A Family of Bisnaphthyl C2-Symmetric and Asymmetric Clefts: Synthesis, Solid-State Structure, and Calculation of the Interplanar Angle.

The synthesis of a new family of naphthalenoid C2-symmetric clefts has been realized through a four-step synthetic sequence giving three C2-symmetric clefts and a rare nonsymmetric example. Subsequently, stereoselective reduction of the carbonyl groups at C-8 and C-16 then provides cleft molecules with hydrogen bonding potential. Using single-crystal X-ray and computational analysis, the cleft angle of the dione has been determined.

The role of osmolytes in the temperature-triggered conformational transition of poly(N-vinylcaprolactam): an experimental and computational study.

Biomedical industries are widely exploring the use of thermo-responsive polymers (TRPs) in the advanced development of drug delivery and in many other pharmaceutical applications. There is a great need to investigate the use of less toxic and more (bio-)compatible TRPs employing several additives, which could modify the conformational transition behavior of TRPs in aqueous solution. To move forward in this aspect, we have chosen the less toxic bio-based polymer poly(N-vinylcaprolactam) (PVCL) and three different methylamine-based osmolytes, trimethylamine N-oxide (TMAO), betaine and sarcosine, in order to investigate their particular interactions with the polymer segments in PVCL and therefore the corresponding changes in the thermo-responsive conformational behavior. Several biophysical techniques, UV-visible spectroscopy, fluorescence spectroscopy, dynamic light scattering (DLS) and laser Raman spectroscopy, as well as classical computer simulation methods such as molecular dynamics are employed in the current work. All the studied methylamines are found to favor the hydrophobic collapse of the polymer thus stabilizing the globular state of PVCL. Sarcosine is observed to cause the maximum decrease in lower critical solution temperature (LCST) of PVCL followed by TMAO and then betaine. The differences observed in the LCST values of PVCL in the presence of these molecules can be attributed to the different polymer-osmolyte interactions. The less sterically hindered N atom in the case of sarcosine causes a significant difference in the phase transition temperature values of PVCL compared to betaine and TMAO, where the nitrogen atom is buried by three methyl groups attached to it.

Molecular dynamics study of the LCST transition in aqueous poly(N-n-propylacrylamide).

The breadth of technological applications of smart polymers relies on the possibility of tuning their molecular structure to respond to external stimuli. In this context, N-substituted acrylamide-based polymers are widely studied thermoresponsive polymers. Poly(N-n-propylacrylamide) (PNnPAm), which is a structural isomer of the poly(N-isopropylacrylamide) (PNIPAm) exhibits however, a lower phase transition in aqueous solution. In this work, we use all-atom molecular dynamics simulations of PNnPAm in aqueous solutions to study, from a microscopic point-of-view, the influence of chain size and concentration on the LCST of PNnPAm. Our analysis shows that the collapse of a single oligomer of PNnPAm upon heating is dependent on the chain length and corresponds to a complex interplay between hydration and intermolecular interactions. Analysis of systems with multiple chains shows an aggregation of PNnPAm chains above the LCST.

Reply to the 'Comment on "Relating side chain organization of PNIPAm with its conformation in aqueous methanol"' by A. Pica and G. Graziano, Soft Matter, 2017, 13, DOI: 10.1039/C7SM01065F.

We have recently proposed preferential binding by a cosolvent as the mechanism for chain collapse under co-non-solvency. Here we summarise our earlier works and provide further evidence that alcohol preferentially binds to PNIPAm, forming cosolvent bridges, and thus drives the transition. We also clarify some of the common misconceptions evoked in this debate with Pica and Graziano (PG), reinforcing the arguments of our earlier reply-comment [Soft Matter, 2017, 13, 2292] and published works.

Reply to the 'Comment on "Relating side chain organization of PNIPAm with its conformation in aqueous methanol"' by N. van der Vegt and F. Rodriguez-Ropero, Soft Matter, 2017, 13, DOI: 10.1039/C6SM02139E.

