Homunuclus

Church teaching holds that in-vitro fertilization is morally wrong because it replaces the conjugal union between husband and wife and often results in the destruction of embryos. Artificial insemination for married couples is allowable if it "facilitates" the sex act but does not replace it. The church condemns all forms of experimentation on human embryos.Vatican Critical of Stem Cell Creation

The current pope was once Cardinal Ratzinger the Vatican's chief Inquisitor, yes I know we weren't expecting the Spanish Inquistion.

When the issue of cloning and artificial life was presented for JP2, Ratzinger issued the churches statement on bio-ethics which has not changed since the Rennisance when the Church banned sorcery and the creation of artificial life known as the Homunculus And indeed Ratzinger in his paper, refers to cloning as creating a homonucleus. 21st Century science meets the middle ages.

Does the law permit the ìenhancementî or other manipulation of one's genetic outfit? In this context, the following issues were discussed at the seminar: reproduction techniques in general (the "homunculus issue," see Goethe's Faust 11), special issues of "reprogenetics," cloning (inherently wrong, or open to an evaluation between healing effects and human dignity by way of a rule-and- exception relationship?), disease prevention (MV, cancers), unfairly advantaging certain children in view of a "level playing field" of genetic outfits, right of parents to genetically manipulate their offspring, and liability of parents who do not manipulate.The New Genetics and the Law

The crowning example of alchemical hybris came with the claim of pseudo-Paracelsus in the sixteenth century that he could make a homunculus - an artificial man. Like the gold of the alchemists, which was said to exceed the 24 carats of the best natural gold, the homunculus was supposed to be better than a natural man. Being made in a flask from human semen,
he was free of the catamenial substance that, according to the current theories of generation, supplied the material basis to an ordinary fetus. According to pseudo-Paracelsus, the homunculus was a semi-spiritual being that had an immediate apprehension of all the arts and a preternatural intelligence. In modern terms, the homunculus could be called the perfect test-tube baby, engineered to have the highest possible intelligence quota and aptitude. I have written an article focusing on this topic ("The Homunculus and his Forebears," 1999; see Vita), and have a book focusing on alchemy and the art-nature debate under contract (Promethean Ambitions: Alchemy and the Refashioning of Nature, forthcoming with University of Chicago Press). Newton's Alchemy, recreated

What can we make of his account of the creation of a homunculus, a
miniature human being, in his laboratory? Cloning and genetic engineering are clearly impossible with 16th-century technology. Paracelsus

The invention of hand lenses and the microscope facilitated studies of the chick embryo by Marcello Malpighi (1628-1694), but also gave rise to one of the most profound errors in describing human development, that of the homunculus. This was a miniature human believed to have been seen within the head of a human spermatozoon and which presumed to enlarge when deposited in the female. This was the basis of the preformation theory and was believed by many well into the 18th century.lifeissues.net | When Does Human Life Begin? The Final Answer

Drawing of Human Spermatozoa
1694
The drawing was conceived by Niklaas Hartsoeker not by what
he had seen, but what he presumed would be visible if sperm
could be adequately viewed.

Consider the profound difficulty embryonic development presents to an observer. A complex organism, such as a chick, frog, insect or human, arises in an orderly and magical way from an apparently structureless egg. When embryology was in its infancy in the 17th and 18th centuries, the thought was that no animal could arise from such nothingness. Thus was born the theory of the homunculus: the idea that an infinite set of tiny individuals were contained, one within another, in each egg—or in each sperm (there was vigorous disagreement as to which). Development was seen as the visible unfolding of a preexisting individual. Unhappily for this wonderful notion, in the late 18th century Caspar Friedrich Wolff showed by microscopy that embryos contained cells but no homunculus—there was no preformed entity.
American Scientist Online - In the Twinkle of a Fly

U.S. Senator Sam Brownback (R-Kansas) recently told his fellow Republicans he would advance a two-year moratorium rather than a permanent ban. Ironically, Brownback relayed his intentions while President Bush reaffirmed his opposition to human embryo cloning in a speech delivered by satellite to the Southern Baptist Convention in St. Louis. Bush told them, "We believe that a life is a creation, not a commodity, and that our children are gifts to be loved and protected, not products to be designed and manufactured by human cloning." How did we get so quickly from a few cells in a dish to children? It reminds me of artists' representations during the Middle Ages of the homunculus: an invisibly tiny, fully formed human carried around by the male and then deposited in the female during intercourse. The tiny homunculus would eventually grow into a fetus before it was born. Those were the days before the discoveries of the microscope, sperm and egg. So then maybe Bush and Bevilacqua imagine that people still reproduce with homunculi. Otherwise, describing what we know with absolute certainty are nothing more than single or several cells in a microscopic cluster, resembling the cells inside your cheek, as "children" simply doesn't make any sense! If these men didn't wield so much power, we'd laugh at their ignorance. Stem Cells and Cloning: What Bush Doesn't Know Might Kill You ...

