Noncoulomb variation of ion pairing in polar solvents

We have discovered and studied a telesubstitution reaction in a biologically important heterocyclic ring system. Conditions that favour the tele-substitution pathway were identified: the use of increased equivalents of the nucleophile or decreased equivalents of base, or the use of softer nucleophiles, less polar solvents and larger halogens on the electrophile. Using results from X-ray crystallography and isotope labelling experiments a mechanism for this unusual transformation is proposed. We focused on this triazolopyrazine as it is the core structure of the in vivo active anti-plasmodium compounds of Series 4 of the Open Source Malaria consortium. Archive of the electronic laboratory notebook with the description of all conducted experiments and raw NMR data could be accessed via following link <a href="https://ses.library.usyd.edu.au/handle/2123/21890">https://ses.library.usyd.edu.au/handle/2123/21890</a> . For navigation between entries of laboratory notebook please use file "Strings for compounds in the article.pdf" that works as a reference between article codes and notebook codes, also this file contain SMILES for these compounds.

Download Full-text

Ion Pairing and Dielectric Decrement in Glycosaminoglycan Brushes

10.26434/chemrxiv.13501698.v1 ◽

2020 ◽

Author(s):

James Sterling ◽

Wenjuan Jiang ◽

Wesley M. Botello-Smith ◽

Yun L. Luo

Keyword(s):

Molecular Dynamics ◽

Ion Pairs ◽

Mean Field ◽

Salt Bridge ◽

Ion Pairing ◽

Donnan Potential ◽

Mean Field Models ◽

Ion Exclusion ◽

Dynamics Simulations ◽

Contact Ion Pairs

Molecular dynamics simulations of hyaluronic acid and heparin brushes are presented that show important effects of ion-pairing, water dielectric decrease, and co-ion exclusion. Results show equilibria with electroneutrality attained through screening and pairing of brush anionic charges by cations. Most surprising is the reversal of the Donnan potential that would be expected based on electrostatic Boltzmann partitioning alone. Water dielectric decrement within the brush domain is also associated with Born hydration-driven cation exclusion from the brush. We observe that the primary partition energy attracting cations to attain brush electroneutrality is the ion-pairing or salt-bridge energy associated with cation-sulfate and cation-carboxylate solvent-separated and contact ion pairs. Potassium and sodium pairing to glycosaminoglycan carboxylates and sulfates consistently show similar abundance of contact-pairing and solvent-separated pairing. In these crowded macromolecular brushes, ion-pairing, Born-hydration, and electrostatic potential energies all contribute to attain electroneutrality and should therefore contribute in mean-field models to accurately represent brush electrostatics.

Download Full-text

Stereospecific 1,3-H Transfer of Indenols Proceeds via Persistent Ion-Pairs Anchored By NH···Pi Interactions

10.26434/chemrxiv.7057892.v1 ◽

2018 ◽

Author(s):

David Ascough ◽

Fernanda Duarte ◽

Robert Paton

Keyword(s):

Computational Analysis ◽

Ion Pairs ◽

Ion Pair ◽

Hydrogen Atom Transfer ◽

Polar Solvents ◽

Chirality Transfer ◽

Activation Barriers ◽

Sense And Avoid ◽

Phase Dynamics ◽

Pi Interactions

The base-catalyzed rearrangement of arylindenols is a rare example of a suprafacial [1,3]-hydrogen atom transfer. The mechanism has been proposed to proceed via sequential [1,5]-sigmatropic shifts, which occur in a selective sense and avoid an achiral intermediate. A computational analysis using quantum chemistry casts serious doubt on these suggestions: these pathways have enormous activation barriers and in constrast to what is observed experimentally, they overwhelmingly favor a racemic product. Instead we propose that a suprafacial [1,3]-prototopic shift occurs in a two-step deprotonation/reprotonation sequence. This mechanism is favored by 15 kcal mol-1 over that previously proposed. Most importantly, this is also consistent with stereospecificity since reprotonation occurs rapidly on the same p-face. We have used explicitly-solvated molecular dynamics studies to study the persistence and condensed-phase dynamics of the intermediate ion-pair formed in this reaction. Chirality transfer is the result of a particularly resilient contact ion-pair, held together by electrostatic attraction and a critical NH···p interaction which ensures that this species has an appreciable lifetime even in polar solvents such as DMSO and MeOH.

Download Full-text