Louis Pasteur,Chemist: An Account of His Studies of Cinchona Alkaloids

Pasteur carried out pioneering work on cinchona alkaloids and their derivatives and his studies led to important discoveries. He examined crystals of cinchona alkaloids for his correlation of crystal hemihedrism with molecular chirality, studies that led Pasteur to the discovery of physicochemical differences between diastereoisomeric salts of tartaric acids with optically active cinchona bases, an important insight into fundamentals of molecular chirality. These physicochemical differences also led to Pasteur’s invention of the vital method of racemate resolution through diastereoisomeric derivatives. Pasteur clarified the confusion around the cinchona alkaloids by elucidating their identities and relations. He discovered the conversion of the major cinchona alkaloids to quinicine and cinchonicine, a finding subsequently of considerable importance in studies of the structure and synthesis of the major cinchona alkaloids. The reaction producing quinicine and cinchonicine led Pasteur to the discovery of the racemization of tartaric acid and the finding of meso‐tartaric acid, fundamental breakthroughs in the development of stereochemistry.     

Mechanical and Chemical Explanations in Du Clos' Chemistry

Abstract

Samuel Cottereau Du Clos (1598–1685) appears as the first French chemist to combine in chemistry (for him, the science of substances, the physics of qualities) demonstrations using the laws of motion with demonstrations using the qualities of chemical principles. In this way, he brought to bear two different and complementary orders of explanation. According to Du Clos, the mechanical considerations represent a first approach, a stage towards the knowledge of “the truth of things” (la vérité des choses) in natural philosophy. He set out his chemistry at the Académie royale des sciences de Paris, especially through his criticism of Boyle's Certain Physiological Essays in 1668–1669.     

Molecular Chirality in Chemistry and Biology: Historical Milestones

Beginning early in the 19th century, developments in crystallography, optics, and chemistry in France set the stage for the discovery of molecular chirality by Louis Pasteur in 1848. He found that the crystallization of the sodium ammonium salt of ‘paratartaric acid’, a mysterious ‘isomer’ of natural (+)‐tartaric acid (TA), produced two different crystal types that were non‐superimposable mirror‐image forms of each other. He separated the two types and found their optical rotations in solution opposite in direction and equal in absolute magnitude. This led him to conclude that paratartaric acid is a combination of two mirror‐image molecule types of TA that are ‘dissymmetric’, an existing term he adapted to the connotation of today's ‘chiral’. In 1857, he found that the two enantiomers of TA were metabolized by a microorganism at drastically different rates, and thereby discovered biological enantioselectivity. In 1886, Italian chemist Arnaldo Piutti discovered D ‐asparagine and found that it tasted intensely sweet, in contrast to the known L ‐asparagine which had no taste. This was the discovery of stereoselectivity at biological receptors. As a result of advances in stereoselective synthesis and enantioselective chromatography during the last decades of the 20th century, in the 1990s the importance of molecular chirality in drug action and disposition began to receive serious attention from drug‐regulatory authorities and the pharmaceutical industry, the overall result of which has been the near‐complete disappearance of racemic drugs as newly introduced pharmaceuticals.     

The Story Behind the Link between Molecular Chirality and Crystal Shape

Here we describe the story behind the link between molecular chirality and macroscopic phenomena, the latter being a probe for the direct assignment of absolute configuration of chiral molecules. First, a brief tour of the history of molecular stereochemistry, starting with the classic experiment reported by Pasteur in 1848 on the separation of enantiomorphous crystals of a salt of tartaric acid, and his conclusion that the molecules of life are chiral of single-handedness. With time, this study raised, inter alia, two fundamental questions: the absolute configuration of chiral molecules and how a molecule of given configuration shapes the enantiomorphous morphology of its crystal. As for the first question, following the beginning of crystal structure determination by X-ray diffraction in 1912, it took almost 40 years before Bijvoet assigned molecular chirality through the esoteric method involving anomalous X-ray scattering. We have been able to address and link both questions through ‘everyday concepts of left and right’ (in the words of Jack Dunitz) by the use of ‘tailor-made’ auxiliaries. By such means, it proved possible to reveal, through morphology, etch patterns, epitaxy and symmetry reduction of both chiral and, paradoxically, centrosymmetric crystals, the basic chiral symmetry of the molecules of life, the α-amino acids and sugars.     