Faust and Homunculus
19th century engraving of Goethe's Faust and Homunculus



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21ST CENTURY ALCHEMY

Stanford researchers unveil new material infused with gold in an exotic chemical state

Peer-Reviewed Publication

STANFORD UNIVERSITY

For the first time, Stanford researchers have found a way to create and stabilize an extremely rare form of gold that has lost two negatively charged electrons, denoted Au2+. The material stabilizing this elusive version of the valued element is a halide perovskite—a class of crystalline materials that holds great promise for various applications including more-efficient solar cells, light sources, and electronics components.

Surprisingly, the Au2+ perovskite is also quick and simple to make using off-the-shelf ingredients at room temperature.

"It was a real surprise that we were able to synthesize a stable material containing Au2+—I didn't even believe it at first," said Hemamala Karunadasa, associate professor of chemistry at the Stanford School of Humanities and Sciences and senior author of the study published Aug. 28 in Nature Chemistry. "Creating this first-of-its-kind Au2+ perovskite is exciting. The gold atoms in the perovskite bear strong similarities to the copper atoms in high-temperature superconductors, and heavy atoms with unpaired electrons, like Au2+, show cool magnetic effects not seen in lighter atoms."

"Halide perovskites possess really attractive properties for many everyday applications, so we've been looking to expand this family of materials," said Kurt Lindquist, the lead author of the study who conducted the research as a Stanford doctoral student and is now a postdoctoral scholar in inorganic chemistry at Princeton University. "An unprecedented Au2+ perovskite could open some intriguing new avenues."

Heavy electrons in gold

As an elemental metal, gold has long been valued for its relative scarcity as well as its unmatched malleability and chemical inertness—meaning it can be easily shaped into jewelry and coins that do not react with chemicals in the environment and tarnish over time. An additional key reason for its value is gold's namesake color; arguably no other metal in its pure state has such a distinctively rich hue.

The fundamental physics behind gold's acclaimed appearance also explains why Au2+ is so rare, Karunadasa explained. 

The root reason is relativistic effects, originally postulated in Albert Einstein's famed theory of relativity. "Einstein taught us that when objects move very fast and their velocity approaches a significant fraction of the speed of light, the objects get heavier,” Karunadasa said.

This phenomenon applies to particles, too, and has profound consequences for “massive” heavy elements, such as gold, whose atomic nuclei boast a large number of protons. These particles collectively exert immense positive charge, forcing negatively charged electrons to whirl around the nucleus at breakneck speeds. As a consequence, the electrons grow heavy and tightly surround the nucleus, blunting its charge and allowing outer electrons to drift farther than in typical metals. This rearrangement of electrons and their energy levels leads to gold absorbing blue light and therefore appearing yellow to our eye.

Because of the arrangement of gold's electrons, thanks to relativity, the atom naturally occurs as Au1+ and Au3+, losing one or three electrons, respectively, and spurning Au2+. (The “2+” indicates a net positive charge from the loss of two negatively charged electrons, and the "Au" chemical symbol for gold hails from “aurum,” the Latin word for gold.)

A squeeze of vitamin C

With just the right molecular configuration, Au2+ can endure, the Stanford researchers found. Lindquist said he "stumbled upon" the new Au2+-harboring perovskite while working on a broader project centered on magnetic semiconductors for use in electronic devices.

Lindquist mixed a salt called cesium chloride and Au3+-chloride together in water and added hydrochloric acid to the solution "with a little vitamin C thrown in," he said. In the ensuing reaction, vitamin C (an acid) donates a (negatively charged) electron to the common Au3+ forming Au2+. Intriguingly, Au2+ is stable in the solid perovskite but not in solution.

"In the lab, we can make this material using very simple ingredients in about five minutes at room temperature," said Lindquist. "We end up with a powder that's very dark green, nearly black, and is surprisingly heavy because of the gold it contains."

Recognizing that they may have hit new chemistry paydirt, so to speak, Lindquist performed numerous tests on the perovskite, including spectroscopy and X-ray diffraction, to investigate how it absorbs light and to characterize its crystal structure. Stanford research groups in physics and chemistry led by Young Lee, professor of applied physics and of photon science, and Edward Solomon, the Monroe E. Spaght Professor of Chemistry and professor of photon science, further contributed to studying the behavior of Au2+.

The experiments ultimately bore out the presence of Au2+ in a perovskite and, in the process, added a chapter to a century-old story of chemistry and physics involving Linus Pauling, who received the Nobel Prize in Chemistry in 1954 and the Nobel Peace Prize in 1962. Early in his career, he worked on gold perovskites containing the common forms Au1+ and Au3+. Coincidentally, Pauling also later studied the structure of vitamin C—one of the ingredients required to yield a stable perovskite containing the elusive Au2+.

