3 research outputs found
Copper(I) Nitrosyls from Reaction of Copper(II) Thiolates with <i>S</i>âNitrosothiols: Mechanism of NO Release from RSNOs at Cu
<i>S</i>-nitrosothiols (RSNOs) serve as ready sources
of biological nitric oxide activity, especially in conjunction with
copper centers. We report a novel pathway for the generation of NO
within the coordination sphere of copper model complexes from reaction
of copperÂ(II) thiolates with <i>S</i>-nitrosothiols. Reaction
of trisÂ(pyrazolyl)Âborate copperÂ(II) thiolates <sup>iPr2</sup>TpCuâSR
(R = C<sub>6</sub>F<sub>5</sub> or CPh<sub>3</sub>) with <sup>t</sup>BuSNO leads to formation of <sup>iPr2</sup>TpCuÂ(NO) and the unsymmetrical
disulfide RSâS<sup>t</sup>Bu. Quantum mechanical investigations
with B3LYP-D3/6-311GÂ(d) suggest formation of a Îş<sup>1</sup>-NâRSNO adduct <sup>iPr2</sup>TpCuÂ(SR)Â(Râ˛SNO) that
precedes release of RSSRⲠto deliver <sup>iPr2</sup>TpCuÂ(NO).
This process is reversible; reaction of <sup>iPr2</sup>TpCuÂ(NO) (but
not <sup>iPr2</sup>TpCuÂ(NCMe)) with C<sub>6</sub>F<sub>5</sub>SâSC<sub>6</sub>F<sub>5</sub> forms <sup>iPr2</sup>TpCuâSC<sub>6</sub>F<sub>5</sub>. Coupled with the facile, reversible reaction between <sup>iPr2</sup>TpCuÂ(NO) and C<sub>6</sub>F<sub>5</sub>SNO to give <sup>iPr2</sup>TpCuâSC<sub>6</sub>F<sub>5</sub> and 2 equiv NO,
we outline a new, detailed catalytic cycle for NO generation from
RSNOs at Cu
Spiroligozymes for Transesterifications: Design and Relationship of Structure to Activity
Transesterification catalysts based on stereochemically
defined,
modular, functionalized ladder-molecules (named spiroligozymes) were
designed, using the âinside-outâ design strategy, and
mutated synthetically to improve catalysis. A series of stereochemically
and regiochemically diverse bifunctional spiroligozymes were first
synthesized to identify the best arrangement of a pyridine as a general
base catalyst and an alcohol nucleophile to accelerate attack on vinyl
trifluoroacetate as an electrophile. The best bifunctional spiroligozyme
reacted with vinyl trifluoroacetate to form an acyl-spiroligozyme
conjugate 2.7 Ă 10<sup>3</sup>-fold faster than the background
reaction with a benzyl alcohol. Two trifunctional spiroligozymes were
then synthesized that combined a urea with the pyridine and alcohol
to act as an oxyanion hole and activate the bound acyl-spiroligozyme
intermediate to enable acyl-transfer to methanol. The best trifunctional
spiroligozyme carries out multiple turnovers and acts as a transesterification
catalyst with <i>k</i><sub>1</sub>/<i>k</i><sub>uncat</sub> of 2.2 Ă 10<sup>3</sup> and <i>k</i><sub>2</sub>/<i>k</i><sub>uncat</sub> of 1.3 Ă 10<sup>2</sup>. Quantum mechanical calculations identified the four transition
states of the catalytic cycle and provided a detailed view of every
stage of the transesterification reaction
Computational Design of Enone-Binding Proteins with Catalytic Activity for the MoritaâBaylisâHillman Reaction
The MoritaâBaylisâHillman reaction forms
a carbonâcarbon
bond between the Îą-carbon of a conjugated carbonyl compound
and a carbon electrophile. The reaction mechanism involves Michael
addition of a nucleophile catalyst at the carbonyl β-carbon,
followed by bond formation with the electrophile and catalyst disassociation
to release the product. We used Rosetta to design 48 proteins containing
active sites predicted to carry out this mechanism, of which two show
catalytic activity by mass spectrometry (MS). Substrate labeling measured
by MS and site-directed mutagenesis experiments show that the designed
active-site residues are responsible for activity, although rate acceleration
over background is modest. To characterize the designed proteins,
we developed a fluorescence-based screen for intermediate formation
in cell lysates, carried out microsecond molecular dynamics simulations,
and solved X-ray crystal structures. These data indicate a partially
formed active site and suggest several clear avenues for designing
more active catalysts