Engineering Papers⌕ Search

SEARCH · Engineering Papers

Results for “COMPLEXITY”

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 1,639 records · Page 91
All sourcesNASA NTRSDOE OSTI
DOE OSTI2025

Synthesis and Characterization of Homo- and Heteroleptic Neptunium(IV) Heteroarylalkenolate Complexes

Heteroleptic An IV (An = U, Np) chlorido-ketoenaminate complexes of the type [AnCl 2 (TFB-tBuA) 2 (THF)] (An-1 type: U-1, Np-1; TFB-tBuA = 4-(tertbutylamino)- 1,1,1-trifluorobut-3-en-2-one) and the homoleptic Np IV heteroarylalkenolate complexes [Np(PyTFP) 4 ] (Np-2, PyTFP = 1-(pyridin-2-yl)-3,3,3-trifluoroprop- 1-en-2-ol) and [Np(DMOTFP) 4 ] (Np-3, DMOTFP = 1-(4,5-dimethyloxazol- 2-yl)-3,3,3-trifluoroprop-1-en-2-ol) were synthesized and characterized (SC-XRD, NMR, Vis-NIR, MS). While their solid-state structures compare well to those of their uranium analogues, the behavior in solution showed significant differences. The binding motif of the DMOTFP ligand in complex Np-3 can change to form two different complex isomers, as seen by paramagnetic chemical shifts in NMR experiments. Furthermore, the flexibility and the influence of the steric effects at the N-side of the ligands are discussed and compared with its uranium counterpart.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2015

Lanthanide(III) di- and tetra-nuclear complexes supported by a chelating tripodal tris(amidate) ligand

Syntheses, structural, and spectroscopic characterization of multinuclear tris(amidate) lanthanide complexes is described. Addition of K 3 [N(o-PhNC(O) t Bu) 3 ] to LnX 3 (LnX 3 = LaBr 3 , CeI 3 , and NdCl 3 ) in N,N-dimethylformamide (DMF) results in the generation of dinuclear complexes, [Ln(N(o-PhNC(O) t Bu) 3 )(DMF)] 2 (μ-DMF) (Ln = La (1), Ce (2), Nd(3)), in good yields. Syntheses of tetranuclear complexes, [Ln(N(o-PhNC(O) t Bu) 3 )] 4 (Ln = Ce (4), Nd(5)), resulted from protonolysis of Ln[N(SiMe 3 ) 2 ] 3 (Ln = Ce, Nd) with N(o-PhNCH(O) t Bu) 3 . As a result, in the solid-state, complexes 1–5 exhibit coordination modes of the tripodal tris(amidate) ligand that are unique to the 4f elements and have not been previously observed in transition metal systems.

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

Strontium Tris(cyclopentadienyl) Complexes: Isostructural f0/d0 Analogues of Divalent Lanthanides

Isostructural, diamagnetic diluents are commonly used in magnetic investigations to eliminate interactions between neighboring electron spins. For divalent lanthanides, these diluents are currently limited to closed-shell ytterbium(II) complexes; ytterbium(II), however, is a poor size-match for the large early- and mid-lanthanides, precluding access to certain ligand frameworks. To aid in the study of lanthanide(II) complexes with unconventional electronic structures and magnetic properties, three strontium tris-cyclopentadienyl complexes, [K(2.2.2-cryptand)][SrCpR3], with common substituted cyclopentadienyl ligands, CpR = C5Me4H (Cptet), C5H4(SiMe3) (Cp'), and C5H3(SiMe3)2 (Cp″) were synthesized, characterized, and examined as diamagnetic diluents. En route to their synthesis, two new Sr metallocenes, [SrCpR2] CpR = Cptet, Cp', were also prepared. [K(2.2.2-cryptand)][SrCptet3] was used to dilute the new complex [K(2.2.2-cryptand)][EuIICptet3], and the EPR spectra of the diluted material shows narrower linewidths than those of pure [K(2.2.2-cryptand)][EuIICptet3], suggesting an increase in the spin-spin relaxation time that enables determination of the europium hyperfine coupling constant.

