The homochirality of biomolecules remains one of the outstanding puzzles concerning the beginning of life. Chiral amplification of a randomly perturbed racemic mixture of chiral molecules is a well-accepted prerequisite for all routes to biological homochirality 1-6 . Some models have suggested that such amplification occurred due to asymmetric discrimination of chiral biotic/prebiotic molecules when they adsorbed onto crystalline surfaces 7-9 . While chiral amplification has been demonstrated on surfaces of both chiral and achiral crystals 10-15 , the mechanism that would produce an enantiomeric imbalance in the chiral surfaces themselves has not been addressed. Here we report strong chiral amplification in the colloidal synthesis of intrinsically chiral lanthanide phosphate nanocrystals, quantitatively measured via the circularly polarized luminescence of the lanthanide ions within the nanocrystals. The amplification involves spontaneous symmetry breaking into either left-or right-handed nanocrystals below a critical temperature. Furthermore, chiral tartaric acid molecules in the solution act as an external "chiral field", sensitively directing the amplified nanocrystal handedness through a discontinuous transition between left-and right-handed excess. These characteristics suggest a conceptual framework for chiral amplification, based on the statistical thermodynamics of Corresponding authorsCorrespondence to Gil Markovich. SUPPLEMENTARY INFORMATIONX-ray diffraction data of the NCs, NC seeded growth experiments, calculation of number of TA molecules adsorbed on the seed particles, discussion on the origin of the NCs' CPL, the NCs' glum values, results of syntheses without stirring, and hysteresis behavior in the NC ee vs. h curves.

The occurrence of biological homochirality is attributed to symmetry breaking mechanisms which are still debatable 1 . Studies of symmetry breaking require tools for monitoring the population ratios of individual chiral nano-objects, such as molecules, polymers or nanocrystals. Moreover, mapping their spatial distributions may elucidate on their symmetry breaking mechanism. Recently, researchers have utilized differential scattering or circular dichroism microscopy to identify chirality on individual plasmonic nanostructures and inorganic nanocrystals 2-7 .However, these measurements are prone to optical system artifacts. While luminescence is preferred for detecting single particle chirality, the typical low optical activity of chromophores limits its applicability 8,9 . Here, we report on handedness determination of single chiral lanthanide based nanocrystals, using circularly polarized luminescence, with a total photon count of 2×10 4 . We also utilize a machine learning approach 10 for correlative Corresponding authorCorrespondence to Ori Cheshnovsky.

The chiral aspect of inorganic crystals that crystallize in chiral space groups has been largely ignored until recently, partly due to difficulties in characterizing the chiroptical properties of bulk crystals, and also due to the difficulty in separating (sub)micrometer‐scale chiral crystal enantiomers. In recent years, the colloidal synthesis of intrinsically chiral nanocrystals (NCs) of several chiral inorganic compounds with significant enantiomeric excess has been demonstrated. This is achieved through the use of chiral molecular ligands, which bind to the atomic/ionic components of the crystals, preferentially forming one crystal enantiomorph. Here, recent progress on several aspects of these NCs is described, including the connection between ligand structure and its ability to direct NC handedness, chiral amplification in the synthesis leading to enantiopure NC samples, spontaneous symmetry breaking, the formation of NCs with chiral shapes, the connection between lattice and shape chirality and mixed contributions of atomic‐scale and shape chirality to the chiroptical properties.

Enzyme-responsive polymeric micelles have great potential as drug delivery systems due to the high selectivity and overexpression of disease-associated enzymes, which could be utilized to trigger the release of active drugs only at the target site. We previously demonstrated that enzymatic degradation rates of amphiphilic PEG-dendron hybrids could be precisely tuned by gradually increasing the hydrophobic to hydrophilic ratio. However, with the increase in hydrophobicity, the micelles rapidly became too stable and could not be degraded, as often encountered for many other amphiphilic assemblies. Here we address the challenge to balance between stability and reactivity of enzymatically degradable assemblies by utilizing reversible dimerization of diblock polymeric amphiphiles to yield jemini amphiphiles. This molecular transformation serves as a tool to control the critical micelle concentration of the amphiphiles in order to tune their micellar stability and enzymatic degradability. To demonstrate this approach, we show that simple dimerization of two polymeric amphiphiles through a single reversible disulfide bond significantly increased the stability of their micellar assemblies toward enzymatic degradation, although the hydrophilic to hydrophobic ratio was not changed. Reduction of the disulfide bond led to dedimerization of the polymeric hybrids and allowed their degradation by the activating enzyme. The generality of the approach is demonstrated by designing both esterase- and amidase-responsive micellar systems. This new molecular design can serve as a simple tool to increase the stability of polymeric micelles without impairing their enzymatic degradability.

Enyzme-responsive polymeric assemblies hold great potential for biomedical applications due to the over-expression of disease-associated enzymes, which can be utilized to activate such systems only in afflicted tissues. Herein we demonstrate that the overall molecular weight of polymeric amphiphiles, which have the same hydrophilic/hydrophobic ratio, can be tuned to create polymeric micelles with an extreme range of degradation rates. This approach expands the available set of molecular parameters that can be adjusted to tune the degradation rate of polymeric assemblies, paving new possibilities for rational design of polymeric systems with controlled degradation rates.