Antibody-drug conjugates (ADCs) have achieved remarkable clinical success and are now firmly established as a major therapeutic modality among antibody-based medicines. ADCs are generally defined as constructs in which highly potent cytotoxic small-molecule drugs are covalently linked to antibodies via chemical linkers. Continuous efforts in both academia and industry have been devoted to improving their stability, controllable drug release, and overall therapeutic index.

This review provides an overview of recent progress in ADC research, with particular emphasis on the roles that organic synthetic chemistry can play in advancing the field. By highlighting innovations in linker design, payload optimization, and site-specific conjugation strategies, this article aims to present future perspectives on ADC development from the standpoint of organic chemistry.

Organic fluorescent dyes are essential to optoelectronic devices and molecular imaging, but practical use demands simultaneous optimization of absorption/emission, quantum yield, environmental responsiveness, photostability, processability, and biocompatibility. This account outlines an integrated design strategy that combines elucidation of excited-state structures and deactivation pathways in π-electronic frameworks, theoretical prediction of emission behavior, and modern synthetic functionalization. Using robust π-platforms with finely tuned donor/acceptor motifs and conformational control, minimalist dyes and liquid-crystalline materials were developed with high matrix compatibility and strong application performance. Solvatochromic fluorophores were engineered to maintain high quantum yields while exhibiting large, continuous polarity-dependent color shifts, enabling sensitive mapping of membrane microenvironments and low-toxicity long-term live-cell imaging. Further advances include near-infrared-excitable two-photon dyes for deep-tissue observation and probes that selectively detect trihalomethanes via coupled fluorescence signaling and photodecomposition. For aggregation-induced emission (AIE), catalytic C-N cross-coupling provided access to highly twisted amino-substituted polycyclic aromatics, yielding bright, viscosity-responsive AIEgens. Mechanistic studies established a guiding principle: AIE can be rationally created by designing efficient solution-phase deactivation through conical-intersection access, rather than relying solely on rotational restriction.

Given the recent rapid advances in computational technology, kinetic modeling of chemical reactions has emerged as a powerful technique for reaction analysis and control. Meanwhile, detailed understanding of reactions and processes is an upcoming issue in modern process development in the pharmaceutical industry. Since the quality by design (QbD) approach has been introduced by ICH guidelines, predictive and quantitative reaction analysis is expected in designing chemical process by regulatory agencies, to achieve better quality-controlled medication and social acceptance. Consequently, numerical simulation utilizing reaction kinetic model is attracting broad interest due to its unique capability of extrapolation in prediction rooted in the nature of physical model. However, the kinetic modeling and simulation of organic reactions remain significantly more challenging than modeling efforts in other fields that utilize well-established physical or semi-empirical models, since these require ‘full-scratch’ model building based on a detailed theoretical and experimental understanding of rate laws for each chemical reaction, which inherently have unique mechanisms, namely, unknown models. In this paper, extensive example of practical application of kinetic modeling and simulation in reaction development and scale-up based on physical organic chemistry approach are presented, particularly from the aspect as a tool for synthetic organic chemists.

We developed a Pd(0)/TPPMS-catalyzed benzylation of a variety of nucleophiles using benzyl alcohols in water. In the first section of this account, we demonstrate that π-benzylpalladium species enable an N-benzylation/benzylic C-H benzylation cascade applicable to a wide range of aromatic amines, affording the corresponding dibenzylated products. The initially formed N-benzylated intermediates can react with π-benzylpalladium complexes to generate bis(π-benzyl)palladium intermediates. In this process, the nucleophilic η¹-σ-benzyl ligand attacks the electrophilic η³-π-benzyl ligand to form a new benzylic C-C bond. In the second section, we apply this catalytic system to the N-benzylation reaction via the borrowing hydrogen methodology. Because electron-deficient nucleophiles such as 2-aminopyridines are unreactive toward the electrophilic π-benzylpalladium intermediate, Tsuji-Trost-type benzylation does not proceed. Instead, the palladium species reacts with benzyl alcohol, initiating a borrowing hydrogen process through dehydrogenation. In the third section, we demonstrate the direct use of benzylic alcohols in a multicomponent reaction of isatoic anhydrides with amines in water, providing an efficient synthetic route to a series of 2-arylquinazolinones.

Now that increasing number of techniques for polymerizations have been developed, one can easily access various polymers with well-defined primary structures by controlled/living polymerization systems. However, the environmental issues caused by polymeric material have also become a serious problem nowadays. To dissolve these problems, now it should be considered that the beneficial materials from birth to grave. Bio-based polymer materials from renewable resources have also recently been attracting much attention from the viewpoint of environmentally benign and sustainable chemistry, i.e., reducing our reliance on fossil fuels. The specific or complicated structures originating from natural products are also definitely beneficial for developing high performance or functional bio-based polymeric materials. In this study, the controlled/living polymerizations of a series of naturally-occurring and/or -derived vinyl monomer are presented for creating novel bio-based polymers. We also tried to synthesize novel degradable polymers that decomposes upon a specific stimulus by using the chemistry of controlled/living polymerization.