Zlotnikov, Samuel B↗
DOE OSTI2025

Spectroscopic and Theoretical Studies of Ruthenium Complexes with a Noninnocent N 2 S 2 Ligand in Different Redox States

Herein we report an electronic structure investigation of neutral and oxidized Ru complexes containing a redox noninnocent N 2 S 2 ligand derived from o-phenylenediamide (L1). UV–vis spectroelectrochemistry (SEC) studies were conducted on the square pyramidal complex [Ru I I(L1)(PPh 3 )] (1) and the six-coordinate complexes [Ru I I(μ-BH 3 )(L1)(PPh 3 )] (2) – which has BH 3 bound in a metal–ligand cooperative (MLC) fashion across Ru and L1 – and [Ru II (L1)(PPh 3 )(MeCN)] (3). The SEC results yielded spectra assigned to singly and doubly oxidized 1 and 3, revealing electronic structure changes as a function of oxidation state and in response to the presence and absence of bound MeCN. By contrast, the SEC results of 2 showed that it rapidly loses MLC-bound BH 3 upon oxidation. The SEC results for 1 and 3 were compared to single-crystal XRD data and UV–vis, EPR, and P K-edge, S K-edge, and Ru L 3 -edge X-ray absorption spectroscopy (XAS) data collected on isolated samples of chemically oxidized 3. The data revealed that the first two oxidations are primarily localized on the ligand, which was supported by DFT and TDDFT calculations. DFT calculations for the doubly oxidized species revealed a singlet ground state with a singlet–triplet gap of 8.9 kcal/mol. CASPT2 calculations corroborated the DFT calculations and further revealed that the singlet ground state is multiconfigurational with 21% radical character. Collectively, the results establish redox formalisms and the underlying electronic structure of Ru complexes containing a noninnocent tetradentate ligand in different oxidation states.

electronic structure↗
DOE OSTI2025

Structural and Spectroscopic Characterization of Plutonium and Other Tetravalent Metals Complexed to a Keggin Ion

Here, we report the isolation of the first plutonium(IV) complex with a Keggin ion chelator: Cs 20 [Pu(PW 11 O 39 ) 2 ] 2 ·13H 2 O. Single crystal XRD and solid-state UV–vis absorbance analysis demonstrate the stabilization of Pu 4+ by the Keggin ligand. The unit cell contains two [Pu(PW 11 O 39 ) 2 ] 10– complexes (Pu(PW 11 ) 2 ) bridged by Cs + . Raman and 31 P NMR spectra of Pu(PW 11 ) 2 are consistent with the analogous Zr 4+ , Hf 4+ , Ce 4+ , and Th 4+ complexes. The Pu–O bond distances at the two Pu sites are 2.35(3) and 2.34(3) Å, matching the value extrapolated from the bonding trend built with the other 8-coordinated tetravalent cations. However, the long-range arrangement of the Pu(PW 11 ) 2 complexes within the lattice is unique in the series of M IV (PW 11 ) 2 compounds: pairs of Pu(PW 11 ) 2 are organized perpendicular to each other. Based on solution-state UV–visible absorbance, small-angle X-ray scattering (SAXS), and 31 P NMR, the tetravalent cations quantitatively form the 1:2 species in solution ([Pu(PW 11 O 39 ) 2 ] 10– (aq) ) and no 1:1 species ([Pu(PW 11 O 39 )(H 2 O) x ] 3– (aq) ). Finally, a linear correlation exists between the metal–oxygen distances in the M IV (PW 11 ) 2 compounds and the corresponding metal dioxides, allowing for extrapolation for Pa 4+ , Am 4+ , and Bk 4+ . The results indicate that our microscale POM approach represents a viable pathway to probe properties of rare actinide ions in discrete molecules, beyond the traditional oxide extended solids.

