Enantioseparation and racemization of 3-fluorooxindoles.

Fluorinated oxindoles are frequently used building blocks in asymmetric synthesis and represent an important scaffold found in a variety of biologically relevant compounds. While it is understood that incorporation of fluorine atoms into organic molecules can improve their pharmacological properties, the impact on the configurational stability of chiral organofluorines is still underexplored. In this study, semipreparative HPLC enantioseparations of five oxindoles were carried out, and the resulting enantiomerically enriched solutions were used to investigate base promoted racemization kinetics at room temperature. It was found that incorporation of fluorine at the chiral center increases the configurational stability, while substitutions on the aromatic ring and at the lactam moiety also have significant effects on the rate of racemization, which generally follows reversible first-order reaction kinetics.

Enantioseparation and racemization of α-aryl-α-fluoroacetonitriles.

The 2-Aryl-2-fluoroacetonitriles have garnered increasing interest as versatile building blocks in asymmetric synthesis. However, the configurational stability of these organofluorines is poorly understood and analytical methods that can be used to differentiate between their enantiomers remain underdeveloped. In this study, baseline high performance liquid chromatography (HPLC) enantioseparation of ten 2-aryl-2-fluoroacetonitriles was achieved by screening frequently used chiral stationary phases. While Chiralcel OD, Chiralpak AD, and Chiralpak AS proved to be most broadly useful, preparative separation of the enantiomers of 2-(2-naphthyl)-2-fluoroacetonitrile was possible on Chiralcel OJ. This enabled racemization studies at various temperatures and in the presence of organic bases which showed that this compound is configurationally stable under neutral conditions upon heating to 130°C for 6 h but undergoes complete racemization within 10 h in the presence of stoichiometric amounts of a guanidine base at room temperature. The racemization is likely to proceed via formation of an achiral keteniminate intermediate and obeys reversible first-order reaction kinetics with a half-life time of 87.7 min in ethanolic hexanes at 23.2°C. Racemization is significantly slower and occurs with a half-life time of 23.1 h at 22.4°C when the guanidine is replaced with a weaker amidine base.

Neural Processing of Cognitive Control in an Emotionally Neutral Context in Anxiety Patients.

Impaired cognitive control plays a crucial role in anxiety disorders and is associated with deficient neural mechanisms in the fronto-parietal network. Usually, these deficits were found in tasks with an emotional context. The present study aimed at investigating electrophysiological and vascular signatures from event-related brain potentials (ERPs) and functional near-infrared spectroscopy (fNIRS) in anxiety patients versus healthy controls during an inhibition task integrated in an emotionally neutral context. Neural markers were acquired during the completion of a classical Eriksen flanker task. The focus of data analysis has been the ERPs N200 and P300 and fNIRS activations in addition to task performance. No behavioral or neural group differences were identified. ERP findings showed a larger N2pc and a delayed and reduced P300 for incongruent stimuli. The N2pc modulation suggests the reorienting of attention to salient stimuli, while the P300 indicates longer lasting stimulus evaluation processes due to increased task difficulty. FNIRS did not result in any significant activation potentially suggesting a contribution from deeper brain areas not measurable with fNIRS. The missing group difference in our non-emotional task indicates that no generalized cognitive control deficit but rather a more emotionally driven deficit is present in anxiety patients.

The challenge of learning a new language in adulthood: Evidence from a multi-methodological neuroscientific approach.

Being proficient in several foreign languages is an essential part of every-day life. In contrast to childhood, learning a new language can be highly challenging for adults. The present study aims at investigating neural mechanisms supporting very initial foreign language learning in adulthood. For this reason, subjects underwent an implicit semantic associative training in which they had to learn new pseudoword-picture pairings. Learning success was measured via a recognition experiment presenting learned versus new pseudoword-picture pairings. Neural correlates were assessed by an innovative multi-methodological approach simultaneously applying electroencephalography (EEG) and functional near-infrared spectroscopy (fNIRS). Results indicate memory-related processes based on familiarity and mechanisms of cognitive control to be present during initial vocabulary learning. Findings underline the fascinating plasticity of the adult brain during foreign language learning, even after a short semantic training of only 18 minutes as well as the importance of comparing evidence from different neuroscientific methods and behavioral data.

