11 research outputs found
Kinetic Self-Sorting of Dynamic Covalent Catalysts with Systemic Feedback Regulation
Constructing
small molecule systems that mimic the functionality
exhibited in biological reaction networks is a key objective of systems
chemistry. Herein, we report the development of a dynamic catalytic
system where the catalyst activity is modulated through a dynamic
covalent bond. By connecting a thermodynamically controlled rearrangement
process to resolution under kinetic control, the catalyst system underwent
kinetic self-sorting, resulting in amplification of a more reactive
catalyst while establishing a catalytic feedback mechanism. The dynamic
catalyst system furthermore responded to catalytic events by self-perturbation
to regulate its own activity, which in the case of upregulation gave
rise to systemic autocatalytic behavior
Chirality Control in Enzyme-Catalyzed Dynamic Kinetic Resolution of 1,3-Oxathiolanes
The
origin of enantioenrichment in enzyme-catalyzed dynamic kinetic
resolution of 1,3-oxathiolane derivatives, key intermediates for asymmetric
lamivudine synthesis, was elucidated. The chirality control could
be determined by chiral HPLC and NOE NMR spectroscopy using a modified
1,3-oxathiolane compound obtained through enzyme-catalyzed selective
hydrolysis. Solvent-dependent stereoselectivity was observed under
biphasic conditions using different organic solvents with phosphate
buffer
<i>N</i>,<i>N</i>āDiethylurea-Catalyzed Amidation between Electron-Deficient Aryl Azides and Phenylacetaldehydes
Urea structures, of which <i>N</i>,<i>N</i>-diethylurea (DEU) proved to be the
most efficient, were discovered
to catalyze amidation reactions between electron-deficient aryl azides
and phenylacetaldehydes. Experimental data support 1,3-dipolar cycloaddition
between DEU-activated enols and electrophilic phenyl azides, especially
perfluoroaryl azides, followed by rearrangement of the triazoline
intermediate. The activation of the aldehyde under near-neutral conditions
was of special importance in inhibiting dehydration/aromatization
of the triazoline intermediate, thus promoting the rearrangement to
form aryl amides
Anilide Formation from Thioacids and Perfluoroaryl Azides
A metal-free
method for fast and clean anilide formation from perfluoroaryl
azide and thioacid is presented. The reaction proved highly efficient,
displaying fast kinetics, high yield, and good chemoselectivity. The
transformation was compatible with various solvents and tolerant to
a wide variety of functional groups, and it showed high performance
in polar protic/aprotic media, including aqueous buffer systems
Direct Measurement of Glyconanoparticles and Lectin Interactions by Isothermal Titration Calorimetry
Glyconanomaterials have shown high potential in applications
including
bioanalysis and nanomedicine. Here, a quantitative analytical technique,
based on isothermal titration calorimetry, was developed to characterize
the interactions between glyconanoparticles and lectins. By titrating
lectins into the glyconanoparticle solution, the apparent dissociation
constant, thermodynamic parameters, and the number of binding sites
were derived simultaneously. For the glyconanoparticlesālectin
binding pairs investigated, a 3ā5 order of magnitude affinity
enhancement over the free ligandālectin interactions was observed
which can be attributed to the multivalent ligand presentation on
the nanoparticles. The impact of ligand density was also studied,
and results showed that the affinity increased with the number of
glycans on the nanoparticle
Quantitative Fluorine NMR To Determine Carbohydrate Density on Glyconanomaterials Synthesized from Perfluorophenyl Azide-Functionalized Silica Nanoparticles by Click Reaction
A quantitative fluorine NMR (<sup>19</sup>F qNMR) method was developed
to determine the carbohydrate density on glyconanomaterials. Mannose
(Man)- and galactose (Gal)-conjugated silica nanoparticles (SNPs)
were synthesized from perfluorophenyl azide (PFPA)-functionalized
SNPs and propargylated Man or Gal by copper-catalyzed azideāalkyne
