Bending a Cumulene with Electrons: Stepwise Chemical Reduction and Structural Study of a Tetraaryl[4]Cumulene.

Chemical reduction of a [4]cumulene with cesium metal was explored, and the structural changes stemming from electron acquisition are detailed using X-ray crystallography. It is found that the [4]cumulene undergoes dramatic geometric changes upon stepwise reduction, including bending of the cumulenic core and twisting of the endgroups from orthogonal to planar. The structural deformation is consistent with early theoretical reports that suggest that the twisting should occur upon reduction of both even and odd [n]cumulenes. The current results, on the other hand, are inconsistent with a previous experimental study of a [3]cumulene in which the predicted twisting is not observed upon reduction. DFT calculations reveal that the barrier to deformation is an order of magnitude lower in a [3]cumulene than a [4]cumulene, allowing the barrier to be overcome in the solid-state.

Lewis or Brønsted? A Rectification of the Acidic and Aromatic Nature of Boranol-Containing Naphthoid Heterocycles.

Boron-containing heterocycles are important in a variety of applications from drug discovery to materials science; therefore a clear understanding of their structure and reactivity is desirable to optimize these functions. Although the boranol (B-OH) unit of boronic acids behaves as a Lewis acid to form a tetravalent trihydroxyborate conjugate base, it has been proposed that pseudoaromatic hemiboronic acids may possess sufficient aromatic character to act as Brønsted acids and form a boron oxy conjugate base, thereby avoiding the disruption of ring aromaticity that would occur with a tetravalent boronate anion. Until now no firm evidence existed to ascertain the structure of the conjugate base and the aromatic character of the boron-containing ring of hemiboronic "naphthoid" isosteres. Here, these questions are addressed with a combination of experimental, spectroscopic, X-ray crystallographic, and computational studies of a series of model benzoxazaborine and benzodiazaborine naphthoids. Although these hemiboronic heterocycles are unambiguously shown to behave as Lewis acids in aqueous solutions, boraza derivatives possess partial aromaticity provided their nitrogen lone electron pair is sufficiently available to participate in extended delocalization. As demonstrated by dynamic exchange and crossover experiments, these heterocycles are stable in neutral aqueous medium, and their measured pKa values are consistent with the ability of the endocyclic heteroatom substituent to stabilize a partial negative charge in the conjugate base. Altogether, this study corrects previous inaccuracies and provides conclusions regarding the properties of these compounds that are important toward the methodical application of hemiboronic and other boron heterocycles in catalysis, bioconjugation, and medicinal chemistry.

Risk-taking bias in human decision-making is encoded via a right-left brain push-pull system.

A person's decisions vary even when options stay the same, like when a gambler changes bets despite constant odds of winning. Internal bias (e.g., emotion) contributes to this variability and is shaped by past outcomes, yet its neurobiology during decision-making is not well understood. To map neural circuits encoding bias, we administered a gambling task to 10 participants implanted with intracerebral depth electrodes in cortical and subcortical structures. We predicted the variability in betting behavior within and across patients by individual bias, which is estimated through a dynamical model of choice. Our analysis further revealed that high-frequency activity increased in the right hemisphere when participants were biased toward risky bets, while it increased in the left hemisphere when participants were biased away from risky bets. Our findings provide electrophysiological evidence that risk-taking bias is a lateralized push-pull neural system governing counterintuitive and highly variable decision-making in humans.

Computational Mechanistic Analysis of Intramolecular Cycloadditions of the 1,3-Dithiolium Cation with Adjacent Alkene and Allene Functional Groups.

In this work, the molecular mechanisms for the intramolecular cycloaddition reactions of the 1,3-dithiolium cation with adjacent alkenyl and allenyl groups were investigated by density functional theory calculations. Transition states for the mechanistic steps were searched, and their connections to corresponding reactive intermediates were validated by the intrinsic reaction coordinate method. Our studies demonstrate that both the alkenyl and allenyl groups can readily react with a neighboring 1,3-dithiolium cation first through a one-step asynchronous [3 + 2] cycloaddition path, with moderate activation energy barriers (ca. 20-30 kcal/mol) to overcome. Subsequent to the intramolecular dithiolium-alkene/allene cycloadditions, the resulting intermediates continue to undergo a series of reactions, including rearrangement, ring opening, and deprotonation to eventually yield the thermodynamically favored products, which carry a fused tricyclic molecular skeleton, 3,8-dihydro-2H-indeno[2,1-b]thiophene. Detailed geometric and energetic properties for all of the stationary points (transition states and intermediates) on the reaction potential surfaces have been calculated and examined. Key transition states and reactive intermediates were subjected to quantum theory of atoms in molecules and natural bonding orbital calculations to elucidate their bonding features and the stabilizing effects arising from orbital interactions. Finally, a comparative study using the continuum solvation model based on the charge density was conducted to evaluate the solvent effects on the intramolecular dithiolium-alkene/allene cycloadditions, which are the rate-limiting steps of the overall reactions. The results show that different organic solvents (polar and nonpolar) do not lead to much variations in the heights of activation energy barriers and hence indicate that solvent effects are actually insignificant on the reactions.

The influences and neural correlates of past and present during gambling in humans.