and nuclear chemistry↗
DOE OSTI2016

Heptavalent Neptunium in a Gas-Phase Complex: (Np VII O 3 + )(NO 3 – ) 2

A central goal of chemistry is to achieve ultimate oxidation states, including in gas-phase complexes with no condensed phase perturbations. In the case of the actinide elements, the highest established oxidation states are labile Pu(VII) and somewhat more stable Np(VII). We have synthesized and characterized gas-phase AnO 3 (NO 3 ) 2 - complexes for An = U, Np, and Pu by endothermic NO 2 elimination from AnO 2 (NO 3 ) 3 -. It was previously demonstrated that the PuO 3 + core of PuO 3 (NO 3 ) 2 - has a Pu—O• radical bond such that the oxidation state is Pu(VI); it follows that in UO 3 (NO 3 ) 2 - it is the stable U(VI) oxidation state. On the basis of the relatively more facile synthesis of NpO 3 (NO 3 ) 2 -, a Np(VII) oxidation state is inferred. This interpretation is substantiated by reactivity of the three complexes: NO 2 spontaneously adds to UO 3 (NO 3 ) 2 - and PuO 3 (NO 3 ) 2 - but not to NpO 3 (NO 3 ) 2 -. This unreactive character is attributed to a Np(VII)O 3 + core with three stable Np=O bonds, this in contrast to reactive U—O• and Pu—O• radical bonds. The computed structures and reaction energies for the three AnO 3 (NO 3 ) 2 - support the conclusion that the oxidation states are U(VI), Np(VII), and Pu(VI). These results establish the extreme Np(VII) oxidation state in a gas-phase complex, and demonstrate the inherently greater stability of Np(VII) versus Pu(VII).

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2017

Electrochemical Reduction of CO 2 Catalyzed by Re(pyridine-oxazoline)(CO) 3 Cl Complexes

In a series of rhenium tricarbonyl complexes coordinated by asymmetric diimine ligands containing a pyridine moiety bound to an oxazoline ring were synthesized, structurally and electrochemically characterized, and screened for CO 2 reduction ability. We reported complexes are of the type Re(N-N)(CO) 3 Cl, with N-N = 2-(pyridin-2-yl)-4,5-dihydrooxazole (1), 5-methyl-2-(pyridin-2-yl)-4,5-dihydrooxazole (2), and 5-phenyl-2-(pyridin-2-yl)-4,5-dihydrooxazole (3). The electrocatalytic reduction of CO 2 by these complexes was observed in a variety of solvents and proceeds more quickly in acetonitrile than in dimethylformamide (DMF) and dimethyl sulfoxide (DMSO). The analysis of the catalytic cycle for electrochemical CO 2 reduction by 1 in acetonitrile using density functional theory (DFT) supports the C–O bond cleavage step being the rate-determining step (RDS) (ΔG ‡ = 27.2 kcal mol –1 ). Furthermore, the dependency of the turnover frequencies (TOFs) on the donor number (DN) of the solvent also supports that C–O bond cleavage is the rate-determining step. Moreover, the calculations using explicit solvent molecules indicate that the solvent dependence likely arises from a protonation-first mechanism. Unlike other complexes derived from fac-Re(bpy)(CO) 3 Cl (I; bpy = 2,2'-bipyridine), in which one of the pyridyl moieties in the bpy ligand is replaced by another imine, no catalytic enhancement occurs during the first reduction potential. Remarkably, catalysts 1 and 2 display relative turnover frequencies, (i cat /i p ) 2 , up to 7 times larger than that of I.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2017

Laser initiation of Fe(II) complexes of 4-nitro-pyrazolyl substituted tetrazine ligands

Here, the synthesis and characterization of new 1,2,4-triazolyl and 4-nitro-pyrazolyl substituted tetrazine ligands has been achieved. The strongly electron deficient 1,2,4-triazolyl substituted ligands did not coordinate Fe(II) metal centers, while the mildly electron deficient 4-nitro-pyrazolyl substituted ligands did coordinate Fe(II) metal centers in a 2:1 ratio of ligand to metal. The thermal stability and mechanical sensitivity characteristics of the complexes are similar to the conventional explosive pentaerythritol tetranitrate. The complexes had strong absorption in the visible region of the spectrum that extended into the near-infrared. In spite of having improved oxygen balances, increased mechanical sensitivity, and similar absorption of NIR light to recently reported Fe(II) tetrazine complexes, these newly synthesized explosives were more difficult to initiate with Nd:YAG pulsed laser light. More specifically, the complexes required lower densities (0.9 g/cm 3 ) to initiate at the same threshold utilized to initiate previous materials at higher densities (1.05 g/cm 3 ).

