Engineering Papers⌕ Search

SEARCH · Engineering Papers

Results for “ligand design”

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 145 records · Page 8
All sourcesNASA NTRSDOE OSTI
DOE OSTI2026

Improving productivity and stability for CO 2 hydrogenation by using pincer-ligated Mn complexes with hemilabile ligands

Pincer ligands are widely used to support transition metal catalysts, but first-row systems often deactivate too quickly for widespread use. Here, pincer ligands bearing an additional hemilabile donor were designed to stabilize Mn catalysts for CO 2 hydrogenation to formate. Ligands of the type (RCH 2 CH 2 )N(CH 2 CH 2 P i Pr 2 ) 2 ( iPr PN R P; R = OMe, CH 2 OMe, NMe 2 , P i Pr 2 ) were synthesized and coordinated to Mn to form complexes of the type ( iPr PN R P)Mn(CO) 2 H. Their performance was compared to {MeN(CH 2 CH 2 P i Pr 2 ) 2 }Mn(CO) 2 H, which lacks a pendant donor. The pendant donor identity and arm length strongly influenced catalytic activity, but all pendant arm containing systems extended catalyst lifetime. Notably, ( iPr PN CH2OMe P)Mn(CO) 2 H achieved turnover frequencies of 158,000 h -1 and turnover numbers of 838,000, exceeding most state-of-the-art catalysts. Mechanistic studies revealed that hemilabile coordination enhances stability by avoiding deactivation, although excessive binding can lead to inactive states. Here, this work demonstrates hemilabile donors dramatically improve pincer-based Mn catalysts and provides design principles for broader applications.

CO2 hydrogenation↗
DOE OSTI2023

Chromophore carbonyl twisting in fluorescent biosensors encodes direct readout of protein conformations with multicolor switching

Fluorescent labeling of proteins is a powerful tool for probing structure-function relationships with many biosensing applications. Structure-based rules for systematically designing fluorescent biosensors require understanding ligand-mediated fluorescent response mechanisms which can be challenging to establish. We installed thiol-reactive derivatives of the naphthalene-based fluorophore Prodan into bacterial periplasmic glucose-binding proteins. Glucose binding elicited paired color exchanges in the excited and ground states of these conjugates. X-ray structures and mutagenesis studies established that glucose-mediated color switching arises from steric interactions that couple protein conformational changes to twisting of the Prodan carbonyl relative to its naphthalene plane. Mutations of residues contacting the carbonyl can optimize color switching by altering fluorophore conformational equilibria in the apo and glucose-bound proteins. A commonly accepted view is that Prodan derivatives report on protein conformations via solvatochromic effects due to changes in the dielectric of their local environment. Here we show that instead Prodan carbonyl twisting controls color switching. These insights enable structure-based biosensor design by coupling ligand-mediated protein conformational changes to internal chromophore twists through specific steric interactions between fluorophore and protein.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2025

Bis( tert -butoxydiphenylsilyl)amide Divalent Lanthanide Complexes

The development of new ligand systems to stabilize “nontraditional/ non-classical” divalent lanthanides is key to tuning the chemical and physical properties of their mixed principal quantum number 4f n 5d 1 ground states. The design and study of novel ligand systems which stabilize occupation of differing orbitals within the 5d manifold for these ions constitutes an area ripe for exploration. Our efforts toward the development of redox-innocent bulky silylamide ligands to stabilize pseudo-octahedral coordination geometries for divalent lanthanides have resulted in the synthesis of the bis( tert -butoxydiphenylsilyl) amide ligand, whose coordination complexes with Sm 2+ , Eu 2+ , and Yb 2+ are reported herein. These systems have been fully characterized by single-crystal X-ray diffraction, elemental analysis, cyclic voltammetry, direct-current magnetometry, and infrared, nuclear magnetic resonance, and electronic absorption spectroscopies. Attempts to extend this system to the more reducing Tm 2+ ion resulted in an inseparable mixture of products from which crystals of the analogous Tm 2+ species and a reduced dinitrogen, bimetallic Tm 3+ -Tm 3+ complex bridged by a η 2 -N 2 3− radical could be identified. Though progress toward six-coordinate complexes of reducing “traditional/ classical” divalent ions is noted for these systems, further work is needed to improve the synthetic utility of this ligand framework for the study of “non-traditional/non-classical” divalent lanthanides with a mixed-principal quantum number 4f n 5d 1 ground state.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2025