In a comment van der Vegt and Rodriguez-Ropero (vdVRR) challenged our explanation of the co-non-solvency effect of PNIPAm in aqueous methanol solutions. They argue, based on a careful selection of published studies including some of their own, that direct repulsions between the different constituents are sufficient to understand this phenomenon. According to vdVRR, the emerging view of entropic collapse, put forward by Flory (1910-1985) to explain common polymers in poor solvents, would be enough to explain co-non-solvency. In this reply we attempt to bring this discussion into firmer grounds. We provide a more comprehensive view of available experimental, numerical and theoretical results and review basic concepts of physical chemistry and of statistical mechanics of polymer collapse that show how methanol mediated attractions between chain monomers are required to understand this fascinating behavior.

Effects of stereochemistry and copolymerization on the LCST of PNIPAm.

Poly(N-isopropylacrylamide) (PNIPAm) is a smart polymer that presents a lower critical transition temperature (LCST) of 305 K. Interestingly, this transition point falls within the range of the human body temperature, making PNIPAm a highly suitable candidate for bio-medical applications. However, it is sometimes desirable to have a rather flexible tuning of the LCST of these polymers to further increase their range of applications. In this work, we use all-atom molecular dynamics simulations to study the LCST of PNIPAm-based (co-)polymers. We study different molecular architectures where the polymer sequences are tuned either by modifying its stereochemistry or by the co-polymerization of PNIPAm with acrylamide (Am) units. Our analysis connects global polymer conformations with the microscopic intermolecular interactions. These findings suggest that the collapse of a PNIPAm chain upon heating is dependent on the hydration structure around the monomers, which is strongly dependent on the tacticity and the presence of more hydrophilic acrylamide monomers. Our results are found to be in good agreement with the existing experimental data.

Relating side chain organization of PNIPAm with its conformation in aqueous methanol.

Combining nuclear magnetic resonance (NMR), dynamic light scattering (DLS), and µs long all-atom simulations with two million particles, we establish a delicate correlation between increased side chain organization of PNIPAm and its collapse in aqueous methanol mixtures. We find that the preferential binding of methanol with PNIPAm side chains, bridging distal monomers along the polymer backbone, results in increased organization. Furthermore, methanol-PNIPAm preferential binding is dominated by hydrogen bonding. Our findings reveal that the collapse of PNIPAm is dominated by enthalpic interactions and that the standard poor solvent (entropic) effects play no major role.

C-IBI: Targeting cumulative coordination within an iterative protocol to derive coarse-grained models of (multi-component) complex fluids.

We present a coarse-graining strategy that we test for aqueous mixtures. The method uses pair-wise cumulative coordination as a target function within an iterative Boltzmann inversion (IBI) like protocol. We name this method coordination iterative Boltzmann inversion (C-IBI). While the underlying coarse-grained model is still structure based and, thus, preserves pair-wise solution structure, our method also reproduces solvation thermodynamics of binary and/or ternary mixtures. Additionally, we observe much faster convergence within C-IBI compared to IBI. To validate the robustness, we apply C-IBI to study test cases of solvation thermodynamics of aqueous urea and a triglycine solvation in aqueous urea.

Why does high pressure destroy co-non-solvency of PNIPAm in aqueous methanol?

It is well known that poly(N-isopropylacrylamide) (PNIPAm) exhibits an interesting, yet puzzling, phenomenon of co-non-solvency. Co-non-solvency occurs when two competing good solvents for PNIPAm, such as water and alcohol, are mixed together. As a result, the same PNIPAm collapses within intermediate mixing ratios. This complex conformational transition is driven by preferential binding of methanol with PNIPAm. Interestingly, co-non-solvency can be destroyed when applying high hydrostatic pressures. In this work, using a large scale molecular dynamics simulation employing high pressures, we propose a microscopic picture behind the suppression of the co-non-solvency phenomenon. Based on thermodynamic and structural analysis, our results suggest that the preferential binding of methanol with PNIPAm gets partially lost at high pressures, making the background fluid reasonably homogeneous for the polymer. This is consistent with the hypothesis that the co-non-solvency phenomenon is driven by preferential binding and is not based on depletion effects.