Category: group meetings

Valeria’s comment on: Reversible Regulation of Thermoresponsive Property of Dithiomaleimide-Containing Copolymers via Sequential Thiol Exchange Reactions

By Valeria Burgos Caldero

VABC blog image 18-05.jpg

The main purpose of this article was to synthesize multi-responsive polymers that could be reversibly modified to adjust their LCST. Indeed, these researchers were able to develop a system in which multiple thiol exchanges were made, and in turn, they could determine how the thiols affected the transition temperature of the polymer. They used a copolymer containing P(TEGA) and DMMA. By performing transmission measurements at various temperatures, they concluded that as the thiol changed, the transition temperature of polymer varied depending on the resulting hydrophobicity. More polar functionalities increased the transition temperature and less polar ones decreased it. They were able to demonstrate the reversibility of the modifications since they managed to return to their original functionality after various thiol exchanges. Finally, they implemented a fluorescence signal to monitor the reaction progress. They found that thioglucose quenches the polymer’s fluorescence while making the compound soluble throughout the range of temperatures. With these findings, a wide range of possibilities were opened, since now, if you want a polymer for a specific type of function where a specific temperature response is needed, it is easily accessible by adding the corresponding thiol to the polymer solution. The mechanism of turning off the fluorescence may give access to reversible systems in aqueous conditions.
In general, I found it much simpler to prepare for this article than for the first one I presented. I feel that by doing these exercises of presenting scientific articles I have been acquiring maturity in the analysis process since it was difficult for me to understand articles in the beginning. Something that I found missing in the article is that they never explained the experimental procedure on how they achieved reversibility after adding different thiols to the same sample. I liked that they used common thiols, some of which we use in our research and others that maybe we could apply. In general, the article relates a lot to the research I’m doing with Diana. It could be useful to try to see the stimuli-responsive variations in the compounds that we are synthesizing. Maybe because it is related to variations in functionalities with thiols, similar to my own research, I found it more enjoyable to prepare the discussion and understand the material in the article.

Tang, 2016. Reversible Regulation of Thermoresponsive Property of Dithiomaleimide-Containing Copolymers via Sequential Thiol Exchange Reactions

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Luxene’s comment on: Selective Tuning of Elastin-like Polypeptide Properties via Methionine Oxidation

By Luxene Belfleur

Luxene blog image 18-05

Figure 1. Kekule structure of and synthesis of ELP 2 and 3. Cartoon representation of ELPs solution, the LCST behavior and measurement of ELPs

In this article, the authors reported the LCST modulation of Elastin-like polymers (ELP) by the modification towards oxidation reactions of the methionine thioester group of the ELP 1 to form sulfoxide and sulfone ELPs derivatives 2 and 3 respectively (Figure 1). They isolated ELP 1 from plasmid DNA of E.coli bacteria and purified it by SDS-Page. In acidic media, using 30% hydrogen peroxide and 1% of acetic acid or formic acid in water, they obtained ELP derivatives 2 and 3 respectively and the molecular weight and structural elucidation of ELP 1 and its derivatives 2 and 3 had been examined and confirmed by mass spectrometry and NMR respectively.
They performed turbidity experiments to determine the cloud points of those three ELPs. As expected, both ELP derivatives 2 and 3 had a higher LCST behavior (55 °C and 43 °C for 2 and 3 respectively) compared to ELP 1 which is 25 °C (Figure 1). This is due to the increasing of water solubility of the modified ELPs (2 and 3), which required more energy to break the interaction between water and them (ELP 2 and 3) in order to evacuate the hydration shell around these ELPs and favored the collapse of the letters. Moreover, it was expected that ELP 3 would have a higher cloud point than the ELP 2 counterpart, however, this was not the case because the large dipole moment of ELP 3 favored intramolecular and intermolecular interactions between them and the protein respectively which promoted a decrease of the water solubility. They evaluated the influence of the I¯ and NO3¯ anions on the phase transition of the three ELPs and found that those anions had no significant effect on the LCST point of the ELP 1 while I¯ increased the LCST of ELP 2 and NO3¯ decreased the solubility of ELP 3 in agreement with the Hofmeister series effect.
They reported an interesting and straightforward work by turning the LCST behavior of ELPs towards synthetic modification. This work has inspired and motivated my team for designing and synthesizing sulfoxides and sulfones containing guanosine derivatives in order to both, stabilize the thioester containing guanosine derivatives compounds that we synthesize, and modulate the LCST properties of the SGQs that will be made from oxidizing 8ArG derivatives product.

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Luis’ comment on: Guanidinium can both Cause and Prevent the Hydrophobic Collapse of Biomacromolecules

By Luis A. Prieto

LAPC-Blog-GM1805

Heyda, Jungwirth and Cremer collaborated in a study of guanidinium (Gnd+) salts and their effect in lower critical solution temperature (LCST). They studied molecular details of the cause of these transitions by IR-ATR and molecular dynamics simulation where they wanted to understand how Gnd+ salts interacted with the backbone of the Elastin-like peptides (ELP). In previous studies ELPs showed a change in LCST that followed the Hofmeister series in sodium salts but using Gnd+ salts proved to be different, especially Guanidinium thiocyanate (GndSCN) that at low concentrations the LCST decreases, but at high concentrations the LCST increases. They studied particular phenomenon using ATR-IR where they found GndSCN binds strongly with ELPs and resulted in an interesting behavior when the concentration of salt is increased. At low concentrations the polymer collapsed (salting-out) because of cross-linking of the peptide and at high concentrations resolubilization occurred (salting-in). Other salts followed typical behavior of salting-in (guanidinium chloride, weak binding) or salting-out (guanidinium sulfate, poor binding). Coarse-grain and all atom simulations corroborated this finding where they found particular detail of the interaction of the carbonyl groups of the peptide backbone with Gnd+, most likely through H-bonds.

The thermodynamics of this paper I found particularly interesting since it reminded me of everything that I have to re-learn.  An attractive experiment was that they used a melting point apparatus to measure the LCST, meaning the use of small amount of sample to gather fundamental information of the system which is also the case with ATR-IR. An elegant work and also inspirational since our lab works with responsive systems and we will definitively see if we can do the LCST measurement with a melting point instrument. I got to say that I particularly like the all atom simulations and Figure 5, where we can see in molecular detail the interactions of the salts with the peptide where thiocyanate and Gnd+ interact strongly with the hydrophobic parts (V, G) and hydrophilic part (peptide bond), respectively.

LAPC: Heyda, 2017. Guanidinium can both Cause and Prevent the Hydrophobic Collapse of Biomacromolecules

 

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