cycloaddition (click reaction). After treating PFPA-SNPs or Man-SNPs
with hydrofluoric acid followed by lyophilization, the remaining residues
were directly subjected to <sup>19</sup>F NMR analysis. The density
of PFPA on PFPA-SNP was determined to be 7.7 Ā± 0.2 Ć 10<sup>ā16</sup> nmol/nm<sup>2</sup> and Man on Man-SNP to be 6.4
Ā± 0.2 Ć 10<sup>ā16</sup> nmol/nm<sup>2</sup> giving
a yield of ā¼83% for the click coupling reaction. The apparent
dissociation constant (<i>K</i><sub>d</sub>) of Man-SNPs
with fluorescein isothiocyanate (FITC)-concanavalin A (Con A) was
determined using a fluorescence competition assay to be 0.289 Ā±
0.003 Ī¼M, which represents more than 3 orders of magnitude affinity
increase compared to free Man with Con A
1,3-Dipolar Cycloaddition Reactivities of Perfluorinated Aryl Azides with Enamines and Strained Dipolarophiles
The
reactivities of enamines and predistorted (strained) dipolarophiles
toward perfluoroaryl azides (PFAAs) were explored experimentally and
computationally. Kinetic analyses indicate that PFAAs undergo (3 +
2) cycloadditions with enamines up to 4 orders of magnitude faster
than phenyl azide reacts with these dipolarophiles. DFT calculations
were used to identify the origin of this rate acceleration. Orbital
interactions between the cycloaddends are larger due to the relatively
low-lying LUMO of PFAAs. The triazolines resulting from PFAAāenamine
cycloadditions rearrange to amidines at room temperature, while (3
+ 2) cycloadditions of enamines and phenyl azide yield stable, isolable
triazolines. The 1,3-dipolar cycloadditions of norbornene and DIBAC
also show increased reactivity toward PFAAs over phenyl azide but
are slower than enamineāazide cycloadditions
Stereoelectronic Control in Regioselective Carbohydrate Protection
Organotin-mediated regioselective protection has been
extensively
used in organic synthesis for many years. However, the mechanistic
origin of the resulting regioselectivity is still not clear. By the
comparison of the steric and stereoelectronic effects controlling
the geometry of five-membered rings formed from neighboring group
participation, from intramolecular acyl group migration, or from orthoester
transesterification on pyranoside rings, a theory on the pattern resulting
from the reaction with dibutyltin oxide is presented. It is thus suggested
that the regioselectivity of organotin-mediated protection is controlled
by analogous steric and stereoelectronic effects as in neighboring
group participation and acyl group migration, mainly dependent on
the stereoelectronic effects of the pyranoside itself, and not related
to complex stannylene structures. An organotin protection mechanism
is also suggested, emanating from steric and stereoelectronic effects,
nucleophilicity, and organotin acyl migration
Glycan-Functionalized Fluorescent Chitin Nanocrystals for Biorecognition Applications
A new
platform based on chitin nanocrystals has been developed
for biorecognition applications. TEMPO-oxidized chitin nanocrystals
(TCNs) were labeled with a fluorescent imidazoisoquinolinone dye,
and simultaneously conjugated with carbohydrate ligands, resulting
in dually functionalized TCNs. The biorecognition properties of the
nanocrystals were probed with lectins and bacteria, resulting in selective
interactions with their corresponding cognate carbohydrate-binding
proteins, as visualized by optical, fluorescence, STEM, and TEM imaging.
This represents a new approach to multifunctional nanomaterials based
on naturally occurring polymers, holding high potential for biomedical
applications
Trehalose-Conjugated, Photofunctionalized Mesoporous Silica Nanoparticles for Efficient Delivery of Isoniazid into Mycobacteria
Glyconanoparticle carriers have been
synthesized and efficiently
delivered into mycobacteria. Mesoporous silica nanoparticles were
functionalized with <i>Ī±,Ī±</i>-trehalose through
azide-mediated surface photoligation, and loaded with the antitubercular
drug isoniazid. The glyconanoparticles showed high isoniazid loading
capacity and higher antimicrobial activity than the free drug