Structure-function studies of Vibrio cholerae quorum-sensing receptor CqsR signal recognition

Ethanolamine signaling through the transmembrane quorum-sensing receptor CqsR influencesVibrio choleraeniche recognition and host colonization. In this study, we present a comprehensive structure-function analysis of CqsR. Specifically, we have determined X-ray crystal structures of the CqsR periplasmic domain bound to the signaling agonist ethanolamine and its analogs, serinol and L-alaninol, as well as the ligand-free (apo) form of CqsR. The periplasmic ligand-binding domain of CqsR is a Cache domain, the most prevalent extracellular sensory module in prokaryotes. Our findings provide a rare structural comparison of ligand-bound and unbound states of a Cache domain receptor. Coupled with thermodynamic binding assays and genetic analyses, these structures elucidate the molecular basis of CqsR ligand specificity. This study not only advances the understanding of Cache domain function but also informs the identification of ligands for orphan Cache receptors and the rational design of signaling agonists and antagonists. Lastly, we discuss ligand-induced conformational changes in the CqsR Cache domains and explore the potential for the existence of additional regulatory ligands.

Microbiology↗
DOE OSTI2026

Selective Bidentate Coordination Reconstructs Residual PbI 2 to Homogenize Interfacial Energetics in Perovskite Solar Cells

Spatially heterogeneous interfacial energetics, often originating from residual lead iodide (PbI 2 ), represent a fundamental bottleneck to both the efficiency and operational stability of perovskite photovoltaics. Conventional PbI 2 passivation strategies based on monodentate ligands or highly polar solvents either interact weakly with PbI 2 or undesirably perturb the underlying three-dimensional perovskite lattice. Here, we report a diammonium bidentate strategy that selectively reconstructs residual PbI 2 into corner-sharing PbI 6 octahedra while preserving the bulk perovskite. Enabled by dual-site coordination, a newly designed thiophene-based bidentate ligand (MeXT) stabilizes PbI 6 units during passivation and establishes spatially homogeneous interfacial energetics. Perovskite solar cells incorporating MeXT achieve 26.19% power conversion efficiency and retain over 80% of their initial efficiency after 1000 h of continuous 1-sun illumination at 75 °C. This dual-anchor coordination passivation strategy establishes a general design principle for selectively treating residual PbI 2 and creating electronically coherent and operationally stable interfaces in perovskite photovoltaics.

ligands↗
DOE OSTI2020

A Ligand-Directed Nitrophenol Carbonate for Transient in situ Bioconjugation and Drug Delivery

Here we report the first use of ligand-directed proximity accelerated bioconjugation chemistry in the tandem delivery and release of a therapeutic payload. To do this, we designed a nitrophenol carbonate for ligand-directed in situ bioconjugation of a prodrug payload to a protein. The transient nature of our conjugation chemistry renders the protein a depot for timedependent release of active drug following hydrolysis and selfimmolation. In our model system, using an immunostimulant prodrug, biotin ligand, and avidin protein, we observe release of bioavailable immunostimulant both spectroscopically and with an immune cell line over 48 h. Avidin co-crystalized with the nitrophenolate directing group verified the binding pose of the ligand and offered insight into the mechanism of in situ bioconjugation. Overall, this scaffold warrants further investigation for the time-dependent delivery of therapeutics and use in protein ligand pairs beyond biotin and avidin used for this work.