During financial decision-making tasks, humans often make "rational" decisions, where they maximize expected reward. However, this rationality may compete with a bias that reflects past outcomes. That is, if one just lost money or won money, this may impact future decisions. It is unclear how past outcomes influence future decisions in humans, and how neural circuits encode present and past information. In this study, six human subjects performed a financial decision-making task while we recorded local field potentials from multiple brain structures. We constructed a model for each subject characterizing bets on each trial as a function of present and past information. The models suggest that some patients are more influenced by previous trial outcomes (i.e., previous return and risk) than others who stick to more fixed decision strategies. In addition, past return and present risk modulated with the activity in the cuneus; while present return and past risk modulated with the activity in the superior temporal gyrus and the angular gyrus, respectively. Our findings suggest that these structures play a role in decision-making beyond their classical functions by incorporating predictions and risks in humans' decision strategy, and provide new insight into how humans link their internal biases to decisions.

Lucky Rhythms in Orbitofrontal Cortex Bias Gambling Decisions in Humans.

It is well established that emotions influence our decisions, yet the neural basis of this biasing effect is not well understood. Here we directly recorded local field potentials from the OrbitoFrontal Cortex (OFC) in five human subjects performing a financial decision-making task. We observed a striking increase in gamma-band (36-50 Hz) oscillatory activity that reflected subjects' decisions to make riskier choices. Additionally, these gamma rhythms were linked back to mismatched expectations or "luck" occurring in past trials. Specifically, when a subject expected to win but lost, the trial was defined as "unlucky" and when the subject expected to lose but won, the trial was defined as "lucky". Finally, a fading memory model of luck correlated to an objective measure of emotion, heart rate variability. Our findings suggest OFC may play a pivotal role in processing a subject's internal (emotional) state during financial decision-making, a particularly interesting result in light of the more recent "cognitive map" theory of OFC function.

Neural systems involved in processing novel linguistic constructions and their visual referents.

In language, abstract phrasal patterns provide an important source of meaning, but little is known about whether or how such constructions are used to predict upcoming visual scenes. Findings from two fMRI studies indicate that initial exposure to a novel construction allows its semantics to be used for such predictions. Specifically, greater activity in the ventral striatum, a region sensitive to prediction errors, was linked to worse overall comprehension of a novel construction. Moreover, activity in occipital cortex was attenuated when a visual event could be inferred from a learned construction, which may reflect predictive coding of the event. These effects disappeared when predictions were unlikely: that is, when phrases provided no additional information about visual events. These findings support the idea that learners create and evaluate predictions about new instances during comprehension of novel linguistic constructions.

Performing behavioral tasks in subjects with intracranial electrodes.

Patients having stereo-electroencephalography (SEEG) electrode, subdural grid or depth electrode implants have a multitude of electrodes implanted in different areas of their brain for the localization of their seizure focus and eloquent areas. After implantation, the patient must remain in the hospital until the pathological area of brain is found and possibly resected. During this time, these patients offer a unique opportunity to the research community because any number of behavioral paradigms can be performed to uncover the neural correlates that guide behavior. Here we present a method for recording brain activity from intracranial implants as subjects perform a behavioral task designed to assess decision-making and reward encoding. All electrophysiological data from the intracranial electrodes are recorded during the behavioral task, allowing for the examination of the many brain areas involved in a single function at time scales relevant to behavior. Moreover, and unlike animal studies, human patients can learn a wide variety of behavioral tasks quickly, allowing for the ability to perform more than one task in the same subject or for performing controls. Despite the many advantages of this technique for understanding human brain function, there are also methodological limitations that we discuss, including environmental factors, analgesic effects, time constraints and recordings from diseased tissue. This method may be easily implemented by any institution that performs intracranial assessments; providing the opportunity to directly examine human brain function during behavior.

Successful creation of tissue-engineered autologous auricular cartilage in an immunocompetent large animal model.

Tissue-engineered cartilage has historically been an attractive alternative treatment option for auricular reconstruction. However, the ability to reliably generate autologous auricular neocartilage in an immunocompetent preclinical model should first be established. The objectives of this study were to demonstrate engineered autologous auricular cartilage in the immunologically aggressive subcutaneous environment of an immunocompetent animal model, and to determine the impact of in vitro culture duration of chondrocyte-seeded constructs on the quality of neocartilage maturation in vivo. Auricular cartilage was harvested from eight adult sheep; chondrocytes were isolated, expanded in vitro, and seeded onto fibrous collagen scaffolds. Constructs were cultured in vitro for 2, 6, and 12 weeks, and then implanted autologously in sheep and in control nude mice for 6 and 12 weeks. Explanted tissue was stained with hematoxylin and eosin, safranin O, toluidine blue, collagen type II, and elastin. DNA and glycosaminoglycans (GAGs) were quantified. The quality of cartilage engineered in sheep decreased with prolonged in vitro culture time. Superior cartilage formation was demonstrated after 2 weeks of in vitro culture; the neocartilage quality improved with increased implantation time. In nude mice, neocartilage resembled native sheep auricular cartilage regardless of the in vitro culture length, with the exception of elastin expression. The DNA quantification was similar in all engineered and native cartilage (p>0.1). All cartilage engineered in sheep had significantly less GAG than native cartilage (p<0.02); significantly more GAG was observed with increased implantation time (p<0.02). In mice, the GAG content was similar to that of native cartilage and became significantly higher with increased in vitro or in vivo durations (p<0.02). Autologous auricular cartilage was successfully engineered in the subcutaneous environment of an ovine model using expanded chondrocytes seeded on a fibrous collagen scaffold after a 2-week in vitro culture period.