Some solved and unsolved problems of chemoinformatics

The field of chemoinformatics has developed from different roots, starting in the 1960s. These branches have now merged into a scientific discipline of its own, exchanging ideas and methods across different areas of chemistry. In the last 40 years chemoinformatics has achieved a lot. Without access to the databases in chemistry developed with chemoinformatics methods, modern chemical research would not be able to work at its present high level of competence. However, there are quite a few challenges, such as drug design and understanding the effect of chemicals on human health and on the environment, as well as furthering our knowledge of chemistry and of biological systems, that can benefit from a more intensive use of chemoinformatics methods. Approaches to meet these challenges will be briefly outlined. All this emphasizes that chemoinformatics has matured into a scientific discipline of its own that reaches out to many other chemical fields and will increase in attractiveness to students and researchers.     

Synthesis of fluorinated amino acid derivatives through late-stage deoxyfluorinations

Fluorine chemistry has represented a hot topic in drug research over the last decade. Because of their pharmaceutical potential, fluorine-containing amino acids and related derivatives have acquired high importance among medicinal chemists. Therefore their synthesis and the development of various synthetic methods for these types of molecular scaffolds have gained increasing interest in synthetic organic chemistry. The current review focuses on synthetic protocols towards fluorine-containing amino acid derivatives through late-stage fluorination with various nucleophilic reagents, describing the access of various open-chain and cyclic α-, β-, γ-amino acid derivatives.     

Ketenes in polymer-assisted synthesis

Since its inception, ketene chemistry has developed into a unique and well-established source of useful transformations for conventional synthetic organic chemistry. It is, therefore, not surprising that soon after their movement from the realm of peptide and peptoid libraries to that of small molecules, combinatorial chemists have sought the benefits of ketene chemistry to satisfy their own synthetic needs. The ability of these versatile molecules to undergo reactions with nucleophiles, and to participate in cycloadditions and cyclocondensations, has been utilized for the preparation of diverse heterocyclic compounds, and has added to the advantages of polymer-assisted synthesis for rapid purification. Different types of ketenes and different methods for their generation have been involved, which illustrates the potential diversity of the chemistry. There is now a better grasp of the effect of the fragility of these sometimes transient molecules on the reactions involving solid supports, and this augurs well for the application of some of the more recent developments in ketene chemistry to the generation of small-molecule libraries.     

Sugar amino acid based scaffolds--novel peptidomimetics and their potential in combinatorial synthesis

To meet the growing demands for the development of new molecular entities for discovering new drugs and materials, organic chemists have started looking for new concepts to supplement traditional approaches. In one such approach, the expertise gained over the years in the area of organic synthesis and the rational drug-design concepts are combined together to create "nature-like" and yet unnatural organic molecules that are expected to provide leads in discovering new molecules. Emulating the basic principles followed by nature to build its vast repertoire of biomolecules, organic chemists are developing many novel multifunctional building blocks. Sugar amino acids constitute an important class of such polyfunctional scaffolds where the carboxyl, amino and hydroxyl groups provide an excellent opportunity for organic chemists to create structural diversities akin to nature's molecular arsenal. Recent advances in the area of combinatorial chemistry give unprecedented technological support for rapid compilations of sugar amino acid-based libraries exploiting the diversities of carbohydrate molecules and well-developed solid-phase peptide synthesis methods. This review chronicles the development of sugar amino acids as a novel class of peptidomimetic building blocks and their applications in generating desired secondary structures in peptides as well as in creating mimics of natural biopolymers.     

Organoselenium Chemistry in Stereoselective Reactions

Selenium-based methods have developed rapidly over the past few years asnd organoselenium chemistry has become a very useful tool in the hands of synthetic chemists. The different reactivity of selenium-containing compounds in contrast to the sulfur analogues has led to versatile and new synthetic methods in organic chemistry. Various functionalities can be selectively introduced into complex molecules under very mild reaction conditions. In this review, the principles of organoselenium chemistry are traced back to their origins and are highlighted with respect to stereoselective synthesis. The unique properties of selenium allow the development of new and highly selective transformations, which can be employed subsequently in new routes for the synthesis of versatile chiral building blocks and for natural product synthesis.     

Chemoinformatics: a new field with a long tradition

Chemoinformatics is the application of informatics methods to solve chemical problems. Although this term was introduced only a few years ago, this field has a long history with its roots going back more than 40 years. Work on chemical structure representation and searching, quantitative structure–activity relationships, chemometrics, molecular modeling as well as computer-assisted structure elucidation and synthesis design was initiated in the 1960s. These different origins have now merged into a discipline of its own that is in full bloom. All areas of chemistry from analytical chemistry to drug design can benefit from chemoinformatics methods. And there are still many challenging chemical problems waiting for solutions through the further development of chemoinformatics.     