So young, yet so mature? Electrophysiological and vascular correlates of phonotactic processing in 18-month-olds.

The present study investigated neural correlates of implicit phonotactic processing in 18-month-old children that just reached an important step in language development: the vocabulary spurt. Pseudowords, either phonotactically legal or illegal with respect to their native language, were acoustically presented to monolingually German raised infants. Neural activity was simultaneously assessed by means of electroencephalography (EEG) and functional near-infrared spectroscopy (fNIRS). The former method excellently tracks fast processing mechanisms, whereas the latter reveals brain areas recruited. Results of the present study indicate that 18-month-olds recognize the linguistic properties of their native language based on phonotactics. This manifested in an increased N400 for legal compared to illegal pseudowords in the EEG conforming to adult-like mechanisms. Unfortunately, fNIRS findings did not support this discrimination ability. Possible methodological and brain maturational reasons might explain this null finding. This study provides evidence for the advantage of a multi-methodological approach in order to get a clear picture on neural language development.

Uncovering electrophysiological and vascular signatures of implicit emotional prosody.

The capability of differentiating between various emotional states in speech displays a crucial prerequisite for successful social interactions. The aim of the present study was to investigate neural processes underlying this differentiating ability by applying a simultaneous neuroscientific approach in order to gain both electrophysiological (via electroencephalography, EEG) and vascular (via functional near-infrared-spectroscopy, fNIRS) responses. Pseudowords conforming to angry, happy, and neutral prosody were presented acoustically to participants using a passive listening paradigm in order to capture implicit mechanisms of emotional prosody processing. Event-related brain potentials (ERPs) revealed a larger P200 and an increased late positive potential (LPP) for happy prosody as well as larger negativities for angry and neutral prosody compared to happy prosody around 500 ms. FNIRS results showed increased activations for angry prosody at right fronto-temporal areas. Correlation between negativity in the EEG and activation in fNIRS for angry prosody suggests analogous underlying processes resembling a negativity bias. Overall, results indicate that mechanisms of emotional and phonological encoding (P200), emotional evaluation (increased negativities) as well as emotional arousal and relevance (LPP) are present during implicit processing of emotional prosody.

How Therapeutic Tapping Can Alter Neural Correlates of Emotional Prosody Processing in Anxiety.

Anxiety disorders are the most common psychological disorders worldwide resulting in a great demand of adequate and cost-effective treatment. New short-term interventions can be used as an effective adjunct or alternative to pharmaco- and psychotherapy. One of these approaches is therapeutic tapping. It combines somatic stimulation of acupressure points with elements from Cognitive Behavioral Therapy (CBT). Tapping reduces anxiety symptoms after only one session. Anxiety is associated with a deficient emotion regulation for threatening stimuli. These deficits are compensated e.g., by CBT. Whether Tapping can also elicit similar modulations and which dynamic neural correlates are affected was subject to this study. Anxiety patients were assessed listening to pseudowords with a different emotional prosody (happy, angry, fearful, and neutral) prior and after one Tapping session. The emotion-related component Late Positive Potential (LPP) was investigated via electroencephalography. Progressive Muscle Relaxation (PMR) served as control intervention. Results showed LPP reductions for negative stimuli after the interventions. Interestingly, PMR influenced fearful and Tapping altered angry prosody. While PMR generally reduced arousal for fearful prosody, Tapping specifically affected fear-eliciting, angry stimuli, and might thus be able to reduce anxiety symptoms. Findings highlight the efficacy of Tapping and its impact on neural correlates of emotion regulation.