Enlightenment Chemistry Translated by a Brazilian Man of Science in Lisbon

Abstract

The Brazilian-born man of science Martim Francisco de Andrada (1775–1844) actively participated in some of the major publishing activities of the Portuguese Enlightenment, notably in the Arco do Cego printing house. For many Brazilians, technical and scientific activities provided a path to becoming part of the administrative system of the Portuguese Empire. This paper examines Andrada’s work as translator of Torbern Bergman’s book Sciagraphia Regni Mineralis, secundum principia proxima digesti, originally published in Latin in 1782 and soon translated into French. A comparison between the Portuguese and French editions allows us to understand the different ways in which translators intervened in texts. Martim Francisco established a dialogue both with Bergman and with his translators, Jean-André Mongez and Jean-Claude Delamétherie, in addition to the challenge of having to deal with the propositions set forward by the new pneumatic chemistry. We argue that the Brazilian translator’s main objective was to explore the possibilities of using the book as a teaching and fieldwork manual. From this perspective, the resulting translation gains significance when read at the confluence of these demands and intentions.     

Meet the Board of ChemistryOpen: Sheshanath V. Bhosale

Sheshanath V. Bhosale received his PhD from Freie University Berlin (Germany) in supramolecular chemistry under the supervision of Prof. J. H. Fuhrhop in 2004. He then pursued his postdoctoral studies with Prof. S. Matile at University of Geneva (Switzerland) under the auspices of a Roche Foundation Fellowship. This was followed by a stay at Monash University (Australia) for 5 years as an ARC-APD Fellow. He worked at RMIT University, Melbourne (Australia) for 6 years as ARC-Future Fellowship. Currently, Prof. Bhosale is working at the Department of Chemistry, Goa University (India) as a UGC-FRP Professor, His research interests lie in the design and synthesis of π-functional materials, especially small molecules, for sensing, biomaterials, and supramolecular chemistry applications. So far, Prof. Bhosale has produced 185 research articles and his work has been cited more than 4400 times, giving him an h-index of 32. He currently serves as an active Editorial Board member for ChemistryOpen.     

Structure and Dynamics of Chiral Molecules

Could there be chiral methane? What is the characteristic structural feature (in a physicochemical sense) of a molecule? This question dates back to Louis Pasteur, the discoverer of molecular chirality, and since the work of van't Hoff and Le Bel is generally considered by chemists as solved. In the present article it is pointed out that there exist fundamentally conflicting theoretical views of the physical origin of molecular chirality. These views predict consequences that could, in principle, be distinguished experimentally, but at present there is no conclusive experimental evidence available. Possible experiments are suggested that test different hypotheses. The importance of the magnitude of the parity-violating energy difference δE_PV in molecules due to the weak nuclear force for both the structure and spectra of chiral molecules and for the kinetics of racemization is discussed. The chemical relaxation rate coefficient of chiral molecules with some appreciable energy of excitation is derived for several limiting cases of a simple statistical mechanical model, which takes ΔE_PV into account.     

Mechanical and chemical explanations in Du Clos' chemistry

Samuel Cottereau Du Clos (1598-1685) appears as the first French chemist to combine in chemistry (for him, the science of substances, the physics of qualities) demonstrations using the laws of motion with demonstrations using the qualities of chemical principles. In this way, he brought to bear two different and complementary orders of explanation. According to Du Clos, the mechanical considerations represent a first approach, a stage towards the knowledge of "the truth of things" (la vérité des choses) in natural philosophy. He set out his chemistry at the Académie royale des sciences de Paris, especially through his criticism of Boyle's Certain Physiological Essays in 1668-1669.     