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2018

η 2 -SO 2 Linkage Photoisomer of an Osmium Coordination Complex

We report the discovery of an n 2 -SO 2 linkage photoisomer in the osmium pentaammine coordination complex, [Os(NH 3 ) 5 (SO 2 )][Os(NH 3 ) 5 (SO 3 )]Cl 4 (1). Its dark and light-induced crystal structures are determined via synchrotron X-ray crystallography, at 100K, where the photo-induced state is metastable in a single crystal that has been stimulated by 505 nm light for 2.5 hrs. The SO 2 photoisomer in the [Os(NH 3 ) 5 (SO 2 )] 2+ cation contrasts starkly with the photo-inactivity of the SO 3 ligand in its companion [Os(NH 3 ) 5 (SO 3 )] 2+ cation within the crystallographic asymmetric unit of this single crystal. Panchromatic optical absorption characteristics of this single crystal are revealed in both dark and light-induced states, using concerted absorption spectroscopy and optical microscopy. Its optical absorption halves across most of its visible spectrum, upon exposure to 505nm light. The SO 2 ligand seems to be responsible for this photo-induced bleaching effect, judging from a comparison of the dark and light-induced crystal structures of 1. The SO 2 linkage photo-isomerism is found to be thermally reversible and so this complex presents a rare example of an osmium-based solid-state optical switch. Such switching in an osmium-based complex is significant be-cause bottom-row transition metals stand to offer linkage photo-isomerism with the greatest photo-conversion levels and thermal stability. Furthermore, the demonstration of n 2 -SO 2 bonding in this complex also represents a fundamental contribution to osmium coordination chemistry

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2018

A Pseudotetrahedral Uranium(V) Complex

A series of uranium amides were synthesized from N,N,N-cyclohexyl(trimethylsilyl)lithium amide [Li][N(TMS)Cy] and uranium tetrachloride to give U(NCySiMe 3 ) x (Cl) 4–x , where x = 2, 3, or 4. The diamide was then isolated as a bimetallic, bridging lithium chloride adduct ((UCl 2 (NCyTMS) 2 ) 2 -LiCl(THF) 2 ), and the tris(amide) was isolated as the lithium chloride adduct of the monometallic species (UCl(NCyTMS) 3 -LiCl(THF) 2 ). The tetraamide complex was isolated as the four-coordinate pseudotetrahedron. Cyclic voltammetry revealed an easily accessible reversible oxidation wave, and upon chemical oxidation, the U V amido cation was isolated in near-quantitative yields. The synthesis of this family of compounds allows a direct comparison of the electronic structure and properties of isostructural U IV and U V tetraamide complexes. Spectroscopic investigations consisting of UV–vis, NIR, MCD, EPR, and U L 3 -edge XANES, along with density functional and wave function calculations, of the four-coordinate U IV and U V complexes have been used to understand the electronic structure of these pseudotetrahedral complexes.

