The water-soluble, self-assembled, tetrahedral assembly K12Ga4L6 (L = 1,5-biscatecholamidenaphthalene) catalyzes the Nazarov cyclization of 1,3-pentadienols with extremely high levels of efficiency. ...The catalyzed reaction proceeds over a million times faster than the background reaction, an increase comparable to those observed in some enzymatic systems. This catalysis operates under aqueous conditions at mild temperatures and pH, and the reaction is halted by the addition of an appropriate inhibitor. This unprecedented rate enhancement is attributed to both the stabilization of protonated reaction intermediates and the effect of constrictive binding on the bound guest.
The use of micellar conditions to enable one-pot reactions involving both transition metal and enzymatic catalysts is reported. Representative enzymatic transformations under micellar conditions are ...unaffected by the presence of non-ionic surfactants, including designer surfactants such as TPGS-750-M. Furthermore, the presence of enzymes has a negligible effect on transition metal catalysis under micellar conditions in water. Finally, three one-pot chemoenzymatic reactions in water are reported in which the micelle-forming surfactant TPGS-750-M is a crucial factor for reaction efficiency.
Micelle-forming surfactants in water provide an optimal reaction medium for transition metal and enzyme catalysts, enabling efficient one-pot chemoenzymatic reactions in water.
The tetrahedral assembly Ga4L612− L = N,N-bis(2,3-dihydroxybenzoyl)-1,5-diaminonaphthalene) encapsulates a variety of cations, including propargyl enammonium cations capable of undergoing the aza ...Cope rearrangement. For propargyl enammonium substrates that are encapsulated in the Ga4L612− assembly, rate accelerations by factors of up to 184 compared with the background reaction rate were observed. After rearrangement, the product iminium ion is released into solution and hydrolyzed, allowing for catalytic turnover. The activation parameters for the catalyzed and uncatalyzed reaction were determined, revealing that a decrease in the entropy of activation is responsible for the observed rate enhancements. The catalyzed reaction exhibits saturation kinetics: the rate data obeyed the Michaelis−Menten model of enzyme kinetics, and competitive inhibition using a nonreactive guest was demonstrated.
The kinetically controlled, regioselective deprotonation of cyclopentenyl cations is mediated by encapsulation within a metal–ligand assembly. The regiochemistry of the deprotonation step determines ...which one of two possible products is formed. Moreover, subtle differences in the stereochemistry of the encapsulated cation switch the selectivity of this process (see scheme).
The self‐assembled supramolecular host Ga4L612− (1; L=N,N‐bis(2,3‐dihydroxybenzoyl)‐1,5‐diaminonaphthalene) catalyzes the Nazarov cyclization of 1,3‐pentadienols with extremely high levels of ...efficiency. The catalyzed reaction proceeds at a rate over a million times faster than that of the background reaction, an increase comparable to those observed in some enzymatic systems. A detailed study was conducted to elucidate the reaction mechanism of both the catalyzed and uncatalyzed Nazarov cyclization of pentadienols. Kinetic analysis and 18O‐exchange experiments implicate a mechanism, in which encapsulation, protonation, and water loss from substrate are reversible, followed by irreversible electrocyclization. Although electrocyclization is rate determining in the uncatalyzed reaction, the barrier for water loss and for electrocyclization are nearly equal in the assembly‐catalyzed reaction. Analysis of the energetics of the catalyzed and uncatalyzed reaction revealed that transition‐state stabilization contributes significantly to the dramatically enhanced rate of the catalyzed reaction.
A self‐assembled supramolecular host catalyzes the Nazarov cyclization of 1,3‐pentadienols under mild, aqueous conditions. The catalyzed reaction rate is enhanced by a factor of over 106 compared with the background reaction rate, one of the largest reported for supramolecular catalysis. Analysis of the reaction‐energy profile revealed that transition‐state stabilization contributes significantly to the dramatically enhanced reaction rate (see scheme).