Dynamic Covalent Chemistry within Biphenyl Scaffolds: Reversible Covalent Bonding,Control of Selectivity,and Chirality Sensing with a Single System

Axial chirality is a prevalent and important phenomenon in chemistry. Herein we report a combination of dynamic covalent chemistry and axial chirality for the development of a versatile platform for the binding and chirality sensing of multiple classes of mononucleophiles. An equilibrium between an open aldehyde and its cyclic hemiaminal within biphenyl derivatives enabled the dynamic incorporation of a broad range of alcohols, thiols, primary amines, and secondary amines with high efficiency. Selectivity toward different classes of nucleophiles was also achieved by regulating the distinct reactivity of the system with external stimuli. Through induced helicity as a result of central‐to‐axial chirality transfer, the handedness and ee values of chiral monoalcohol and monoamine analytes were reported by circular dichroism. The strategies introduced herein should find application in many contexts, including assembly, sensing, and labeling.     

Dynamic Covalent Chemistry within Biphenyl Scaffolds: Reversible Covalent Bonding,Control of Selectivity,and Chirality Sensing with a Single System

Axial chirality is a prevalent and important phenomenon in chemistry. Herein we report a combination of dynamic covalent chemistry and axial chirality for the development of a versatile platform for the binding and chirality sensing of multiple classes of mononucleophiles. An equilibrium between an open aldehyde and its cyclic hemiaminal within biphenyl derivatives enabled the dynamic incorporation of a broad range of alcohols, thiols, primary amines, and secondary amines with high efficiency. Selectivity toward different classes of nucleophiles was also achieved by regulating the distinct reactivity of the system with external stimuli. Through induced helicity as a result of central‐to‐axial chirality transfer, the handedness and ee values of chiral monoalcohol and monoamine analytes were reported by circular dichroism. The strategies introduced herein should find application in many contexts, including assembly, sensing, and labeling.     

August Kekulé—The Architect of Chemistry Commemorating the 150th Anniversary of His Birth

Imagination, daring, and critical understanding are the sources of the impulses still felt today which chemistry received from the theoretical studies of Kekulé. “Let us learn to dream, gentlemen, then perhaps we shall discover the truth; but let us beware of publishing our dreams abroad before they have been scrutenized by our vigilant intellect … Let us always allow the fruit to hang until it is ripe. Unripe fruit brings even the grower but little profit; it damages the health of those who consume it; it endangers particularly the youth which cannot yet distinguish between ripe and unripe.” (Kekulé 1890).     

Purification of Enantiomeric Mixtures in Enantioselective Synthesis: Overlooked Errors and Scientific Basis of Separation in Achiral Environment

The syntheses of optically active compounds (whether of pharmaceutical or synthetic importance, or as promising candidates as chiral ligands and auxiliaries in asymmetric syntheses) result in the formation of a mixture of products with one enantiomer predominating. Usually, the practice is to use standard open‐column chromatography for the first purification step in an enantioselective synthesis; the workup of the reaction product by crystallization or achiral chromatography would mask the real efficiency of the enantioselective methodology, since enantiomeric ratio (er) of the product may change by any of these methods. Most of the synthetic organic chemists are aware of the influence of crystallization on the er value. Majority of synthetic organic chemists are, however, not aware, while employing standard chromatography, that there may be an increase or decrease of er value. In other words, an undesired change in er goes unnoticed when such a mixture of enantiomers is isolated by chromatography on an achiral‐phase because of the prevalent concept of basic stereochemistry. Such unnoticed errors in enantioselective reactions may lead to misinterpretations of the enantioselective outcome of the synthesis. The scientific issue is, what is the difference between a racemic and nonracemic mixture in achiral environment (e.g., achiral‐phase chromatography) that leads to enantiomeric enrichment, amounting to separation of one particular enantiomer? There are sporadic reports on enantiomer separation of nonracemic mixtures in an achiral environment particularly from the scientists working in analytical chemistry. To cover/discuss all these reports is out of the scope of this article. The aim of the present report is to draw attention to the following points: i) How should the synthetic organic chemists and analytical chemists take care of the unexpected separation of enantiomers from nonracemic mixtures in a totally achiral environment? ii) What are the technical terms used in recent literature? iii) The requirement of revisiting definitions/terms (introduced in recent years, in particular) to describe such separations of enantiomers in light of prevalent scientific/chemical terminology used in the ‘language of chemistry’, the text book concept, and IUPAC background. iv) To propose logical scientific terminology or phrases for explaining the possible mechanism of separation under these conditions. v) To discuss briefly the concept/possibile phenomenon responsible for these enantioselective effects. It is also attempted to explain the effect of change of physical parameters influencing the separation from nonracemic mixture in achiral‐phase chromatography.     

