Structure of Aqueous Solutions of Trimethylaminoxide, Urea, and Their Mixture

Kadtsyn, E. D.; Аникеенко, А. В.; Medvedev, N. N.

doi:10.1134/s0022476618020130

Cited by 7 publications

(2 citation statements)

References 35 publications

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“…This is known as an ‘indirect’ biomolecule stabilisation mechanism as it acts upon the biomolecule through the surrounding water. Studies have explored how TMAO perturbs water structure and dynamics under ambient conditions 41 – 44 , under pressure 36 , 45 – 50 and in the presence of other solutes such as urea 37 , 51 – 55 and Mg(ClO 4 ) 2 56 , 57 . Combinations of MD and spectroscopy (infrared, Fourier transform infrared spectroscopy, terahertz spectroscopy, X-ray absorption) have demonstrated that TMAO forms strong hydrogen bonds with surrounding water molecules due to the large dipole moment on its NO group 34 , 38 , 43 , 53 , 55 , 58 .…”

Section: Introductionmentioning

confidence: 99%

The ability of trimethylamine N-oxide to resist pressure induced perturbations to water structure

et al. 2022

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Trimethylamine N-oxide (TMAO) protects organisms from the damaging effects of high pressure. At the molecular level both TMAO and pressure perturb water structure but it is not understood how they act in combination. Here, we use neutron scattering coupled with computational modelling to provide atomistic insight into the structure of water under pressure at 4 kbar in the presence and absence of TMAO. The data reveal that TMAO resists pressure-induced perturbation to water structure, particularly in retaining a clear second solvation shell, enhanced hydrogen bonding between water molecules and strong TMAO – water hydrogen bonds. We calculate an ‘osmolyte protection’ ratio at which pressure and TMAO-induced energy changes effectively cancel out. Remarkably this ratio translates across scales to the organism level, matching the observed concentration dependence of TMAO in the muscle tissue of organisms as a function of depth. Osmolyte protection may therefore offer a molecular mechanism for the macroscale survival of life in extreme environments.

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Section: Introductionmentioning

confidence: 99%

The ability of trimethylamine N-oxide to resist pressure induced perturbations to water structure

et al. 2022

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“…Most studies indicate that the two solutes act independently by preferential exclusion (TMAO through strengthening water structure and hard-sphere properties) and preferential binding (urea binding to peptide backbones with little effect on water structure) [82]. Thus the counteraction is often attributed to simple additivity of opposing effects without TMAOurea interactions being important [83][84]. Notably, in Fig.…”

Section: Tmao-urea Counteractionmentioning

confidence: 99%

Trimethylamine N-Oxide (TMAO): a Unique Counteracting Osmolyte?

Yancey

2023

PPExMed

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Cells of many organisms facing osmotic shrinkage or swelling undergo homeostatic volume regulation using osmolytes—inorganic ions (Na+, K+, Cl-) in transient disturbances, but special organic osmolytes in long-term disturbances. Neutral amino acids, methylamines and polyols are key examples. Widely termed 'compatible' cosolutes/cosolvents, they—unlike inorganic ions—do not perturb membrane potential nor (supposedly) macromolecules. Indeed, most enhance protein stability in part through preferential exclusion; i.e., they 'dissolve' poorly in proteins' hydration layer and reduce water availability for hydrating unfolding proteins. However, these concepts imply that organic osmolytes are all 'compatible' and interchangeable in this way. Instead, most have unique non-osmotic cytoprotective properties such as antioxidation, and some may have stabilizing features not universal among osmolytes. The latter is exemplified by trimethylamine N-oxide (TMAO), an osmolyte high in chondrichthyans (sharks and rays), and that increases with depth in many marine animals. First, TMAO is the strongest enhancer of protein folding among common osmolytes, but unlike most osmolytes, exhibits some preferential binding with proteins. Second, unlike other common osmolytes such as glycine, TMAO is not found in nature in the absence of a protein destabilizer—notably urea (primary osmolyte of chondrichthyans) and hydrostatic pressure, both counteracted by TMAO. Without a destabilizer, TMAO can over-stabilize proteins causing non-functional aggregates; i.e., it is not 'compatible'. Third, TMAO 'hardens' water structure and reduces water compressibility (again unlike other osmolytes). Under high pressure in the deep sea, these 'piezolyte' properties reduce both protein unfolding and cell volume compression.

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