Simple, high-yield methods for the synthesis of aldehydes directly from o-, m-, and p-carborane and their further conversions

Aldehydes have long served as important building blocks for synthetic chemists, and carboranyl aldehydes are no exception. Recent literature reports, for example, illustrate their application as intermediates in biomedicine, materials science, and basic organic chemistry. We report here new methods for the single-step preparation of C-monoformyl and C,C-diformyl derivatives directly from o-, m-, and p-carborane, as well as improved synthetic routes to homologated carboranyl aldehydes. Additionally, reductive amination is used to transform these aldehydes into a series of 2 degrees amines of alpha-amino acid esters.     

Cover Picture

The cover picture shows that chemical and biological knowledge need to be linked more to ensure that highly effective and target-specific drugs can be found more quickly. Additionally, the main and side effects must be controlled in the best interests of the individual patient. Despite the intensive use of high-throughput technologies in drug research, despite new insight in genomic and proteomic research and in structural biology, and despite the progress made in bio- and chemoinformatics, there is still a worldwide shortage of new and innovative drugs. The bottleneck in lead-structure generation lies in the preparation of new biologically relevant substances and therefore to a major extent in chemistry. The way medicinal chemists perceive their subject and its role in the natural sciences as well as in the value chain of drug research is crucial to counteract this shortage, as explained by Wess et al. on page 3341-3350.     

Transition Metals in the Synthesis and Functionalization of Indoles [New Synthesis Methods (72)]

The use of transition-metal complexes as reagents for the synthesis of complex organic compounds has been under development for at least several decades, and many extraordinary organic transformations of profound potential have been realized. However, adoption of this chemistry by the practicing synthetic organic chemist has been inordinately slow, and only now are transition-metal reagents beginning to achieve their rightful place in the arsenal of organic synthesis. Several factors contributed to the initial reluctance of synthetic organic chemists to use organometallic reagents. Lacking education and experience in the ways of elements having d electrons, synthetic chemists viewed organometallic processes as something mysterious and unpredictable, and not to be discussed in polite society. Organometallic chemists did not help matters by advertising their latest advances as useful synthetic methodology, but restricting their studies to very simple organic systems lacking any serious functionality (e.g., the “methyl, ethyl, butyl, futile” syndrome). Happily, things have changed. Organometallic chemists have turned their attention to more complex systems, and more recently trained organic chemists have benefited from exposure to the application of transition metals. This combination has set the stage for major advances in the use of transition metals in the synthesis of complex organic compounds. This review deals with one aspect of this area, the use of transition metals in the synthesis of indoles.     

Historical Roots of the "Mad Scientist": Chemists in Nineteenth-century Literature

Abstract

This paper traces the historical roots of the "mad scientist," a concept that has powerfully shaped the public image of science up to today, by investigating the representations of chemists in nineteenth-century Western literature. I argue that the creation of this literary figure was the strongest of four critical literary responses to the emergence of modern science in general and of chemistry in particular. The role of chemistry in this story is crucial because early nineteenth-century chemistry both exemplified modern experimental laboratory research and induced, due to its rapid growth, a ramification and fragmentation of knowledge that undermined former ideals of the unity of knowledge under the umbrella of metaphysics and religion. Because most writers considered contemporary chemistry an offspring of "wrong alchemy," all four responses drew on the medieval literary figure of the "mad alchemist" to portray chemists. Whereas early writers considered the quest for scientific knowledge to be altogether in vain, later writers pointed out the narrow-minded goals and views specifically of chemistry. A third response moved that criticism to a metaphysical and religious level, by relating chemistry to materialism, nihilism, atheism and hubris. The fourth response, the "mad scientist," elaborated on the hubris theme by attaching moral perversion to the "mad alchemist."     

Objects of inquiry in classical chemistry: material substances

I argue in the paper that classical chemistry is a science predominantly concerned with material substances, both useful materials and pure chemical substances restricted to scientific laboratory studies. The central epistemological and methodological status of material substances corresponds with the material productivity of classical chemistry and its way of producing experimental traces. I further argue that chemist??s ??pure substances?? have a history, conceptually and materially, and I follow their conceptual history from the Paracelsian concept of purity to the modern concept of pure stoichiometric compounds. The history of the concept of ??pure substances?? shows that modern chemists?? concept of purity abstracted from usefulness rather than being opposed to it. Thus modern chemists?? interest in pure chemical substances does not presuppose a concept of pure science.     

Time-Resolved Photoacoustic Calorimetry: From Carbenes to Proteins

Why have molecules only been seen but not heard? For over a century chemists have probed reactions with various spectroscopic methods to learn about structures, dynamics, and reactivities of their molecules. What they have not done is to listen to their molecules react. Although the photoacoustic phenomenon has been known since 1880, it is only in the last twenty years that technology has developed to the point where sound waves produced by reacting molecules can be time resolved and the information contained within the waves deciphered. The information content within the photoacoustic wave is indeed rich, for one can learn about the dynamics and the magnitude of enthalpy changes associated with the reaction as well as the changes in molecular volume. This review article chronicles the development of time-resolved photoacoustic calorimetry and its application to a variety of reactions encountered in organic and organometallic chemistry and biochemistry.     

