seen in the association process whose rate was diffusion controlled. The results could be explained on the basis of the difference of the hydrophobic moieties in the two guests that were included in the host cavity. The results of the standard volume change for the complexation reaction were closely related to the number of expelled water molecules originally located in the beta-CD cavity and the volume of the aspirin molecule incorporated into the beta-CD cavity.
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Aspirina/química , Soluções , Ultrassom , beta-Ciclodextrinas/química , Concentração de Íons de Hidrogênio , Soluções/química , Água/químicaRESUMO
Ultrafast time-resolved infrared (TRIR) spectra of flavin adenine dinucleotide (FAD) and the anion of lumiflavin (Lf-) are described. Ground-state recovery and excited-state decay of FAD reveal a common dominant ultrafast relaxation and a minor slower component. The Lf- transient lacks a fast component. No intermediate species are observed, suggesting that the quenching mechanism is internal conversion promoted by interaction of the adenine and isoalloxazine rings in FAD. Modes are assigned, and the potential for extension of the TRIR method to photoactive proteins is discussed.
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Físico-Química/métodos , Flavinas/química , Fotoquímica/métodos , Espectrofotometria Infravermelho/métodos , Espectrofotometria/métodos , Ânions , Cinética , Modelos Químicos , Modelos Estatísticos , Distribuição NormalRESUMO
The photophysics of trans-2-[4-(dimethylamino)styryl]benzothiazole (DMASBT) was investigated by electronic structure calculations and steady-state and time-resolved emission spectroscopy in a wide range of solvents, including temperature and pressure dependence. DMASBT undergoes a facile photoinduced trans-cis isomerization similar to the reaction of trans-stilbene. The cis isomer has a lifetime of â¼1 ps and does not contribute appreciably to the steady-state emission spectrum. The absorption spectrum of the cis form overlaps that of the trans form such that considerable care is needed in determining correct emission quantum yields. The approximate equality of absorption and emission transition moments of DMASBT in all solvents indicates that absorption and emission involve a single excited state with high radiative rate. The low quantum yields of DMASBT in low-viscosity solvents reflect emission lifetimes in the 20-50 ps range. The nonradiative rates of DMASBT, which are assumed to measure the rate of isomerization in S1, depend upon both solvent viscosity and polarity. A modified Kramers analysis, which allows for a polarity-dependent barrier height, provides a satisfactory description of these rates but only if it is assumed that friction in alcohol solvents is more weakly dependent upon viscosity than in other types of solvents.
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The rates of excited-state intramolecular electron transfer in 9-(4-biphenyl)-10-methylacridinium (BPAc(+)), crystal violet lactone (CVL), and bianthryl have been measured in a variety of ionic liquids using time-correlated single-photon counting. All three of these reactions had previously been studied in conventional dipolar solvents and their reaction rates shown to be controlled by solvation dynamics. The main focus of this work is to ask whether the same relationships between reaction and solvation times already established in dipolar solvents also apply in ionic liquids. In BPAc(+), where reaction conforms to a simple two-state kinetic scheme and reaction rates are easily measured, the result is a clear "yes". In the case of bianthryl, whose spectra reflect the more complex kinetics of a barrierless process, the answer is also yes. In contrast to other recent studies of bianthryl, the present results demonstrate that the same equality between (integral) reaction times and solvation times observed in conventional solvents also applies in ionic liquids. Finally, the case of CVL is less clear due to the greater uncertainty associated with the data afforded by this weak fluorophore, combined with a lack of data in conventional solvents having large solvation times. But the CVL reaction can also be reasonably interpreted as exhibiting a common behavior in dipolar and ionic solvents.