Search NASA⌕ Search

SEARCH · Search NASA

Results for “HYDROLYSIS”

Search indexed NASA NTRS and DOE OSTI research on propulsion, heat transfer, battery materials and energy systems. Follow report and document links to the original sources.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 127 records · Page 7
All sourcesNASA NTRSDOE OSTI
DOE OSTI2022

An active site loop toggles between conformations to control antibiotic hydrolysis and inhibition potency for CTX-M β-lactamase drug-resistance enzymes

Abstract β-lactamases inactivate β-lactam antibiotics leading to drug resistance. Consequently, inhibitors of β-lactamases can combat this resistance, and the β-lactamase inhibitory protein (BLIP) is a naturally occurring inhibitor. The widespread CTX-M-14 and CTX-M-15 β-lactamases have an 83% sequence identity. In this study, we show that BLIP weakly inhibits CTX-M-14 but potently inhibits CTX-M-15. The structure of the BLIP/CTX-M-15 complex reveals that binding is associated with a conformational change of an active site loop of β-lactamase. Surprisingly, the loop structure in the complex is similar to that in a drug-resistant variant (N106S) of CTX-M-14. We hypothesized that the pre-established favorable loop conformation of the N106S mutant would facilitate binding. The N106S substitution results in a ~100- and 10-fold increase in BLIP inhibition potency for CTX-M-14 and CTX-M-15, respectively. Thus, this indicates that an active site loop in β-lactamase toggles between conformations that control antibiotic hydrolysis and inhibitor susceptibility. These findings highlight the role of accessible active site conformations in controlling enzyme activity and inhibitor susceptibility as well as the influence of mutations in selectively stabilizing discrete conformations.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2022

A theoretical investigation of the hydrolysis of uranium hexafluoride: the initiation mechanism and vibrational spectroscopy

Depleted uranium hexafluoride (UF 6 ), a stockpiled byproduct of the nuclear fuel cycle, reacts readily with atmospheric humidity, but the mechanism is poorly understood. Here we compare several potential initiation steps at a consistent level of theory, generating underlying structures and vibrational modes using hybrid density functional theory (DFT) and computing relative energies of stationary points with double-hybrid (DH) DFT. A benchmark comparison is performed to assess the quality of DH-DFT data using reference energy differences obtained using a complete-basis-limit coupled-cluster (CC) composite method. The associated large-basis CC computations were enabled by a new general-purpose pseudopotential capability implemented as part of this work. Dispersion-corrected parameter-free DH-DFT methods, namely PBE0-DH-D3(BJ) and PBE-QIDH-D3(BJ), provided mean unsigned errors within chemical accuracy (1 kcal mol -1 ) for a set of barrier heights corresponding to the most energetically favorable initiation steps. The hydrolysis mechanism is found to proceed via intermolecular hydrogen transfer within van der Waals complexes involving UF 6 , UF 5 OH, and UOF 4 , in agreement with previous studies, followed by the formation of a previously unappreciated dihydroxide intermediate, UF 4 (OH) 2 . The dihydroxide is predicted to form under both kinetic and thermodynamic control, and, unlike the alternate pathway leading to the UO 2 F 2 monomer, its reaction energy is exothermic, in agreement with observation. Finally, harmonic and anharmonic vibrational simulations are performed to reinterpret literature infrared spectroscopy in light of this newly identified species.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2023

Design of supported organocatalysts from a biomass-derived difuran compound and catalytic assessment for lactose hydrolysis

The engineered structures and active sites of enzyme catalysts give rise to high catalytic activity and selectivity toward desired reactions. We have employed a biomass-derived difuran compound to append N-substituted maleimides with amino acid (glutamic acid) substitution by Diels–Alder reaction to mimic the chemical functional groups that comprise the active site channels in enzyme catalysts. The difunctionality of the biomass-derived difuran allows production of Diels–Alder adducts by appending two amino acid moieties to form a difunctional organocatalyst. The catalytic activity of the organocatalyst can be improved by immobilizing the organocatalyst on solid supporting materials. Accordingly, the structures of these immobilized organocatalysts can be engineered to mimic enzymatic active sites and to control the interaction between reactants, products, and transition states of catalytic reactions. Lactose hydrolysis was carried out to provide an example of industrial application of this approach to design and fabricate new supported organocatalysts as artificial enzymes.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2022

Step-stool conformation of a cyclic Schiff base derived from ethylenediamine and heptane-2,4,6-trione: evidence for partial hydrolysis in metal coordination

A Schiff base derived from ethylenediamine and heptane-2,4,6-trione, namely, 5,9,14,18-tetramethyl-1,4,10,13-tetraazacyclooctadeca-5,8,14,17-tetraene-7,16- dione (C 18 H 28 N 4 O 2 ), abbreviated H 4 daaden, was prepared and characterized for the first time by single-crystal X-ray diffraction. The atoms of the Schiff base occupy two different planes and thus the molecule is essentially nonplanar. An axis running through the C–C atoms of the ethylenediamine groups separate the two planes and these two planes are connected by bridging ethylene groups showing an angle of 117.34 (8)°. As a result, the side view of the molecule shows a ‘step-stool’ conformation. The nonplanar nature of the Schiff base plays an important role in metal coordination, which leads to partial hydrolysis of the ring structure

crystal structure↗
DOE OSTI2022

Circularity in mixed-plastic chemical recycling enabled by variable rates of polydiketoenamine hydrolysis

Footwear, carpet, automotive interiors, and multilayer packaging are examples of products manufactured from several types of polymers whose inextricability poses substantial challenges for recycling at the end of life. Here, we show that chemical circularity in mixed-polymer recycling becomes possible by controlling the rates of depolymerization of polydiketoenamines (PDK) over several orders of magnitude through molecular engineering. Stepwise deconstruction of mixed-PDK composites, laminates, and assemblies is chemospecific, allowing a prescribed subset of monomers, fillers, and additives to be recovered under pristine condition at each stage of the recycling process. We provide a theoretical framework to understand PDK depolymerization via acid-catalyzed hydrolysis and experimentally validate trends predicted for the rate-limiting step. The control achieved by PDK resins in managing chemical and material entropy points to wide-ranging opportunities for pairing circular design with sustainable manufacturing.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