Photocatalytic and Electrochemical Borylation and Silylation Reactions

Due to their high versatility borylated and silylated compounds are inevitable synthons for organic chemists. To escape the classical hydroboration/hydrosilylation paradigm, chemists turned their attention to more modern and green methods such as photoredox chemistry and electrosynthesis. This account focuses on novel methods for the generation of boryl and silyl radicals to forge C−B and C−Si bonds from our group.     

Effect of Additives on the Selectivity and Reactivity of Enzymes

Enzymes have been widely used as efficient, eco‐friendly, and biodegradable catalysts in organic chemistry due to their mild reaction conditions and high selectivity and efficiency. In recent years, the catalytic promiscuity of many enzymes in unnatural reactions has been revealed and studied by chemists and biochemists, which has expanded the application potential of enzymes. To enhance the selectivity and activity of enzymes in their natural or promiscuous reactions, many methods have been recommended, such as protein engineering, process engineering, and media engineering. Among them, the additive approach is very attractive because of its simplicity to use and high efficiency. In this paper, we will review the recent developments about the applications of additives to improve the catalytic performances of enzymes in their natural and promiscuous reactions. These additives include water, organic bases, water mimics, cosolvents, crown ethers, salts, surfactants, and some particular molecular additives.     

Collagen and collagen mimetic peptide conjugates in polymer science

Collagen, the most abundant protein in animal kingdom, has attracted scientists in supramolecular chemistry, biomedical and materials science. This review describes the recent developments and progress of collagen mimetic peptide based materials. Research on collagen mimetic peptides was initially developed by biochemists to elucidate the structure and stability of collagen, followed by biologists and polymer chemists to produce nanostructured fibrous scaffolds with collagen mimetic peptides as the building blocks. Modern synthesis methods have been developed and particular ligation chemistries basing on activated ester, click chemistry, carbodiimide chemistry or other ligation chemistries provide versatile methods to prepare collagen–polymer conjugates. These conjugates with collagen mimetic peptides as the building blocks show exciting stimuli responsive or spontaneously assembly behavior. The corresponding synthetic techniques of well-defined collagen architectures and assembly behaviors are discussed in detail in the present review.     

Basic overview of chemoinformatics

There is no particular point in time that determines when chemoinformatics was founded or established. It slowly evolved from several, often quite humble beginnings. Scientists in various fields of chemistry struggled with the development of computer methods which allowed them to manage the enormous amount of chemical information and to find relationships between the structure and properties of a compound. During the 1960s some early developments appeared that led to a flurry of activities in the 1970s. This review provides a general overview of basic methods in the specific fields of chemoinformatics, from encoding chemical compounds, storing and searching data in databases, to generating and analyzing these data. In addition, the chief interconnecting points of chemoinformatics applications are highlighted including the contributions of Johann Gasteiger to this field.     

信息化学研究进展

信息化学（chemoinformatics)作为信息学与传统化学的交叉学科，是当前化学领域上的一个研究热点，本文论述了它的产生背景、理论基础、研究任务，提出了信息化学学科在总体上应具有的三个层次（接口结构），详细地阐明了信息化学的工作方式，并探讨了各个层次和信息采集接口之间的相互关系，最后，我们结合自己的工作预测了信息化学研究今后的发展方向。     

Ball milling in organic synthesis: solutions and challenges

During the last decade numerous protocols have been published using the method of ball milling for synthesis all over the field of organic chemistry. However, compared to other methods leaving their marks on the road to sustainable synthesis (e.g. microwave, ultrasound, ionic liquids) chemistry in ball mills is rather underrepresented in the knowledge of organic chemists. Especially, in the last three years the interest in this technique raised continuously, culminating in several high-quality synthetic procedures covering the whole range of organic synthesis. Thus, the present tutorial review will be focused on the highlights using this method of energy transfer and energy dissipation. The central aim is to motivate researchers to take notice of ball mills as chemical reactors, implementing this technique in everyday laboratory use and thus, pave the ground for future activities in this interdisciplinary field of research.     

Materials and biological applications of 1,2,3-selenadiazoles: a review

In recent years, chemistry of metal-nitrogen–bonded compounds have attracted tremendous attention mainly because of unusual properties resulting from such a bond involving carbon and other heteroatoms. M?N–bonded compounds, when containing group VI elements, especially selenium, has attracted great attention in materials chemistry. In addition, the increased interest in synthesis of N-containing bioactive compounds with other heteroatoms such as selenium, sulfur, etc is mainly because of their tremendous potential as antioxidants, additives, dyes for polymers, and as insecticides, in solvent extraction, and in nanotechnology. Thus, the synthesis and applications of 1,2,3-selenadiazoles have attracted recent interest of materials scientists, including nanotechnologists, pharmaceutical chemists, and organic chemists. The chemistry of 1,2,3-selenadiazoles is highly rich and has been practiced ever since its first report in 1972. Such N-containing Se-heterocycles form several types of selenadiazoles that are a rich source of selenium for semiconductor nanoparticles of metal selenides. The materials chemistry of such molecules has been documented for over three decades, and their great scope in semiconductors has emerged. This review article is an attempt to bring a variety of materials and biological application of 1,2,3-selenadiazoles for better understanding of the researchers.