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Despite decades of ground-breaking research in academia, organic synthesis is still a rate-limiting factor in drug-discovery projects. Here we present some current challenges in synthetic organic chemistry from the perspective of the pharmaceutical industry and highlight problematic steps that, if overcome, would find extensive application in the discovery of transformational medicines. Significant synthesis challenges arise from the fact that drug molecules typically contain amines and N-heterocycles, as well as unprotected polar groups. There is also a need for new reactions that enable non-traditional disconnections, more C–H bond activation and late-stage functionalization, as well as stereoselectively substituted aliphatic heterocyclic ring synthesis, C–X or C–C bond formation. We also emphasize that syntheses compatible with biomacromolecules will find increasing use, while new technologies such as machine-assisted approaches and artificial intelligence for synthesis planning have the potential to dramatically accelerate the drug-discovery process. We believe that increasing collaboration between academic and industrial chemists is crucial to address the challenges outlined here.

Chemical synthesis plays a key role in pharmaceutical research and development. Campos et al. review some of the advantages that have come from recent innovations in synthetic methods. In particular, they highlight small-molecule catalysts stimulated by visible light, enzymes engineered for versatility beyond their intrinsic function, and bio-orthogonal reactions to selectively modify proteins for conjugation. High-throughput techniques are also poised to accelerate methods optimization from small-scale discovery to large-scale production, and complementary machine-learning approaches are just coming into focus. Science , this issue p. eaat0805 Innovations in synthetic chemistry have enabled the discovery of many breakthrough therapies that have improved human health over the past century. In the face of increasing challenges in the pharmaceutical sector, continued innovation in chemistry is required to drive the discovery of the next wave of medicines. Novel synthetic methods not only unlock access to previously unattainable chemical matter, but also inspire new concepts as to how we design and build chemical matter. We identify some of the most important recent advances in synthetic chemistry as well as opportunities at the interface with partner disciplines that are poised to transform the practice of drug discovery and development.

The flavouring, perfume and pharmaceutical industries rely on the selective hydrogenation of α,β-unsaturated aldehydes to generate unsaturated alcohols; here, a new type of highly selective catalyst is described in which platinum nanoparticles are sandwiched between a core and a shell of a metal−organic framework. Sandwich course for catalysts Unsaturated alcohols, widely used in the flavouring, perfume and pharmaceutical industries, are produced by selectively hydrogenating C–O groups over C–C groups present in suitable starting aldehyde molecules. Developing efficient catalysts for this transformation is challenging. Here Zhiyong Tang and colleagues describe a new type of highly selective catalyst in which platinum nanoparticles are sandwiched between a core and a shell of a metal–organic framework. This arrangement results in stable catalysts that selectively hydrogenate C–O groups to produce a range of value-added unsaturated alcohols. The design strategy underpinning the work should be applicable to other selective catalysts for important yet challenging chemical reactions. Owing to the limited availability of natural sources, the widespread demand of the flavouring, perfume and pharmaceutical industries for unsaturated alcohols is met by producing them from α,β-unsaturated aldehydes, through the selective hydrogenation of the carbon–oxygen group (in preference to the carbon–carbon group) 1 . However, developing effective catalysts for this transformation is challenging 2 , 3 , 4 , 5 , 6 , 7 , because hydrogenation of the carbon–carbon group is thermodynamically favoured 8 . This difficulty is particularly relevant for one major category of heterogeneous catalyst: metal nanoparticles supported on metal oxides. These systems are generally incapable of significantly enhancing the selectivity towards thermodynamically unfavoured reactions, because only the edges of nanoparticles that are in direct contact with the metal-oxide support possess selective catalytic properties; most of the exposed nanoparticle surfaces do not 9 , 10 , 11 , 12 , 13 , 14 . This has inspired the use of metal–organic frameworks (MOFs) to encapsulate metal nanoparticles within their layers or inside their channels, to influence the activity of the entire nanoparticle surface while maintaining efficient reactant and product transport owing to the porous nature of the material 15 , 16 , 17 , 18 . Here we show that MOFs can also serve as effective selectivity regulators for the hydrogenation of α,β-unsaturated aldehydes. Sandwiching platinum nanoparticles between an inner core and an outer shell composed of an MOF with metal nodes of Fe 3+ , Cr 3+ or both (known as MIL-101; refs 19 , 20 , 21 ) results in stable catalysts that convert a range of α,β-unsaturated aldehydes with high efficiency and with significantly enhanced selectivity towards unsaturated alcohols. Calculations reveal that preferential interaction of MOF metal sites with the carbon–oxygen rather than the carbon–carbon group renders hydrogenation of the former by the embedded platinum nanoparticles a thermodynamically favoured reaction. We anticipate that our basic design strategy will allow the development of other selective heterogeneous catalysts for important yet challenging transformations.

Knowledge of the three-dimensional structures of proteins and other biological macromolecules often aids understanding of how they perform complicated tasks in the cell. Because many such tasks involve the cleavage or formation of chemical bonds, structural characterization at the atomic level is most useful. Developments in the electron microscopy of frozen hydrated samples (cryo-electron microscopy) are providing unprecedented opportunities for the structural characterization of biological macromolecules. This is resulting in a wave of information about processes in the cell that were impossible to characterize with existing techniques in structural biology.