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

Developing Water–Stable Pore–Partitioned Metal–Organic Frameworks with Multi–Level Symmetry for High–Performance Sorption Applications

Here a new perspective is proposed in the design of pore-space-partitioned MOFs that is focused on ligand symmetry properties sub-divided here into three hierarchical levels: 1) overall ligand, 2) ligand substructure such as backbone or core, and 3) the substituent groups. Different combinations of the above symmetry properties exist. Given the close correlation between nature of chemical moiety and its symmetry, such a unique perspective into ligand symmetry and sub-symmetry in MOF design translates into the influences on MOF properties. Five new MOFs have been prepared that exhibit excellent hydrothermal stability and high-performance adsorption properties with potential applications such as C 3 H 6 /C 2 H 4 and C 2 H 2 /CO 2 selective adsorption. The combination of high stability with high benzene/cyclohexane selectivity of ≈13.7 is also of particular interest.

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

Controlling Extraction of Rare Earth Elements Using Functionalized Aryl-vinyl Phosphonic Acid Esters

Ligands that can discriminate between individual rare earth elements are important for production of these critical elements. A set of aryl-vinyl phosphonic acid ligands for extracting rare earth elements were designed and synthesized under the hypothesis that the strength of the rare earth-ligand interactions could be tuned by changing the dipole moment of the ligand. The ligands were synthesized via a two-step reaction procedure using a Heck coupling reaction to functionalize vinyl phosphonic acid, followed by Steglich esterification to obtain high-purity styryl phosphonic acid monoesters with varying dipole moments along the P-C bond. The metal binding strength and composition of the rare earth complexes formed with these styryl phosphonic acid monoesters were experimentally studied by liquid-liquid extraction techniques, while DFT calculations were performed to determine the dipole moments of the free and complexed ligands and the electronic structure of the complexes formed. All three prepared ligands were much stronger extracting agents for europium(III) than the dialkylphosphonic acids usually used for this separation. However, the order of increasing extraction strength was found to match the order of the decreasing calculated dipole moment along the P-C bond of the three styryl-based ligands, rather than correlating with increasing ligand basicity, as reflected by the pK a of the ligands. Finally, these findings suggest that this approach can be used to systematically alter the extraction strength of aromatic phosphonic monoesters for rare earth element purification.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2021

Selective Photoswitchable Allosteric Agonist of a G Protein-Coupled Receptor

G protein-coupled receptors (GPCRs) are the most common targets of drug discovery. However, the similarity between related GPCRs combined with the complex spatiotemporal dynamics of receptor activation in vivo has hindered drug development. Photopharmacology offers the possibility of using light to control the location and timing of drug action by incorporating a photoisomerizable azobenzene into a GPCR ligand, enabling rapid and reversible switching between an inactive and active configuration. Recent advances in this area include (i) photoagonists and photoantagonists that directly control receptor activity but are nonselective because they bind conserved sites, and (ii) photoallosteric modulators that bind selectively to nonconserved sites but indirectly control receptor activity by modulating the response to endogenous ligand. In this study, we designed a photoswitchable allosteric agonist that targets a nonconserved allosteric site for selectivity and activates the receptor on its own to provide direct control. This work culminated in the development of aBINA, a photoswitchable allosteric agonist that selectively activates the G i/o -coupled metabotropic glutamate receptor 2 (mGluR2). aBINA is the first example of a new class of precision drugs for GPCRs and other clinically important signaling proteins.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2026

A family portrait of lanmodulin selectivity for enhanced rare-earth separations

Proteins offer a molecular design space to create bespoke ligands for the separation of critical metals like rare earth elements (REs). However, data-intensive approaches to tune metalloprotein selectivity are constrained by the low-throughput nature of existing characterization methods. Here we invented an assay called ‘SpyTag-Catcher Immobilization of Lanmodulin for Assaying Metal-Binding Selectivity’ (SpyCI-LAMBS) to measure metalloprotein selectivity en masse. This 96-format workflow was used to study the selectivity of 621 lanmodulin (LanM) orthologs for 15 REs, revealing eight distinct selectivity profiles based on sequence-to-function analyses. We discovered >200 LanMs with stronger selectivity against low-value LaIII relative to the prototypical LanM. This includes a LanM that can perform a challenging one-stage separation of PrIII from LaIII with up to >99.9 mol% purity and 83% yield. SpyCI-LAMBS is a powerful tool that can rapidly collect high-fidelity selectivity data to inform metal ion separations and machine-learning-assisted metalloprotein design.