38 RADIATION CHEMISTRY, RADIOCHEMISTRY, AND NUCLEA↗
DOE OSTI2018

Bond Covalency and Oxidation State of Actinide Ions Complexed with Therapeutic Chelating Agent 3,4,3-LI(1,2-HOPO)

The hydroxypyridinone ligand 3,4,3-LI(1,2-HOPO) is a promising agent for biological decorporation of radionuclides, and allows spectroscopic detection of many lanthanide (Ln) and actinide (An) species via sensitized luminescence. Despite the manifest uses of this ligand, the structural and thermodynamic properties of its complexes across the An series remain understudied. Theoretical investigations of the binding of An(III) and An(IV) ions, from actinium to einsteinium, by the 3,4,3-LI(1,2-HOPO) ligand, as well as experimental extended X-ray absorption fine structure (EXAFS) studies on the trivalent americium, curium, and californium complexes were employed in this paper to address the resulting structures, thermodynamic parameters, redox properties, and corresponding electronic configurations. An(IV) ions were found to form much stronger complexes than An(III) ions, consistent with experimental measurements. Complexation of both An(III) and An(IV) ions generally becomes more favorable for heavier actinides, reflecting increased energy degeneracy driven covalency and concomitant orbital mixing between the 5f orbitals of the An ions and the π orbitals of the ligand. Finally and notably, the ability of this ligand to either accept or donate electron density as needed from its pyridine rings is found to be key to its extraordinary stability across the actinide series.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2018

Solution Thermodynamics and Kinetics of Metal Complexation with a Hydroxypyridinone Chelator Designed for Thorium-227 Targeted Alpha Therapy

In this study, the solution chemistry of a chelator developed for 227 Th targeted alpha therapy was probed. The compound of interest is an octadentate ligand comprising four N-methyl-3-hydroxy-pyridine-2-one metal-binding units, two tertiary amine groups, and one carboxylate arm appended for bioconjugation. The seven pK a values of the ligand and the stability constants of complexes formed with Th(IV), Hf(IV), Zr(IV), Gd(III), Eu(III), Al(III), and Fe(III) were determined. The ligand exhibits extreme thermodynamic selectivity toward tetravalent metal ions with a ca. 20 orders of magnitude difference between the formation constant of the Th(IV) species formed at physiological pH, namely [ThL] - , and that of its Eu(III) analogue. Likewise, log β 110 values of 41.7 ± 0.3 and 26.9 ± 0.3 (T = 25 °C) were measured for [ThL] - and [Fe III L] 2- , respectively, highlighting the high affinity and selectivity of the ligand for Th ions over potentially competing endogenous metals. Single crystal X-ray analysis of the Fe(III) complex revealed a dinuclear 2:2 metal:chelator complex crystallizing in the space group P1 - . The formation of this dimeric species is likely favored by several intramolecular hydrogen bonds and the protonation state of the chelator in acidic media. L III edge EXAFS data on the Th(IV) complexes of both the ligand and a monoclonal antibody conjugate revealed the expected mononuclear 1:1 metal:chelator coordination environment. This was also confirmed by high resolution mass spectrometry. Lastly, kinetic experiments demonstrated that labeling the bioconjugated ligand with Th(IV) could be achieved and completed after 1 h at room temperature, reinforcing the high suitability of this chelator for 227 Th targeted alpha therapy.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2018

Assessing the Metal–Metal Interactions in a Series of Heterobimetallic Nb/M Complexes (M = Fe, Co, Ni, Cu) and Their Effect on Multielectron Redox Properties

A one-pot synthetic procedure for a series of bimetallic Nb/M complexes, Cl–Nb( i PrNPPh 2 ) 3 M–X (M = Fe (2), Ni (4), Cu (5)), is introduced. A similar procedure aimed at synthesizing a Nb/Co analogue instead affords i PrN=Nb(iPrNPPh 2 ) 2 (μ-PPh 2 )Co–I (3) through cleavage of one phosphinoamide P–N bond under reducing conditions. Complexes 4 and 5 are found to have short Nb-M distances, corresponding to unusual metal–metal bonds between Nb and these first row transition metals. For comparison, a series of heterobimetallic O≡Nb( i PrNPPh 2 ) 3 M–X complexes (M = Fe (7), Co (8), Ni (9), Cu (10)) was synthesized. In these complexes, the Nb V center is engaged in sufficient π-bonding to the terminal oxo ligand to remove the driving force for direct metal–metal interactions. A comparison of the cyclic voltammograms of 2 and 4–10 shows that the presence of a second metal shifts the redox potentials of both Nb and the late metal center anodically, even when direct metal–metal interactions are not present.

