The accuracy limit of chemical shift predictions for species in aqueous solution

Maste, Stefan; Sharma, Bikramjit; Pongratz, Tim; Grabe, Bastian; Hiller, Wolf; Erlach, Markus Beck; Kremer, Werner; Kalbitzer, Hans Robert; Marx, Dominik; Kast, Stefan M.

doi:10.1039/d3cp05471c

“…These first-principles simulations dynamically solve the Schrödinger equation, explicitly incorporating electronic many-body effects and solute–solvent interactions without relying on predefined parameters . Despite their high computational cost, these simulations have been widely adopted to incorporate dynamical effects in predicting NMR properties, including 1 H, 13 C, and 15 N chemical shifts. − Throughout the AIMD simulations, TPB maintains its structural characteristics observed in the crystal phase with the H1 and H3 atoms proximal to the aromatic rings and the H2 and H4 atoms close to the O atoms in the tosylate groups. To characterize the configuration of TPB, we use d HX and d HO as geometric parameters and calculate the free energies as F = prefix− k B T ln P ( d H O , d H X ) P max Here, k B is the Boltzmann constant and T is the simulation temperature.…”

Section: Resultsmentioning

confidence: 99%

Unexpected Intermolecular C–H···O Hydrogen Bonds and ¹H NMR Chemical Shifts in a Key Linker for Fluorine-18 Labeling of Dimeric Drugs

Wang,

Li,

Wang

et al. 2024

J. Phys. Chem. B

0

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The compound 2-{[(trifluoromethyl)sulfonyl]oxy}propane-1,3-diyl bis(4-methylbenzenesulfonate) (TPB) is a crucial intermediate in the synthesis of 18 F-radiolabeled cromolyn derivatives. In this work, we combine 1 H NMR spectroscopy, Xray crystallography, ab initio molecular dynamics, and NMR calculations to examine the structure, interactions, and solvation dynamics of the TPB molecule. In CDCl 3 , the CH 2 groups within its glyceryl-derived linker exhibit a single set of proton signals in the 1 H NMR measurements. However, when TPB is dissolved in DMSO-d 6 , distinct splitting patterns emerge despite its seemingly symmetric chemical structure. Crystallographic analysis further unveils the absence of overall symmetry in its three-dimensional arrangement. To elucidate these unique NMR features, we carry out ab initio molecular dynamics simulations and characterize the solvation structures and dynamics of TPB in CHCl 3 and DMSO solutions. In contrast to the predominantly nonpolar nature of the CHCl 3 solvents, DMSO directly participates in C−H•••O hydrogen-bonding interactions with the solute molecule, leading to the splitting of its −CH 2 chemical shifts into two distinct distributions. The comprehensive understanding of the structure and solvation interactions of TPB provides essential insights into its application in the radiofluorination reactions of cromolyn derivatives and holds promise for the future development of radiolabeled dimeric drugs.

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Solvent‐Controlled Separation of Integratively Self‐Sorted Pd₂L^A₂L^B₂ Coordination Cages

Ebbert,

Sendzik,

Neukirch

et al. 2024

Angewandte Chemie

0

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The integrative implementation of multiple different components into metallosupramolecular self‐assemblies requires sophisticated strategies to avoid the formation of statistical mixtures. Previously, the key focus was set on thermodynamically driven reactions of simple homoleptic into complex heteroleptic structures. Using Pd2LA2LB2‐type coordination cages, we herein show that integrative self‐sorting can be reversed by a change of solvent (from DMSO to MeCN) to favor narcissistic re‐segregation into coexisting homoleptic species Pd2LA4 and Pd3LB6. Full separation (“unsorting”) back to a mixture of the homoleptic precursors was finally achieved by selective precipitation of Pd3LB6with anionic guest G1 from MeCN, keeping pure Pd2LA4 in solution. When a mixture of homoleptic Pd3LB6 and heteroleptic Pd2LA2LB2 is exposed to a combination of two different di‐anions (G1 and G2) in DMSO, selective guest uptake gives rise to two defined coexisting host‐guest complexes. A joint experimental and deep theoretical investigation via liquid‐state integral equation theory of the reaction thermodynamics on a molecular level accompanied by solvent distribution analysis hints at solvent expulsion from Pd2LA4 to favor the formation of Pd2LA2LB2 in DMSO as the key entropic factor for determining the solvent‐specific modulation of the cage conversion equilibrium.

