The primary function of the cell membrane is to protect cells from their surroundings. This entails a strict regulation on controlling the exchange of matter between the cell and its environment. A key factor when considering potential biological applications of a particular chemical structure has to do with its ability to internalize into cells. Molecules that can readily cross cell membranes are frequently needed in biological research and medicine, since most therapeutic entities are designed to modulate intracellular components. However, the design of molecules that do not penetrate cells is also relevant toward, for example, extracellular contrast agents, which are most widely used in clinical diagnosis. Small molecules have occupied the forefront of biomedical research until recently, but the past few decades have seen an increasing use of larger chemical structures, such as proteins or nanoparticles, leading to unprecedented and often unexpectedly novel research. Great achievements have been made toward understanding the rules that govern cellular uptake, which show that cell internalization of molecules is largely affected by their size. For example, macromolecules such as proteins and nucleic acids are usually unable to internalize cells. Intriguingly, in the case of nanoparticles, larger sizes seem to facilitate internalization via endocytic pathways, through which the particles remain trapped in lysosomes and endosomes. In this Account, we aimed at presenting our personal view of how different chemical structures behave in terms of cell internalization due to their size, ranging from small drugs to large nanoparticles. We first introduce the properties of cell membranes and the main mechanisms involved in cellular uptake. We then discuss the cellular internalization of molecules, distinguishing between those with molecular weights below 1 kDa and biological macromolecules such as proteins and nucleic acids. In the last section, we review the biological behavior of nanoparticles, with a special emphasis on plasmonic nanoparticles, which feature a high potential in the biomedical field. For each group of chemical structures, we discuss the parameters affecting their cellular internalization but also strategies that can be applied to achieve the desired intracellular delivery. Particular attention is paid to approaches that allow conditional regulation of the cell internalization process using external triggers, such as activable cell penetrating peptides, due to the impact that these systems may have in drug delivery and sensing applications. The Account ends with a “Conclusions and Outlook” section, where general lessons and future directions toward further advancements are briefly presented.

Groovy chiral gold particles: Although plasmonic optical activity can arise from chiral assemblies of gold and silver nanoparticles, there are few examples of gold nanoparticles with intrinsic chirality and high optical activity. González-Rubio et al. show that morphological chirality can be induced during the seeded growth of gold nanoparticles, particularly for highly anisotropic nanorods. Chiral additives as cosurfactants formed helical micelles that directed the seeded growth to create grooves that maintained a chiral morphology. The resulting particles displayed high-intensity circular dichroism with anisotropy factors near 0.2 at near-infrared wavelengths. Science , this issue p. 1472

Dendrimers constitute a distinctive category of synthetic materials that bear resemblance to proteins in various aspects, such as discrete structural organization, globular morphology, and nanoscale dimensions. Remarkably, these attributes coexist with the capacity for facile large-scale production. Due to these advantages, the realm of dendrimers has undergone substantial advancement since their inception in the 1980s. Numerous reviews have been dedicated to elucidating this subject comprehensively, delving into the properties and applications of quintessential dendrimer varieties like PAMAM, PPI, and others. Nevertheless, the contemporary landscape of dendrimers transcends these early paradigms, witnessing the emergence of a diverse array of novel dendritic architectures in recent years. In this review, we aim to present a comprehensive panorama of the expansive domain of dendrimers. As such, our focus lies in discussing the key attributes and applications of the predominant types of dendrimers existing today. We will commence with the conventional variants and progressively delve into the more pioneering ones, including Janus, supramolecular, shape-persistent, and rotaxane dendrimers.

Fascinating properties are displayed by synthetic multicomponent supramolecular systems that comprise a manifold of competitive interactions, thereby mimicking natural processes. We present the integration of two reentrant phase transitions based on an unexpected dilution-induced assembly process using supramolecular polymers and surfactants. The co-assembly of the water-soluble benzene-1,3,5-tricarboxamide (BTA-EG ₄ ) and a surfactant at a specific ratio yielded small-sized aggregates. These interactions were modeled using the competition between self-sorting and co-assembly of both components. The small-sized aggregates were transformed into supramolecular polymer networks by a twofold dilution in water without changing their ratio. Kinetic experiments show the in situ growth of micrometer-long fibers in the dilution process. We were able to create systems that undergo fully reversible hydrogel-solution-hydrogel-solution transitions upon dilution by introducing another orthogonal interaction.

Selective anion extraction is useful for the recovery and purification of valuable chemicals, and in the removal of pollutants from the environment. Here we report that Fe^II₄L₄ cage 1 is able to extract an equimolar amount of ReO₄⁻, a high‐value anion and a nonradioactive surrogate of TcO₄⁻, from water into nitromethane. Importantly, the extraction was efficiently performed even in the presence of 10 other common anions in water, highlighting the high selectivity of 1 for ReO₄⁻. The extracted guest could be released into water as the cage disassembled in ethyl acetate, and then 1 could be recycled by switching the solvent to acetonitrile. The versatile solubility of the cage also enabled complete extraction of ReO₄⁻ (as the tetrabutylammonium salt) from an organic phase into water by using the sulfate salt of 1 as the extractant.

Discrete palladium (II) complexes featuring purposely designed phosphine ligands can promote depropargylation and deallylation reactions in cell lysates. The performance of these complexes is superior to that of other palladium sources, which apparently are rapidly deactivated in such hostile complex media. This good balance between reactiv-ity and stability allows the use of these discrete phosphine palladium complexes in living mammalian cells, whereby they can mediate similar transformations. The presence of a phosphine ligand in the coordination sphere of palladi-um also provides for the introduction of targeting groups, such as hydrophobic phosphonium moieties, which facili-tate the accumulation of the complexes in mitochondria.