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

Comparative Density Functional Theory Study of Magnetic Exchange Couplings in Dinuclear Transition-Metal Complexes

Multicenter transition-metal complexes (MCTMs) with magnetically interacting ions have been proposed as components for information-processing devices and storage units. For any practical application of MCTMs as magnetic units, it is crucial to characterize their magnetic behavior, and in particular, the isotropic magnetic exchange coupling, J, between its magnetic centers. Due to the large size of typical MCTMs, density functional theory is the only practical electronic structure method for evaluating the J coupling. Here, we assess the accuracy of different density functional approximations for predicting the magnetic couplings of eight dinuclear transition-metal complexes, including five dimanganese, two dicopper, and one divanadium with known reliable experimental J couplings spanning from ferromagnetic to strong antiferromagnetic. The density functionals considered include global hybrid functionals which mix semilocal density functional approximations and exact exchange with a fixed admixing parameter, six local hybrid functionals where the admixing parameters are extended to be spatially dependent, the SCAN and r 2 SCAN meta-generalized gradient approximations (GGAs), and two widely used GGAs. We found that global hybrids tested in this work have a tendency to over-correct the error in magnetic coupling parameters from the Perdew–Burke–Ernzerhof (PBE) GGA as seen for manganese complexes. The performance of local hybrid density functionals shows no improvement in terms of bias and is scattered without a clear trend, suggesting that more efforts are needed for the extension from global to local hybrid density functionals for this particular property. The SCAN and r 2 SCAN meta-GGAs are found to perform as well as benchmark global hybrids on most tested complexes. We further analyze the charge density redistribution of meta-GGAs as well as global and local hybrid density functionals with respect to that of PBE, in connection to the self-interaction error or delocalization error.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2024

Importance of Electron Correlation on the Geometry and Electronic Structure of [2Fe–2S] Systems: A Benchmark Study of the [Fe 2 S 2 (SCH 3 ) 4 ] 2–,3–,4– , [Fe 2 S 2 (SCys) 4 ] 2– , [Fe 2 S 2 (S- p -tol) 4 ] 2– , and [Fe 2 S 2 (S- o -xyl) 4 ] 2– Complexes

Iron–sulfur clusters are crucial for biological electron transport and catalysis. Obtaining accurate geometries, energetics, manifolds of their excited electronic states, and reduction energies is important to understand their role in these processes. Here, using a [2Fe–2S] model complex with Fe II and Fe III oxidation states, which leads to different charges, i.e., [Fe 2 S 2 (SMe) 4 ] 2–,3–,4– , we benchmarked a variety of computational methodologies ranging from density functional theory (DFT) to post-Hartree–Fock methods, including complete active space self-consistent field (CASSCF), multireference configuration interaction, the second-order N-electron valence state perturbation theory (NEVPT2), and the linearized integrand approximation of adiabatic connection (AC0) approaches. Additionally, we studied three experimentally well-characterized complexes, [Fe 2 S 2 (SCys) 4 ] 2– , [Fe 2 S 2 (S-o-tol) 4 ] 2– , and [Fe 2 S 2 (S-o-xyl) 4 ] 2– , via DFT methods. We conclude that the dynamic electron correlation is important for accurately predicting the geometry of these complexes. Broken symmetry (BS) DFT correctly predicts experimental geometries of low-spin multiplicity, while CASSCF does not. However, BS-DFT significantly overestimates the difference between the low- and high-spin electronic states for a given oxidation state. At the same time, CASSCF underestimates it but provides relative energies closer to the reference NEVPT2 results. Finally, AC0 provides energetics of NEVPT2 quality with the additional advantage of being able to use large CASSCF sizes. NEVPT2 gives the best estimates of the Fe III /Fe III → Fe II /Fe III (4.27 eV) and Fe II /F III → Fe II /F II (7.72 eV) reduction energies. The results provide insight into the electronic structure of these complexes and assist in the understanding of their physical properties.