"We love Linus Pauling’s connection to our work," Karunadasa said. "The synthesis of this perovskite makes for a good story."

Looking ahead, Karunadasa, Lindquist, and colleagues plan to study the new material further and tweak its chemistry. The hope is that an Au2+ perovskite can be used in applications that require magnetism and conductivity as electrons hop from Au2+ to Au3+ in the perovskite.

"We're excited to explore what an Au2+ perovskite could do," Karunadasa said.

Karunadasa is also a senior fellow at the Precourt Institute for Energy and a principal investigator and faculty scientist at the Stanford Institute for Materials and Energy Sciences, SLAC National Accelerator Laboratory. Solomon is a professor of photon science at Stanford Synchrotron Radiation Lightsource, SLAC. Additional Stanford co-authors are Christina R. Deschene and Alexander J. Heyer, graduate students in the Department of Chemistry; and Jiajia Wen, a staff scientist at SLAC. Additional co-authors include Armin Eghdami and Alexander G. Smith, graduate students in the Department of Physics, University of California-Berkeley, and Jeffrey B. Neaton, professor of physics at the University of California-Berkeley; and Dominic H. Ryan, professor of physics at McGill University.

The research was funded in part by the U.S. National Science Foundation, the U.S. Department of Energy, the Fonds de recherche du Québec–Nature et technologies, and the Natural Sciences and Engineering Research Council Canada.

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JOURNAL

Nature Chemistry

DOI

10.1038/s41557-023-01305-y 

ARTICLE TITLE

Stabilizing Au2+ in a mixed-valence 3D halide perovskite

21ST CENTURY ALCHEMY

Techniques honed by Kansas nuclear physicists helped detect creation of gold in Large Hadron Collider collisions

University of Kansas

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ALICE experiment at CERN's Large Hadron Collider, where KU nuclear physicists helped detect gold, briefly, during ultra-peripheral collisions. 

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Credit: CERN

LAWRENCE — Nuclear physicists working at the Large Hadron Collider recently made headlines by achieving the centuries-old dream of alchemists (and nightmare of precious-metals investors): They transformed lead into gold.

At least for a fraction of a second. The scientists reported their results in Physical Reviews.

The accomplishment at the Large Hadron Collider, the 17-mile particle accelerator buried under the French-Swiss border, happened within a sophisticated and sensitive detector called ALICE, a scientific instrument roughly the size of a McMansion.

It was scientists from the University of Kansas, working on the ALICE experiment, who developed the technique that tracked “ultra-peripheral” collisions between protons and ions that made gold in the LHC.

“Usually in collider experiments, we make the particles crash into each other to produce lots of debris,” said Daniel Tapia Takaki, professor of physics and leader of KU’s group at ALICE. “But in ultra-peripheral collisions, we’re interested in what happens when the particles don’t hit each other. These are near misses. The ions pass close enough to interact — but without touching. There’s no physical overlap.”

The ions racing around the LHC tunnel are heavy nuclei with many protons, each generating powerful electric fields. When accelerated, these charged ions emit photons — they shine light.

“When you accelerate an electric charge to near light speeds, it starts shining,” Tapia Takaki said. “One ion can shine light that essentially takes a picture of the other. When that light is energetic enough, it can probe deep inside the other nucleus, like a high-energy flashbulb.”

The KU researcher said during these UPC “flashes” surprising interactions can occur, including the rate event that sparked worldwide attention.

“Sometimes, the photons from both ions interact with each other — what we call photon-photon collisions,” he said. “These events are incredibly clean, with almost nothing else produced. They contrast with typical collisions where we see sprays of particles flying everywhere.”

However, the ALICE detector and the LHC were designed to collect data on head-on collisions that result in messy sprays of particles.

“These clean interactions were hard to detect with earlier setups,” Tapia Takaki said. “Our group at KU pioneered new techniques to study them. We built up this expertise years ago when it was not a popular subject.”

These methods allowed for the news-making discovery that the LHC team transmuted lead into gold momentarily via ultra-peripheral collisions where lead ions lose three protons (turning the speck of lead into a gold speck) for a fraction of a second.

Tapia Takaki’s KU co-authors on the paper are graduate student Anna Binoy; graduate student Amrit Gautam; postdoctoral researcher Tommaso Isidori; postdoctoral research assistant Anisa Khatun; and research scientist Nicola Minafra.

The KU team at the LHC ALICE experiment plans to continue studying the ultra-peripheral collisions. Tapia Takaki said that while the creation of gold fascinated the public, the potential of understanding the interactions goes deeper.