59 BASIC BIOLOGICAL SCIENCES↗
DOE OSTI2026

Selective CO 2 Reduction by Bis(bipyridine)cobalt(II) Catalysts: The Role of Pendant Pyridine as a Proton Acceptor

Electrochemical CO 2 reduction reaction (CO 2 RR) catalyzed by molecular earth-abundant metal catalysts is a promising strategy to convert CO 2 into value-added products. One recent trend in this field has been focusing on the rational design of catalysts by incorporating redox-active ligands and modifying the secondary coordination sphere (SCS) to achieve efficient and selective CO 2 RR. Herein, we report a series of Co bis­(bipyridine) catalysts featuring various dangling groups, such as pyridine, tertiary amine, or butyl, in the secondary coordination sphere (Co-PyMe, Co-Py, Co-PrN, and Co-Bu). Efficient, selective electrocatalytic CO 2 RR was achieved by the complexes after the generation of triply reduced intermediate consisting of a Co I center and a dianionic ligand, producing CO as the major product and trace amount of H 2 . Strong correlations with the identity of dangling groups and turnover frequency (TOF) have been observed, in which Co-PyMe displayed the highest TOF (1086 s –1 in MeCN/H 2 O). Mechanistic studies indicated that the acceleration of CO 2 RR with pyridine-functionalized catalysts were derived from the protonation of pyridine dangling groups which participated as weak acids in the H-bonding network with exogenous proton sources, stabilizing CO 2 -bound intermediates and facilitating proton transfer. In addition, precatalytic CO 2 binding and activation at the third reduction (−2.1 V) was revealed by CV and SEC-IR studies. The resultant doubly reduced CO-bound species acted as a trapping state which inhibited CO 2 RR electrocatalysis. Regeneration of active species was accessed via reductive dissociation of CO at a more negative potential. In conclusion, this study highlights the combined effects of redox-active ligands and pyridine/pyridinium as SCS groups on CO 2 RR catalysis and provides design principles for future development of CO 2 RR catalysts utilizing pyridine/pyridiniums as SCS functional groups to fine-tune the catalytic activity.

CO2 reduction↗
DOE OSTI2025

Surface Carboxylate Sensitivity to Electron and Hole Relaxation in Photoexcited Cadmium Sulfide Nanocrystals

Understanding how passivating surface ligands couple to excitonic states in nanocrystal photocatalysts is crucial for controlling nonradiative relaxation pathways which compete with interfacial charge transfer. Here, we report femtosecond transient infrared (IR) spectroscopy to resolve ∼100 fs ligand-exciton coupling between 1S exciton states in oleate-capped cadmium sulfide (CdS) nanocrystals and vibrational modes of surface carboxylates. Differential mid-IR spectra show distinct negative amplitude and positive photoinduced absorption signals at ∼1540 cm –1 (carboxylate asymmetric stretch) and ∼1440 cm –1 (carboxylate symmetric stretch), respectively. Fluence-dependent transient IR measurements reveal that the symmetric stretch is uniquely sensitive to picosecond Auger recombination, while the asymmetric stretch shows no analogous decay. Our results provide direct measurement of femtosecond ligand-exciton coupling in CdS nanocrystals and demonstrate how surface-bound carboxylate ligands serve as carrier-specific reporters of nanocrystal photophysics. Furthermore, these findings offer critical insights for designing and developing predictive models for ligand-mediated strategies in next-generation nanocrystal photocatalysts.

