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66 Publications visible to you, out of a total of 66
Entropy-Driven Chain Effects on Ligation Chemistry

Abstract (Expand)

We report the investigation of fundamental entropic chain effects that enable the tuning of modular ligation chemistry – for example dynamic Diels–Alder (DA) reactions in materials applications – not … only classically via the chemistry of the applied reaction sites, but also via the physical and steric properties of the molecules that are being joined. Having a substantial impact on the reaction equilibrium of the reversible ligation chemistry, these effects are important when transferring reactions from small molecule studies to larger or other entropically very dissimilar systems. The effects on the DA equilibrium and thus the temperature dependent degree of debonding (%debond) of different cyclopentadienyl (di-)functional poly(meth-)acrylate backbones (poly(methyl methacrylate), poly(iso-butyl methacrylate), poly(tert-butyl methacrylate), poly(iso-butyl acrylate), poly(n-butyl acrylate), poly(tert-butyl acrylate), poly(methyl acrylate) and poly(isobornyl acrylate)), linked via a difunctional cyanodithioester (CDTE) were examined via high temperature (HT) NMR spectroscopy as well as temperature dependent (TD) SEC measurements. A significant impact of not only chain mass and length with a difference in the degree of debonding of up to 30% for different lengths of macromonomers of the same polymer type but – remarkably – as well the chain stiffness with a difference in bonding degrees of nearly 20% for isomeric poly(butyl acrylates) is found. The results were predicted, reproduced and interpreted via quantum chemical calculations, leading to a better understanding of the underlying entropic principles.

Authors: Kai Pahnke, Josef Brandt, Ganna Gryn'ova, Peter Lindner, Ralf Schweins, Friedrich Georg Schmidt, Albena Lederer, Michelle L. Coote, Christopher Barner-Kowollik

Date Published: 2015

Publication Type: Journal

Mechanisms and Energetics of Potassium Channel Block by Local Anesthetics and Antifungal Agents

Abstract (Expand)

Many drug molecules inhibit the conduction of several families of cation channels by binding to a small cavity just below the selectivity filter of the channel protein. The exact mechanisms governing … drug–channel binding and the subsequent inhibition of conduction are not well understood. Here the inhibition of two K+ channel isoforms, Kv1.2 and KCa3.1, by two drug molecules, lidocaine and TRAM-34, is examined in atomic detail using molecular dynamics simulations. A conserved valine-alanine-valine motif in the inner cavity is found to be crucial for drug binding in both channels, consistent with previous studies of similar systems. Potential of mean force calculations show that lidocaine in its charged form creates an energy barrier of ∼6 kT for a permeating K+ ion when the ion is crossing over the drug, while the neutral form of lidocaine has no significant effect on the energetics of ion permeation. On the other hand, TRAM-34 in the neutral form is able to create a large energy barrier of ∼10 kT by causing the permeating ion to dehydrate. Our results suggest that TRAM-34 analogues that remain neutral and permeable to membranes under acidic conditions common to inflammation may act as possible drug scaffolds for combating local anesthetic failure in inflammation.

Authors: Rong Chen, Ganna Gryn’ova, Yingliang Wu, Michelle L. Coote, Shin-Ho Chung

Date Published: 24th Oct 2014

Publication Type: Journal

Desorption Electrospray Ionisation Mass Spectrometry of Stabilised Polyesters Reveals Activation of Hindered Amine Light Stabilisers

Abstract (Expand)

The use of hindered amine light stabilizers (HALS) to retard thermo- and photo-degradation of polymers has become increasingly common. Proposed mechanisms of polymer stabilisation involve significant … changes to the HALS chemical structure; however, reports of the characterisation of these modified chemical species are limited. To better understand the fate of HALS and determine their in situ modifications, desorption electrospray ionisation mass spectrometry (DESI-MS) was employed to characterise ten commercially available HALS present in polyester-based coil coatings. TINUVIN® 770, 292, 144, 123, 152, and NOR371; HOSTAVIN® 3052, 3055, 3050, and 3058 were separately formulated with a pigmented, thermosetting polyester resin, cured on metal at 262 °C and analysed directly by DESI-MS. High-level ab initio molecular orbital theory calculations were also undertaken to aid the mechanistic interpretation of the results. For HALS containing N-substituted piperidines (i.e., N–CH3, N–C(O)CH3, and N–OR) a secondary piperidine (N–H) analogue was detected in all cases. The formation of these intermediates can be explained either through hydrogen abstraction based mechanisms or direct N–OR homolysis with the former dominant under normal service temperatures (ca. 25–80 °C), and the latter potentially becoming competitive under the high temperatures associated with curing (ca. 230–260 °C).

