Barbara Hachuła

Solid-state polypeptides undergo continuous conformational reorganization when subjected to various environmental stimuli, reshaping their macroscopic physical behavior. Here, we investigate this phenomenon specifically under thermal treatment using α-poly-l-lysine hydrobromide (α-PLL), an ionic polypeptide containing Br– counterions, as a model system. By combining thermogravimetric analysis (TGA), Fourier-transform infrared (FT-IR) spectroscopy, wide-angle X-ray scattering (WAXS), differential scanning calorimetry (DSC), and broadband dielectric spectroscopy (BDS), we show that freeze-dried α-PLL initially contains mixed α-helical, β-sheet, and β-turn/antiparallel β-sheet conformations. After removal of loosely bound water, thermal treatment drives a transformation toward β-sheet-rich structures. This process is cooperative and thermally activated, with an apparent activation energy of approximately 64 kJ mol–1, indicating that β-sheet formation requires collective rearrangement of hydrogen-bonded polypeptide chains. The structural transformation is not limited to local changes in secondary structure. WAXS reveals that α-PLL exhibits liquid-crystalline-like two-dimensional hexagonal packing, which is reorganized in a molecular-weight-dependent manner as β-sheet-rich architectures develop with increasing temperature. Most importantly, this conformational reorganization produces two unexpected changes in the physical response of α-PLL. First, the formation of β-sheet-rich structures is accompanied by a decrease in glass transition temperature (Tg), showing that secondary-structure ordering does not necessarily rigidify the polypeptide matrix. Second, the frequency-dependent conductivity, σ′(f), systematically decreases over a broad frequency range upon annealing, although the β-sheet-rich state exhibits stronger hydrogen bonds. This suggests that charge transport in α-PLL is promoted not by the stronger, more static interchain hydrogen-bonding network of β-sheets, but by the α-helical state, which may provide a more favorable electrostatic environment for Br– migration. These findings reveal a direct link between secondary-structure transformation, glass-transition dynamics, mesoscale packing, and ion transport, establishing α-PLL as a model solid-state polypeptide electrolyte in which conformational reorganization governs both molecular mobility and electrical response.

Hydrogen bonds dictate molecular conformation and are essential in pharmaceutical design, supramolecular chemistry, and catalysis, among others. The ability to manipulate a molecule's potential for forming molecular hydrogen bonds has attracted significant interest, as it can affect bioactivity and physicochemical properties. To clarify the dynamics of certain profen derivatives that influence the structure, activity, and interactions with biological targets, as well as to gain insights into their conformational dynamics within biological systems, the IR spectra of RS-ibuprofen and RS-ketoprofen were recorded at 293 K within the υ_S(O-H) band frequency range and analyzed theoretically from a quantum analysis perspective. The primary distinctions among the spectra of these two different systems lie in the corresponding bandshapes and the intricate structure that defines the bands. An integrated quantum model susceptible to clarifying the differences in the IR spectral density of RS-ibuprofen and RS-ketoprofen is proposed and can be extended to address other complex hydrogen-bonded systems. A satisfactory agreement is achieved between the simulated spectra and experimental results by utilizing a set of physical input parameters that are validated by theoretical and experimental grounds. The quantum approach emphasizes the significance of dynamic cooperative interactions among the vibrational modes, specifically the "Davydov coupling" and "strong anharmonic coupling" mechanisms, in conjunction with the damping mechanisms in the formation of the spectral characteristics of RS-ibuprofen and RS-ketoprofen. This suggests that the synergistic effects of these mechanisms, within the framework of linear response theory, can be regarded as the primary dependable cause of the unconventional IR spectral properties observed. It is anticipated that this innovative algorithm will minimize the discrepancies between the experimental and simulated spectra and may facilitate the computation of spectra in more intricate hydrogen-bonded systems.

This paper investigates the effect of high pressure on the dynamics, intermolecular interactions, and association mechanisms of 3-phenylpropanal (3P1 Pal). Dielectric investigations have revealed an unusual behavior of the Debye process at high compression, indicating a distinct clustering mechanism. Complementary Fourier Transform Infrared and Raman spectroscopy studies, supported by molecular dynamics simulations, have shown that, at high pressure, molecular clustering is dominated by π-stacking and strong, distorted hydrogen bonds, with larger and more compact aggregates, compared to those formed at low temperatures. Overall, high compression effectively tunes both dynamics and association patterns in 3P1 Pal, revealing key aspects of self-assembly in viscous molecular liquids.

In this paper, we investigated the thermal, dynamical, and structural properties, as well as association patterns, in 3-phenyl-1-propanol (3P1Pol) and 3-phenyl-1-propanal (3P1Pal), with special attention paid to the latter compound. Both systems turned out to be good glass formers, differing by 17 K in the glass transition temperature, which indicated a strong change in the self-assembly pattern. This supposition was further confirmed by the analysis of dielectric spectra, where, apart from the α-relaxation, also a unique Debye (D)-mode, being a fingerprint of the self-association, characterized by different dynamical properties (dielectric strength, timescale separation from the α-process), was detected in both samples. Further diffraction and infrared investigations, supported by density functional theory computations and molecular dynamics (MD) simulations, revealed that hydrogen (H)-bonds play a key role in the association in 3P1Pol, while in 3P1Pal, there are at least five different intermolecular interactions involving dipole–dipole forces and π-stacking, as well as extraordinary H-bonds formed between methylene groups neighboring with the formyl unit and carbonyl moiety. Finally, optimized dimeric structures, along with MD simulations, allowed us to propose a molecular mechanism responsible for the D-process in 3P1Pal. The presented data systematize previous understanding of molecular association as well as open new ways of exploring this phenomenon in aldehydes.

In this paper, X-ray diffraction (XRD), differential scanning calorimetry (DSC), broadband dielectric (BDS), and Fourier transform infrared (FTIR) spectroscopy supported by molecular dynamics (MD) simulations and quantum chemical computations were applied to investigate the structural and thermal properties, molecular dynamics, and H-bonding pattern of R-, S-, and RS-flurbiprofen (FLP). Experimental data indicated various spatial molecular arrangements in crystalline forms of examined systems, which seemed to disappear in the liquid state. Surprisingly, deeper analysis of high-pressure dielectric data revealed unexpected variation in the activation volume of pure enantiomers and a racemate. MD simulations showed that it is an effect of the clusterization phenomenon and a higher population of small associates in the former samples. Moreover, theoretical consideration exposed the particular role of unspecific F-Π interactions as a driving force underlying local molecular arrangements of molecules in the liquid and the crystal lattice of R-, S-, and RS-FLP.