Cadmium sulfide↗
NASA NTRS2002

Regulation of collagenase-3 and osteocalcin gene expression by collagen and osteopontin in differentiating MC3T3-E1 cells

Both collagenase-3 and osteocalcin mRNAs are expressed maximally during the later stages of osteoblast differentiation. Here, we demonstrate that collagenase-3 mRNA expression in differentiating MC3T3-E1 cells is dependent upon the presence of ascorbic acid, is inhibited in the presence of the collagen synthesis inhibitor, 3,4-dehydroproline, and is stimulated by growth on collagen in the absence of ascorbic acid. Transient transfection studies show that collagenase-3 promoter activity increases during cell differentiation and requires the presence of ascorbic acid. Additionally, we show that, in differentiating MC3T3-E1 cells, collagenase-3 gene expression increases in the presence of an anti-osteopontin monoclonal antibody that binds near the RGD motif of this protein, whereas osteocalcin expression is inhibited. Furthermore, an RGD peptidomimetic compound, designed to block interaction of ligands to the alpha(v) integrin subunit, increases osteocalcin expression and inhibits collagenase-3 expression, suggesting that the RGD peptidomimetic initiates certain alpha(v) integrin signaling in osteoblastic cells. Overall, these studies demonstrate that stimulation of collagenase-3 expression during osteoblast differentiation requires synthesis of a collagenous matrix and that osteopontin and alpha(v) integrins exert divergent regulation of collagenase-3 and osteocalcin expression during osteoblast differentiation.

NASA Discipline Musculoskeletal↗
DOE OSTI2020

Controlling Metal–Organic Framework/ZnO Heterostructure Kinetics through Selective Ligand Binding to ZnO Surface Steps

Metal–organic framework (MOF) heterostructures exhibit unique properties beyond those of individual components, but their design requires an understanding of energetic and kinetic controls at MOF–substrate interfaces. Although the structural relationship has been widely used in heterostructure design, it overlooks the interplay between the organic ligand and the substrate which controls the kinetics and energetics of growth of the final structure. In this study, we used zeolitic imidazolate frameworks (ZIF-8) on ZnO as a model system to evaluate this interplay via in situ monitoring and simulations. Our results demonstrate multiple roles of the 2-methyl-imidazole (2-MIM) ligand as “dissolution-promoter”, “step-pinner”, and “terrace-binder” on the ZnO (001) face and “dissolution-promoter” and “terrace-binder” on the ZnO (100) face. Through these multiple face-specific roles, 2-MIM modulates ZnO dissolution kinetics and, hence, the Zn 2+ release rate, tuning local supersaturations that dictating the characteristic ZIF-8 crystallization kinetics on different substrate faces. The critical thickness for transition from 2D to 3D growth is dictated by competition between interfacial and strain energies. The atomic-scale mechanism of the coupled substrate dissolution and MOF growth, mediated by selective linker–substrate binding, furnishes a new synthesis pathway for other complex heterostructures.

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

Hourglass–Shaped Nanocages with Concaved Structures Based on Selective Self–Complementary Coordination Ligands and Tunable Hierarchical Self–Assembly

Three-dimensional (3D) structures constructed via coordination-driven self-assemblies have recently garnered increasing attention due to the challenges in structural design and potential applications. In particular, developing new strategy for the convenient and precise self-assemblies of 3D supramolecular structures is of utmost interest. Introducing the concept of self-coordination ligands, herein the design and synthesis of two meta-modified terpyridyl ligands with selective self-complementary coordination moiety are reported and their capability to assemble into two hourglass-shaped nanocages SA and SB is demonstrated. Within these 3D structures, the meta-modified terpyridyl unit preferably coordinates with itself to serve as concave part. By changing the arm length of the ligands, hexamer (SA) and tetramer (SB) are obtained respectively. In-depth studies on the assembly mechanism of SA and SB indicate that the dimers could be formed first via self-complementary coordination and play crucial roles in controlling the final structures. Moreover, both SA and SB can go through hierarchical self-assemblies in solution as well as on solid–liquid interface, which are characterized by transmission electron microscope (TEM) and scanning tunneling microscopy (STM). As a result, it is further demonstrated that various higher-order assembly structures can be achieved by tuning the environmental conditions.