Driven by the hydrophobic effect, a water-soluble, chiral, self-assembled supramolecular host is able to encapsulate hydrophobic organic guests in aqueous solution. Small aromatics can be ...encapsulated in the supramolecular assembly, and the simultaneous encapsulation of multiple species is observed in many cases. The molecular host assembly is able to recognize different substitutional isomers of disubstituted benzenes with
ortho substitution leading to the encapsulation of two guests, but
meta or
para substitution leading to the encapsulation of only one guest. The scope of hydrophobic guest encapsulation is further explored with chiral natural products. Upon encapsulation of chiral molecules into the racemic host, diastereomeric host–guest complexes are formed with observed diastereoselectivities of up to 78:22 in the case of fenchone.
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The designer surfactant TPGS-750-M is an important technology for green and sustainable chemical synthesis that facilitates a wide variety of organic transformations in water. Despite its growing ...importance in organic synthesis, many basic aspects of binding and reactivity within TPGS-750-M micelles remain poorly understood. In this work, the impact of TPGS-750-M on the rate of p-nitrophenyl ester hydrolysis kinetics was investigated to probe binding strength within TPGS-750-M micelles and the chemical environment of the micelle interior. We found that the hydrolysis rates of p-nitrophenyl acetate and p-nitrophenyl hexanoate were slowed by the presence of TPGS-750-M by up to 92%, consistent with a hydrophobic encapsulation environment within the micelle interior. The hydrolysis rates of p-nitrophenyl decanoate and p-nitrophenyl hydroxycinnamate were accelerated up to 74-fold by the presence of TPGS-750-M, but only at low surfactant concentrations. We propose that these rate enhancements are due to mixed micelle formation between ester and TPGS-750-M, which positions the reactive ester group within the hydrophilic region of the micelle. This study suggests that there are two distinct chemical environments present in the interior of micelles derived from TPGS-750-M, and that it is possible for very hydrophobic substrates to interact with the polar, hydrophilic region of the micelle. This work also demonstrates that increased hydrophobicity leads to stronger substrate binding within TPGS-750-M micelles.
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Die kinetisch kontrollierte, regioselektive Deprotonierung von Cyclopentenylkationen wird durch Verkapselung mit einem Metall‐Ligand‐Aggregat vermittelt. Die Regiochemie des Deprotonierungsschritts ...bestimmt, welches der beiden möglichen Produkte gebildet wird. Feine Unterschied in der Stereochemie des Kations kehren zudem die Selektivität des Prozesses um (siehe Schema).
To evaluate short- and long-term measures of health care utilization-days in the emergency department (ED), inpatient (IP) care, and rehabilitation in a post-acute care (PAC) facility-to understand ...how home time (i.e., days alive and not in an acute or PAC setting) corresponds to quality of life (QoL).
Survey data on community-residing veterans combined with multipayer administrative data on health care utilization.
VA or Medicare health care utilization, quantified as days of care received in the ED, IP, and PAC in the 6 and 18 months preceding survey completion, were used to predict seven QoL-related measures collected during the survey. Elastic net machine learning was used to construct models, with resulting regression coefficients used to develop a weighted utilization variable. This was then compared with an unweighted count of days with any utilization.
In the short term (6 months), PAC utilization emerged as the most salient predictor of decreased QoL, whereas no setting predominated in the long term (18 months). Results varied by outcome and time frame, with some protective effects observed. In the 6-month time frame, each weighted day of utilization was associated with a greater likelihood of activity of daily living deficits (0.5%, 95% CI: 0.1%-0.9%), as was the case with each unweighted day of utilization (0.6%, 95% CI: 0.3%-1.0%). The same was true in the 18-month time frame (for both weighted and unweighted, 0.1%, 95% CI: 0.0%-0.3%). Days of utilization were also significantly associated with greater rates of instrumental ADL deficits and fair/poor health, albeit not consistently across all models. Neither measure outperformed the other in direct comparisons.
These results can provide guidance on how to measure home time using multipayer administrative data. While no setting predominated in the long term, all settings were significant predictors of QoL measures.
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