37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CH↗
DOE OSTI2019

CHARMM-GUI Membrane Builder for Complex Biological Membrane Simulations with Glycolipids and Lipoglycans

Glycolipids (such as glycoglycerolipids, glycosphingolipids, and glycosylphosphatidylinositol) and lipoglycans (such as lipopolysaccharides (LPS), lipooligosaccharides (LOS), mycobacterial lipoarabinomannan, and mycoplasma lipoglycans) are typically found on the surface of cell membranes and play crucial roles in various cellular functions. Characterizing their structure and dynamics at the molecular level is essential to understand their biological roles, but systematic generation of glycolipid and lipoglycan structures is challenging because of great variations in lipid structures and glycan sequences (i.e., carbohydrate types and their linkages). To facilitate the generation of all-atom glycolipid/LPS/LOS structures, we have developed Glycolipid Modeler and LPS Modeler in CHARMM-GUI (http://www.charmm-gui.org), a web-based interface that simplifies building of complex biological simulation systems. In addition, we have incorporated these modules into Membrane Builder so that users can readily build a complex symmetric or asymmetric biological membrane system with various glycolipids and LPS/LOS. These tools are expected to be useful in innovative and novel glycolipid/LPS/LOS modeling and simulation research by easing tedious and intricate steps in modeling complex biological systems and shall provide insight into structures, dynamics, and underlying mechanisms of complex glycolipid-/LPS-/LOS-containing biological membrane systems.

Lee, Jumin↗
DOE OSTI2015

Rational Design of Orthogonal Multipolar Interactions with Fluorine in Protein–Ligand Complexes

Multipolar interactions involving fluorine and the protein backbone have been frequently observed in protein–ligand complexes. Such fluorine–backbone interactions may substantially contribute to the high affinity of small molecule inhibitors. Here we found that introduction of trifluoromethyl groups into two different sites in the thienopyrimidine class of menin–MLL inhibitors considerably improved their inhibitory activity. In both cases, trifluoromethyl groups are engaged in short interactions with the backbone of menin. In order to understand the effect of fluorine, we synthesized a series of analogues by systematically changing the number of fluorine atoms, and we determined high-resolution crystal structures of the complexes with menin. Here, we found that introduction of fluorine at favorable geometry for interactions with backbone carbonyls may improve the activity of menin–MLL inhibitors as much as 5- to 10-fold. In order to facilitate the design of multipolar fluorine–backbone interactions in protein–ligand complexes, we developed a computational algorithm named FMAP, which calculates fluorophilic sites in proximity to the protein backbone. We demonstrated that FMAP could be used to rationalize improvement in the activity of known protein inhibitors upon introduction of fluorine. Furthermore, FMAP may also represent a valuable tool for designing new fluorine substitutions and support ligand optimization in drug discovery projects. Analysis of the menin–MLL inhibitor complexes revealed that the backbone in secondary structures is particularly accessible to the interactions with fluorine. Lastly, considering that secondary structure elements are frequently exposed at protein interfaces, we postulate that multipolar fluorine–backbone interactions may represent a particularly attractive approach to improve inhibitors of protein–protein interactions.

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

Toward Full Configuration Interaction for Transition-Metal Complexes

In this work, an efficacious approximation to full configuration interaction (FCI) is adapted to calculate singlet-triplet gaps for transition-metal complexes. This strategy, incremental FCI (iFCI), uses a many-body expansion to systematically add correlation to a simple reference wave function and therefore achieves greatly reduced computational costs compared to FCI. iFCI through the 3-body expansion is demonstrated on four model transition-metal complexes involving the metals Zn, V, and Cu. Screening techniques to increase the computational efficiency of iFCI are proposed and tested, showing reduction in the number of 3-body terms by more than 90% with controlled errors. The largest complex treated by iFCI has 142 valence electrons, all of which are correlated among the full set of 444 active orbitals. Computed spin gaps approach experimental results for the four complexes, though room for improvement remains.

74 ATOMIC AND MOLECULAR PHYSICS↗