Order Parameter of the Liquid–Liquid Transition in a Molecular Liquid

Liquid–liquid transitions (LLTs) between amorphous phases of a single (chemically unchanged) liquid were predicted to occur in most molecular liquids but have only been observed in triphenyl phosphite (TPP) and <i>n</i>-butanol, and even these examples have been dismissed as “aborted crystallization”. One of the foremost reasons that LLTs remain so controversial is the lack of an obvious order parameter, that is, a physical parameter characterizing the phase transition. Here, using the technique of fluorescence lifetime imaging, we show for the first time that the LLT in TPP is characterized by a change in polarity linked to changes in molecular ordering associated with crystal polymorphs. We conclude that the LLT in TPP is a phase transition associated with frustrated molecular clusters, explaining the paucity of examples of LLTs seen in nature

Monitoring the Uptake and Redistribution of Metal Nanoparticles during Cell Culture Using Surface-Enhanced Raman Scattering Spectroscopy

We describe the uptake of silver nanoparticles by CHO (Chinese hamster ovary) cells and their subsequent fate as a result of cell division during culture, as monitored by surface-enhanced Raman scattering (SERS) spectroscopy. Mapping of populations of cells containing both labeled and native nanoparticles by SERS spectroscopy imaging provided a quantitative method by which the number of intracellular nanoparticles could be monitored. Initially, for a given amount of nanoparticles, the relationship between the number taken up into the cell and the time of incubation was explored. Subsequently, the redistribution of intracellular nanoparticles upon multiple rounds of cell division was investigated. Intracellular SERS signatures remained detectable in the cells for up to four generations, although the abundance and intensity of the signals declined rapidly as nanoparticles were shared with daughter cells. The intensity of the SERS signal was dependent both on stability of the label and their abundance (nanoparticle aggregation increases the extent of the SERS enhancement). The data show that while the labeled nanoparticles remain stable for prolonged periods, during cell division, the changes in signal could be attributed both to a decrease in abundance and distribution (and hence aggregation)

Copper(II) Binding to Amyloid-β Fibrils of Alzheimer’s Disease Reveals a Picomolar Affinity: Stoichiometry and Coordination Geometry Are Independent of Aβ Oligomeric Form

Cu2+ ions are found concentrated within senile plaques of Alzheimer’s disease patients directly bound to amyloid-β peptide (Aβ) and are linked to the neurotoxicity and self-association of Aβ. The affinity of Cu2+ for monomeric Aβ is highly disputed, and there have been no reports of affinity of Cu2+ for fibrillar Aβ. We therefore measured the affinity of Cu2+ for both monomeric and fibrillar Aβ(1−42) using two independent methods: fluorescence quenching and circular dichroism. The binding curves were almost identical for both fibrillar and monomeric forms. Competition studies with free glycine, l-histidine, and nitrilotriacetic acid (NTA) indicate an apparent (conditional) dissociation constant of 10−11 M, at pH 7.4. Previous studies of Cu-Aβ have typically found the affinity 2 or more orders of magnitude weaker, largely because the affinity of competing ligands or buffers has been underestimated. Aβ fibers are able to bind a full stoichiometric complement of Cu2+ ions with little change in their secondary structure and have coordination geometry identical to that of monomeric Aβ. Electron paramagnetic resonance studies (EPR) with Aβ His/Ala analogues suggest a dynamic view of the tetragonal Cu2+ complex, with axial as well as equatorial coordination of imidazole nitrogens creating an ensemble of coordination geometries in exchange between each other. Furthermore, the N-terminal amino group is essential for the formation of high-pH complex II. The Aβ(1−28) fragment binds an additional Cu2+ ion compared to full-length Aβ, with appreciable affinity. This second binding site is revealed in Aβ(1−42) upon addition of methanol, indicating hydrophobic interactions block the formation of this weaker carboxylate-rich complex. A Cu2+ affinity for Aβ of 1011 M−1 supports a modified amyloid cascade hypothesis in which Cu2+ is central to Aβ neurotoxicity

Polyamorphism Mirrors Polymorphism in the Liquid–Liquid Transition of a Molecular Liquid

Liquid–liquid transitions between two amorphous phases in a single-component liquid have courted controversy. All known examples of liquid–liquid transitions in molecular liquids have been observed in the supercooled state, suggesting an intimate connection with vitrification and locally favored structures inhibiting crystallization. However, there is precious little information about the local molecular packing in supercooled liquids, meaning that the order parameter of the transition is still unknown. Here, we investigate the liquid–liquid transition in triphenyl phosphite and show that it is caused by the competition between liquid structures that mirror two crystal polymorphs. The liquid–liquid transition is found to be between a geometrically frustrated liquid and a dynamically frustrated glass. These results indicate a general link between polymorphism and polyamorphism and will lead to a much greater understanding of the physical basis of liquid–liquid transitions and allow the systematic discovery of other examples

Chiral Quantum Metamaterial for Hypersensitive Biomolecule Detection

Chiral biological and pharmaceutical molecules are analyzed with phenomena that monitor their very weak differential interaction with circularly polarized light. This inherent weakness results in detection levels for chiral molecules that are inferior, by at least six orders of magnitude, to the single molecule level achieved by state-of-the-art chirally insensitive spectroscopic measurements. Here, we show a phenomenon based on chiral quantum metamaterials (CQMs) that overcomes these intrinsic limits. Specifically, the emission from a quantum emitter, a semiconductor quantum dot (QD), selectively placed in a chiral nanocavity is strongly perturbed when individual biomolecules (here, antibodies) are introduced into the cavity. The effect is extremely sensitive, with six molecules per nanocavity being easily detected. The phenomenon is attributed to the CQM being responsive to significant local changes in the optical density of states caused by the introduction of the biomolecule into the cavity. These local changes in the metamaterial electromagnetic environment, and hence the biomolecules, are invisible to “classical” light-scattering-based measurements. Given the extremely large effects reported, our work presages next generation technologies for rapid hypersensitive measurements with applications in nanometrology and biodetection