Chemical applications of topology and group theory. XXII : Lowest degree chirality polynomials for regular polyhedra [1]

The lowest degree chirality polynomials for the regular octahedron, cube, and regular icosahedron are discussed. All three of these regular polyhedra are chirally degenerate since they have more than one lowest degree chiral ligand parition by the Ruch-Schönhofer scheme. The two lowest degree chirality polynomials for the octahedron have degree 6 and can be formed from three degree 3 generating polynomialsf,g, andh through the relationshipsf(g +h) andf(g –h), wheref,g, andh measure the effects of the three separating reflection planes (h), the four threefold rotation axes, and the three fourfold rotation axes, respectively. The permutation groups of the vertices of the cube and icosahedron contain only even permutations, which leads to a natural pairing of their chiral ligand partitions according to equivalence of the corresponding Young diagrams upon reflection through their diagonals. The two lowest degree chirality polynomials for the cube have degree 4 and can be formed from two degree 4 generating polynomialsf andg through the relationships –2g andf –2g, wheref andg measure the effects of theS ₆ improper rotation andC ₄, proper rotation axes. respectively. The four lowest degree chiral ligand partitions for the icosahedron have degree 4 and lead naturally to a single degree 4 chirality polynomial with 120 terms of the general type (x –y)² (z –w)². This chirality polynomial for the icosahedron cannot be broken down into simpler generating polynomials, in contrast to the lowest degree chirality polynomials for the octahedron and cube. This appears to relate to the origin of the icosahedral group from the simple alternating groupA ₅. The full icosahedral chirality polynomial can be simplified to give a chirality polynomial for the chiral boron-monosubstituted ortho and meta carboranes of the general formula B₂C₁₀H₁₁X.     

Artificial Neural Networks for Guest Chirality Classification through Supramolecular Interactions

A novel strategy for classification of guest chirality based on the combination of artificial neural networks and anion‐receptor chemistry is reported. The receptor reported herein forms supramolecular complexes with a variety of biologically important carboxylates, in which the chemical shift changes during addition of anions result in complex guest‐stereochemistry‐dependent patterns as followed by ¹H NMR spectroscopy. The neural network had learnt these patterns from a training set of 12 anions, and successfully identified the “unknown” chirality of 14 guests present in the test set. Additionally, principal component analysis could discriminate most of the guests studied (26) and allowed for identification of the receptor protons, which are responsible for information transfer of guest chirality.     

Stereochemical language in supramolecular polymer chemistry: How we can do better

Stereochemical nomenclature remains a point of attention; especially now different fields in chemistry become more and more entwined. The ubiquitously used terminology “amplification of chirality” is fundamentally incorrect, as chirality cannot be amplified. Instead, we now recommend “amplification of asymmetry” as an alternative in the field of (supramolecular) polymer chemistry. Amplification of asymmetry refers to the increase of the magnitude of the asymmetry in the enantiomeric composition either at the molecular or the supramolecular level, and covers observations of nonproportional increase in optical activity in helical (supramolecular) polymers and in high enantiomeric excesses found when nonlinear effects are operative in asymmetric catalysis.     

Joseph Louis Gay-Lussac (1778-1850) and analytical chemistry

On the occasion of Joseph Louis Gay-Lussac's 200th anniversary, after a short comprehensive review of his scientific activities and his life, his achievements in the field of analytical chemistry are discussed. Gay-Lussac extensively studied the reaction of hydrogen sulphide with different metals and consequently may be considered the founder of classical qualitative analysis. He developed titrimetry into a scientific method. He designed the first burette that became widespread in use. The terms burette and pipette were created by him. The combustion apparatus designed by him together with Thénard was the starting point for organic elemental carbon-hydrogen analysis.     