Macromolecules are essential cellular components in biological systems responsible for performing a large number of functions that are necessary for growth and perseverance of living organisms. Proteins, lipids and carbohydrates are three major classes of biological macromolecules. To predict the structure, function, and behaviour of any cluster of macromolecules, it is necessary to understand the interaction between them and other components through basic principles of chemistry and physics. An important number of macromolecules are present in mixtures with surfactants, where a combination of hydrophobic and electrostatic interactions is responsible for the specific properties of any solution. It has been demonstrated that surfactants can help the formation of helices in some proteins thereby promoting protein structure formation. On the other hand, there is extensive research towards the use of surfactants to solubilize drugs and pharmaceuticals; therefore, it is evident that the interaction between surfactants with macromolecules is important for many applications which includes environmental processes and the pharmaceutical industry. In this review, we describe the properties of different types of surfactants that are relevant for their physicochemical interactions with biological macromolecules, from macromolecules–surfactant complexes to hydrophobic and electrostatic interactions.

Production of anilines—key intermediates for the fine chemical, agrochemical, and pharmaceutical industries—relies on precious metal catalysts that selectively hydrogenate aryl nitro groups in the presence of other easily reducible functionalities. Herein, we report convenient and stable iron oxide (Fe₂O₃)-based catalysts as a more earth-abundant alternative for this transformation. Pyrolysis of iron-phenanthroline complexes on carbon furnishes a unique structure in which the active Fe₂O₃ particles are surrounded by a nitrogen-doped carbon layer. Highly selective hydrogénation of numerous structurally diverse nitroarenes (more than 80 examples) proceeded in good to excellent yield under industrially viable conditions.

The olefin metathesis reaction of two unsaturated substrates is one of the most powerful carbon-carbon-bond-forming reactions in organic chemistry. Specifically, the catalytic olefin metathesis reaction has led to profound developments in the synthesis of molecules relevant to the petroleum, materials, agricultural and pharmaceutical industries. These reactions are characterized by their use of discrete metal alkylidene catalysts that operate via a well-established mechanism. While the corresponding carbonyl-olefin metathesis reaction can also be used to construct carbon-carbon bonds, currently available methods are scarce and severely hampered by either harsh reaction conditions or the required use of stoichiometric transition metals as reagents. To date, no general protocol for catalytic carbonyl-olefin metathesis has been reported. Here we demonstrate a catalytic carbonyl-olefin ring-closing metathesis reaction that uses iron, an Earth-abundant and environmentally benign transition metal, as a catalyst. This transformation accommodates a variety of substrates and is distinguished by its operational simplicity, mild reaction conditions, high functional-group tolerance, and amenability to gram-scale synthesis. We anticipate that these characteristics, coupled with the efficiency of this reaction, will allow for further advances in areas that have historically been enhanced by olefin metathesis.

The converging roles of men and women are among the grandest advances in society and the economy in the last century. These aspects of the grand gender convergence are figurative chapters in a history of gender roles. But what must the \"last\" chapter contain for there to be equality in the labor market? The answer may come as a surprise. The solution does not (necessarily) have to involve government intervention and it need not make men more responsible in the home (although that wouldn't hurt). But it must involve changes in the labor market; especially how jobs are structured and remunerated to enhance temporal flexibility. The gender gap in pay would be considerably reduced and might vanish altogether if firms did not have an incentive to disproportionately reward individuals who labored long hours and worked particular hours. Such change has taken off in various sectors, such as technology, science, and health, but is less apparent in the corporate, financial, and legal worlds.

Cheese whey (CW), the liquid resulting from the precipitation and removal of milk casein during cheese-making, and the second cheese whey (SCW) derived from the production of cottage and ricotta cheeses are the main byproducts of dairy industry. The major constituent of CW and SCW is lactose, contributing to the high BOD and COD content. Because of this, CW and SCW are high-polluting agents and their disposal is still a problem for the dairy sector. CW and SCW, however, also consist of lipids, proteins, and minerals, making them useful for production of various compounds. In this paper, microbial processes useful to promote the bioremediation of CW and SCW are discussed, and an overview on the main whey-derived products is provided. Special focus was paid to the production of health-promoting whey drinks, vinegar, and biopolymers, which may be exploited as value-added products in different segments of food and pharmaceutical industries.

Pharmacy today is a highly remunerated female-majority profession with a small gender earnings gap and low earnings dispersion. Using extensive surveys of pharmacists, as well as the US Census, American Community Surveys, and Current Population Surveys, we explore the gender earnings gap, penalty to part-time work, demographics of pharmacists relative to other college graduates, and evolution of the profession during the last half-century. Technological changes increasing substitutability among pharmacists, growth of pharmacy employment in retail chains and hospitals, and related decline of independent pharmacies reduced the penalty to part-time work and contribute to the narrow gender earnings gap in pharmacy.