Authors: Martin R.L. Paine, Ganna Gryn'ova, Michelle L. Coote, Philip J. Barker, Stephen J. Blanksby

Date Published: 2014

Publication Type: Journal

Radical orbital switching

Abstract

Not specified

Authors: G. Gryn’ova, M. L. Coote

Date Published: 2014

Publication Type: Misc

Origin and Scope of Long-Range Stabilizing Interactions and Associated SOMO–HOMO Conversion in Distonic Radical Anions

Abstract (Expand)

High-level quantum-chemical methods have been used to study the scope and physical origin of the significant long-range stabilizing interactions between nonmutually conjugated anion and radical moieties … in SOMO–HOMO converted distonic radical anions. In such species, deprotonation of the acid fragment can stabilize the remote radical by tens of kilojoules, or, analogously, formation of a stable radical (by abstraction or homolytic cleavage reactions) increases the acidity of a remote acid by several pKa units. This stabilization can be broadly classified as a new type of polar effect that originates in Coloumbic interactions but, in contrast to standard polar effects, persists in radicals with no charge-separated (i.e., dipole) resonance contributors, is nondirectional, and hence of extremely broad scope. The stabilization upon deprotonation is largest when a highly delocalized radical is combined with an initially less stable anion (i.e., the conjugate base of a weaker acid), and is negligible for highly localized radicals and/or stable anions. The effect is largest in the gas phase and low-polarity solvents but is quenched in water, where the anion is sufficiently stabilized. These simple rules can be employed to design various switchable compounds able to reversibly release radicals in response to pH for use in, for example, organic synthesis or nitroxide-mediated polymerization. Moreover, given its wide chemical scope, this effect is likely to influence the protonation state of many biological substrates under radical attack and may contribute to enzyme catalysis.

Authors: Ganna Gryn’ova, Michelle L. Coote

Date Published: 3rd Oct 2013

Publication Type: Journal

Switching Radical Stability by pH-Induced Orbital Conversion

Abstract (Expand)

In most radicals the singly occupied molecular orbital (SOMO) is the highest-energy occupied molecular orbital (HOMO); however, in a small number of reported compounds this is not the case. In the … present work we expand significantly the scope of this phenomenon, known as SOMO–HOMO energy-level conversion, by showing that it occurs in virtually any distonic radical anion that contains a sufficiently stabilized radical (aminoxyl, peroxyl, aminyl) non-π-conjugated with a negative charge (carboxylate, phosphate, sulfate). Moreover, regular orbital order is restored on protonation of the anionic fragment, and hence the orbital configuration can be switched by pH. Most importantly, our theoretical and experimental results reveal a dramatically higher radical stability and proton acidity of such distonic radical anions. Changing radical stability by 3–4 orders of magnitude using pH-induced orbital conversion opens a variety of attractive industrial applications, including pH-switchable nitroxide-mediated polymerization, and it might be exploited in nature.

Authors: Ganna Gryn'ova, David L. Marshall, Stephen J. Blanksby, Michelle L. Coote

Date Published: 1st Jun 2013

Publication Type: Journal

Which Side-Reactions Compromise Nitroxide Mediated Polymerization?

Abstract (Expand)

The mechanism of the nitroxide mediated polymerization (NMP) is well understood, however less is known about the side-reactions that interfere and in certain cases severely compromise it. Experimental … studies inevitably involve model fitting leading to at times contradictory conclusions as to which elementary side-reactions are behind the failure of a given NMP system. In the present work we use high-level quantum-chemical calculations to obtain the rate coefficients of the various side-reactions, both suggested previously and considered here for the first time, and first principles PREDICI kinetic simulations to identify the most deleterious side-reactions involved in the TEMPO, SG1 and DPAIO mediated polymerization of styrene, acrylate and methacrylate monomers. We show that the core mechanism for the thermal decomposition of alkoxyamines differs between the uni- and polymeric species, which often makes such experiments not suitable for modelling the NMP conditions. We also find that the main side-reaction responsible for the failure of TEMPO and SG1 in methacrylate homopolymerization is an intramolecular alkoxyamine decomposition (often referred to as ‘disproportionation’) via a Cope-type elimination, however in the case of SG1 the polymerization outcome is additionally affected by the equilibrium constant of alkoxyamine bond homolysis. On the basis of these findings, complemented by a thorough analysis of available experimental data, we define guidelines for minimising occurrence of the side-reactions and thus improving NMP. Finally, the accurate first principles rate parameters reported in this study should prove useful for subsequent kinetic modelling oriented at optimising different polymerization conditions.

Authors: Ganna Gryn'ova, Ching Yeh Lin, Michelle L. Coote

Date Published: 2013

Publication Type: Journal

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