3D metallo-supramolecules↗
DOE OSTI2025

Computational design of highly signalling-active membrane receptors through solvent-mediated allosteric networks

Abstract Protein catalysis and allostery require the atomic-level orchestration and motion of residues and ligand, solvent and protein effector molecules. However, the ability to design protein activity through precise protein–solvent cooperative interactions has not yet been demonstrated. Here we report the design of 14 membrane receptors that catalyse G protein nucleotide exchange through diverse engineered allosteric pathways mediated by cooperative networks of intraprotein, protein–ligand and –solvent molecule interactions. Consistent with predictions, the designed protein activities correlated well with the level of plasticity of the networks at flexible transmembrane helical interfaces. Several designs displayed considerably enhanced thermostability and activity compared with related natural receptors. The most stable and active variant crystallized in an unforeseen signalling-active conformation, in excellent agreement with the design models. The allosteric network topologies of the best designs bear limited similarity to those of natural receptors and reveal an allosteric interaction space larger than previously inferred from natural proteins. The approach should prove useful for engineering proteins with novel complex protein binding, catalytic and signalling activities.

Chemistry↗
DOE OSTI2021

Single-Site Metal Organic Complexes on Oxide Supports for Selective Alkane Functionalization

High levels of reaction selectivity for heterogeneous catalysis are generally difficult to achieve with traditional metal nanoparticle catalysts, due to the variety of metal binding sites available. In this project, we have developed a metal-ligand coordination strategy to form transition metal single-sites on high surface area supports as heterogeneous single-site catalysts. Metal centers can be atomically dispersed in the binding pockets of organic ligands on oxide supports. The systems have to be carefully designed so that tendencies for metal cluster formation or binding to surface defect sites are overcome by the attractive coordination environment provided by the organic ligand. This was confirmed by a comprehensive set of characterization methods, including XAS, XPS, XRD, TEM, and CO adsorption. Design and tuning of metal-support and support-ligand interactions were crucial for high structural uniformity. We demonstrate that supported metal-ligand SSCs are effective, recyclable catalysts for alkene hydrosilylation reactions. Compared with commercial homogeneous catalysts, they exhibit improved yield and selectivity, less metal aggregation and side reactions, and stronger tolerance with functionalized substrates. These results give some preliminary indication that coordination with organic ligands can improve activity and selectivity in metal/oxide heterogeneous catalysts.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2020

Tunable magnetic order in low-symmetry SeO 3 ligand linked TM 3 (SeO 3 ) 3 H 2 O ( TM =Mn , Co, and Ni) compounds

The ability to design crystal lattices with specific sublattice geometries has long been sought after especially in the context of harnessing magnetic frustration to elicit emergent physics. One approach which has seen some success recently is to design magnetic sublattices chemically through the use of nonmagnetic linker ligands as scaffolding for the magnetic ions. In this work we report the magnetic properties of one such family of materials, the transition metal (TM) selenite hydrates with chemical formula TM 3 (SeO 3 ) 3 H 2 O. These materials link highly distorted TMO 6 octahedra via nonmagnetic [SeO 3 ] 2+ linkers. Studying members with TM = Mn, Co, and Ni we use magnetic susceptibility and neutron powder diffraction to identify antiferromagnetic order in all three compounds with moderate frustration indexes. A comparison of the magnetic structures suggests that while the overall structure of the SeO 3 scaffolding remains unchanged the TM effects changes in the magnetic properties through tuning the internal bonding parameters and the single-ion physics. Changing from Mn to Co is found to be particularly consequential manifesting changes in both the ordered-moment direction and in the direction of the ordering vector. Field-dependent measurements of the susceptibility and heat capacity reveal metamagnetic transitions in both Mn 3 (SeO 3 ) 3 H 2 O and Co 3 (SeO 3 ) 3 H 2 O indicating nearby magnetic ground states accessible under relatively small applied fields. Density functional theory calculations broadly confirm these results, showing both a sensitivity of the magnetic structure to the TM and its local environment. Although no spin liquid behavior is achieved, these results suggest the fruitfulness of such synthesis philosophies and encourage future work to engender higher frustration in these materials via doping, field, pressure, or larger linker ligands.

36 MATERIALS SCIENCE↗