Protein inactivation by reactive oxygen species (ROS) such as singlet oxygen ((1)O2) and superoxide radical (O2(•-)) is considered to trigger cell death pathways associated with protein dysfunction; however, the detailed mechanisms and direct involvement in photodynamic therapy (PDT) have not been revealed. Herein, we report Ir(III) complexes designed for ROS generation through a rational strategy to investigate protein modifications by ROS. The Ir(III) complexes are effective as PDT agents at low concentrations with low-energy irradiation (≤ 1 J cm(-2)) because of the relatively high (1)O2 quantum yield (> 0.78), even with two-photon activation. Furthermore, two types of protein modifications (protein oxidation and photo-cross-linking) involved in PDT were characterized by mass spectrometry. These modifications were generated primarily in the endoplasmic reticulum and mitochondria, producing a significant effect for cancer cell death. Consequently, we present a plausible biologically applicable PDT modality that utilizes rationally designed photoactivatable Ir(III) complexes.

The development of cost-effective and environmentally friendly photocatalysts and photosensitizers has received tremendous attention because of their potential utilization in solar-light-harvesting applications. In this respect, carbon dots (CDs) prepared by bottom-up methods have been considered to be promising light-harvesting materials. Through their preparation from various molecular precursors and synthetic methods, CDs exhibit excellent optical and charge-transfer properties. Furthermore, their photophysical properties can be readily optimized and enhanced by means of doping, functionalization, and post-synthetic treatment. In this review, we summarize the recent progress in CDs synthesized using bottom-up approaches. These CDs exhibit strong light absorption and unique electron donor/acceptor capabilities for light-harvesting applications. We anticipate that this review will provide new insights into novel types of photosensitizers and photocatalysts for a wide range of applications.

Traditional single-molecule methods do not report whole-molecule kinetic conformations, and their adaptive shape changes during the process of self-assembly. Here, using graphene liquid-cell electron microscopy with electrons of low energy at low dose, we show that this approach resolves the time dependence of conformational adaptations of macromolecules for times up to minutes, the resolution determined by motion blurring, with DNA as the test case. Single-stranded DNA molecules are observed in real time as they hybridize near the solid surface to form double-stranded helices; we contrast molecules the same length but differing in base-pair microstructure (random, blocky, and palindromic hairpin) whose key difference is that random sequences possess only one stable final state, but the others offer metastable intermediate structures. Hybridization is observed to couple with enhanced translational mobility and torsion-induced rotation of the molecule. Prevalent transient loops are observed in error-correction processes. Transient melting and other failed encounters are observed in the competitive binding of multiple single-stranded molecules. Among the intermediate states reported here, some were predicted but not observed previously, and the high incidence of looping and enhanced mobility come as surprises. The error-producing mechanisms, failed encounters, and transient intermediate states would not be easily resolved by traditional single-molecule methods. The methods generalize to visualize motions and interactions of other organic macromolecules.