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Solvent‐Controlled Separation of Integratively Self‐Sorted Pd₂L^A₂L^B₂ Coordination Cages

Ebbert,

Sendzik,

Neukirch

et al. 2024

Angew Chem Int Ed

0

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The integrative implementation of multiple different components into metallosupramolecular self‐assemblies requires sophisticated strategies to avoid the formation of statistical mixtures. Previously, the key focus was set on thermodynamically driven reactions of simple homoleptic into complex heteroleptic structures. Using Pd2LA2LB2‐type coordination cages, we herein show that integrative self‐sorting can be reversed by a change of solvent (from DMSO to MeCN) to favor narcissistic re‐segregation into coexisting homoleptic species Pd2LA4 and Pd3LB6. Full separation (“unsorting”) back to a mixture of the homoleptic precursors was finally achieved by selective precipitation of Pd3LB6with anionic guest G1 from MeCN, keeping pure Pd2LA4 in solution. When a mixture of homoleptic Pd3LB6 and heteroleptic Pd2LA2LB2 is exposed to a combination of two different di‐anions (G1 and G2) in DMSO, selective guest uptake gives rise to two defined coexisting host‐guest complexes. A joint experimental and deep theoretical investigation via liquid‐state integral equation theory of the reaction thermodynamics on a molecular level accompanied by solvent distribution analysis hints at solvent expulsion from Pd2LA4 to favor the formation of Pd2LA2LB2 in DMSO as the key entropic factor for determining the solvent‐specific modulation of the cage conversion equilibrium.

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The accuracy limit of chemical shift predictions for species in aqueous solution

Abstract: Accurate predictions of chemical shifts of species in aqueous solution are possible by combining ab initio molecular dynamics simulations for ensembles of locally solvated target and reference compound (DSS) with quantum-mechanical solvation models.

Cited by 4 publications

References 78 publications

Unexpected Intermolecular C–H···O Hydrogen Bonds and ¹H NMR Chemical Shifts in a Key Linker for Fluorine-18 Labeling of Dimeric Drugs

Unexpected Intermolecular C–H···O Hydrogen Bonds and ¹H NMR Chemical Shifts in a Key Linker for Fluorine-18 Labeling of Dimeric Drugs

Solvent‐Controlled Separation of Integratively Self‐Sorted Pd₂L^A₂L^B₂ Coordination Cages

Solvent‐Controlled Separation of Integratively Self‐Sorted Pd₂L^A₂L^B₂ Coordination Cages

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The accuracy limit of chemical shift predictions for species in aqueous solution

Abstract: Accurate predictions of chemical shifts of species in aqueous solution are possible by combining ab initio molecular dynamics simulations for ensembles of locally solvated target and reference compound (DSS) with quantum-mechanical solvation models.

Cited by 4 publications

References 78 publications

Unexpected Intermolecular C–H···O Hydrogen Bonds and 1H NMR Chemical Shifts in a Key Linker for Fluorine-18 Labeling of Dimeric Drugs

Unexpected Intermolecular C–H···O Hydrogen Bonds and 1H NMR Chemical Shifts in a Key Linker for Fluorine-18 Labeling of Dimeric Drugs

Solvent‐Controlled Separation of Integratively Self‐Sorted Pd2LA2LB2 Coordination Cages

Solvent‐Controlled Separation of Integratively Self‐Sorted Pd2LA2LB2 Coordination Cages

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Product

Resources

About

Unexpected Intermolecular C–H···O Hydrogen Bonds and ¹H NMR Chemical Shifts in a Key Linker for Fluorine-18 Labeling of Dimeric Drugs

Unexpected Intermolecular C–H···O Hydrogen Bonds and ¹H NMR Chemical Shifts in a Key Linker for Fluorine-18 Labeling of Dimeric Drugs

Solvent‐Controlled Separation of Integratively Self‐Sorted Pd₂L^A₂L^B₂ Coordination Cages

Solvent‐Controlled Separation of Integratively Self‐Sorted Pd₂L^A₂L^B₂ Coordination Cages