The Total Synthesis of Brevetoxin B: A Twelve-Year Odyssey in Organic Synthesis

The total synthesis of brevetoxin B has been achieved recently after a long search for a suitable pathway. This twelve-year odyssey

1 The Odyssey of Homer, translated by R. Lattimore, Harper Perenial, New York, 1975 . Homer's Odyssey, one of the western world's first two poems (the Iliad is the other), is the tale of the adventures, wanderings, and exploits of Odysseus, a Greek hero of the Trojan war, as he attempts to reach Ithaca, his home island where his wife Penelope awaits him. During his journey Odysseus has an incredible series of adventures and setbacks caused by the anger of the god Poseidon, whose son Odysseus had blinded. Finally, assisted by his patroness, the goddess Athene, Odysseus returns home to Ithaca to find and punish the suitors, evil men who tried to win his wife's hand and who squandered his wealth and corrupted his servants while he was away. Telemachus, Odysseus' son, who had his own share of adventures while growing up, facing the suitors and, looking for his father, joins him in glory and wisdom as they reestablish their throne on Ithaca. Besides Odysseus, other main characters of Odyssey are as follows: Telemachus: The son of Odysseus, who is just entering manhood, is highly conscious of his duties as a prince successor to the throne and protector of his mother as well as the need to live up to his father's reputation as a hero. His actions waver between the immature and the well-thought over as he searches for the truth about his father and desperately appeals to others for help. It is not until towards the end of the story that he exhibits great courage, skills, and confidence and one feels that he is, indeed, the son of Odysseus. Athene: She is the daughter of Zeus, goddess of wisdom, and patroness of arts and crafts. Odysseus is her favorite and protegé and she is his heroine, even though she is a goddess. She plays a leading role in all important events in the narrative, and her spirit and power always influence and assist Odysseus and Telemachus in their difficult moments. A friend and a confidant to Odysseus, she enjoys winning him over and her relationship with him, while the hero adores her and finds special comfort, companionship, and understanding in her. Poseidon: Younger brother to Zeus, god of the sea and of earthquakes, father of Polyphenus the one-eyed Cyclops whom Odysseus blinds. As a ruler of the sea and natural phenomena, Poseidon is able to place many obstacles in front of Odysseus, whom he despises. Poseidon, however, is unable to hold out against the combined pressure of the other gods, particularly Athene, of whom Odysseus is a favorite, and so eventually relents, but not before he repeatedly unleashes his anger. The Cyclops, Scylla, and The Sirens: Some of the superhuman and monstrous characters of the tale who inflicted tremendous tortures and blows at Odysseus and his men, before he finally overcame them. The Suitors: The evil noblemen of Ithaca who attempt to undermine Odysseus, win the hand of his queen, Penelope, and corrupt his palace servants. They succeed partly, wasting away a great deal of Odysseus fortune, but he eventually prevails and punishes them. Ithaca: The island kingdom of Odysseus, most likely located somewhere off the western coast of Greece and the destination of the hero in this adventure. It is interesting to compare places, events, and characters from the Odyssey to those of modern-day total synthesis, an excercise left to the imagination of the reader!

in synthetic organic chemistry was marked by several strategic and tactical routes, and resulted in numerous new synthetic methods. This article is a behind-thescenes account of the total synthesis of brevetoxin B, from its origins at the University of Pennsylvania to its completion at the University of California, San Diego, and The Scripps Research Institute, La Jolla, California.     

Stereoselective Aldol Addition to Rhenium(I) Complexes and Reversible Dimerization with Epimerization of the Metal Center

Herein, we report several examples of stereoselective aldol additions of aldehydes or ketones to Re^I tricarbonyl complexes to form monomeric derivatives in good yields. The metal‐centered chirality defines the final stereochemistry of the carbon atom of the monomeric Re^I complex after the addition. However, it cannot control the resulting stereochemistry of the enolate part, and thus, if the α‐carbon atom of the reagent is prochiral, a mixture of diastereoisomers is obtained. On the other hand, all of the monomeric complexes can be reversibly dimerized in basic media to form cis dimers, for which an epimerization of the metal‐centered chirality is required in order to avoid steric congestion. All of these results are supported by exhaustive crystallographic analysis.