“This light is so energetic, it can knock protons out of the nucleus,” he said. “Sometimes one, sometimes two, three or even four protons. We can see these ejected protons directly with our detectors.”

Each proton removed changes the elements: One gives thallium, two gives mercury, three gives gold.

“These new nuclei are very short-lived,” he said. “They decay quickly, but not always immediately. Sometimes they travel along the beamline and hit parts of the collider — triggering safety systems.”

That’s why this research matters beyond the headlines.

“With proposals for future colliders even larger than the LHC — some up to 100 kilometers in Europe and China — you need to understand these nuclear byproducts,” Tapia Takaki said. “This ‘alchemy’ may be crucial for designing the next generation of machines.”

This work was supported by the U.S. Department of Energy Office of Science, Office of Nuclear Physics.

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DOI

10.1103/PhysRevC.111.054906 

21ST CENTURY ALCHEMY

Biologists, chemical engineers collaborate to reveal complex cellular process inside petunias

Peer-Reviewed Publication

PURDUE UNIVERSITY

 

IMAGE: A PURDUE UNIVERSITY TEAM LED BY NATALIA DUDAREVA, DISTINGUISHED PROFESSOR OF BIOCHEMISTRY IN PURDUE’S COLLEGE OF AGRICULTURE, AND JOHN MORGAN, PROFESSOR IN THE DAVIDSON SCHOOL OF CHEMICAL ENGINEERING, HAVE PUBLISHED NEW DETAILS ABOUT MOLECULAR PROCESSES THAT ALLOW PETUNIAS TO EMIT SCENT CHEMICALS CALLED VOLATILE ORGANIC COMPOUNDS. view more 

CREDIT: PURDUE AGRICULTURAL COMMUNICATIONS/TOM CAMPBELL

Biologists, chemical engineers collaborate to reveal complex cellular process inside petunias

Once upon a time, prevailing scientific opinion might have pronounced recently published research in Nature Communications by a team of Purdue University scientists as unneeded. Now, climate change implications have heightened the need for this line of research.

Flowers emit scent chemicals called volatile organic compounds (VOCs). Earlier this year, the Purdue team published the paper identifying for the first time a protein that plays a key role in helping petunias emit volatiles. The article was selected for the “plants and agriculture” section of the journal’s editors’ highlights webpage.

Natalia Dudareva, who led the study, and her longtime collaborator John Morgan had suggested years ago in grant proposals that molecular processes could be involved in VOC emission. Both times the grant reviewers said there was nothing to look for because simple diffusion was the answer.

“We failed twice because people did not believe us,” said Dudareva, director of the Center for Plant Biology and Distinguished Professor of Biochemistry. “We decided we have to have proof that it’s not simple diffusion, that molecular mechanisms are involved.”

The new work builds on findings that the Dudareva-Morgan collaboration announced in 2015 and 2017 showing how biology helps control the release of scent compounds from plants. The latest paper, chiefly funded by the National Science Foundation and the U.S. Department of Agriculture, focuses on how volatiles cross the cell wall, the barrier that separates the cellular interior from a plant’s outermost protective layer, the cuticle.

“We were looking at whether or not there are proteins that facilitate the transport of these small organic molecules across the cell wall layer,” said Morgan, a professor of chemical engineering.

“The best analogy is to the transport of oxygen in muscle tissue by a protein called myoglobin.”

Volatile organic chemicals are small molecules that have low water solubility. The cell wall, however, is a water-filled environment. This slows the diffusion rate of VOCs because their concentrations cannot build up very high.

“What happens is a protein can bind a lot of these molecules inside a non-waterlike cavity, and it improves or increases the net transport rate,” Morgan explained.

The work has significant practical implications, ranging from the health of the planet to industrial operations. Plants now emit 10 billion metric tons of carbon annually, a quantity that will increase with continued global warming. Floral volatiles also help to protect plants against environmental stresses and are heavily used in the cosmetics industry and in aromatherapy.

“And our diet depends on insect-pollinated plants,” Dudareva said. With global warming, flowers may start blooming earlier, before insects are ready to begin pollination.

The team’s 2015 paper published in the journal Trends in Plant Science reported calculations that had determined the concentration of volatiles needed to sustain the experimentally measured floral emission rate. The concentration reached the millimolar range, a scale that chemists use to quantify substances containing huge numbers of molecules or atoms.

“These compounds will accumulate inside membranes and such high concentration will destroy membranes and destroy the cell,” Dudareva said. This left a clear-cut conclusion: simple diffusion would be impossible.

The initial work had been calculated for snapdragons. But the Purdue researchers focused on petunias for their latest study because, unlike snapdragons, they can be genetically modified to study how particular genes affect the emission process.

“It’s much easier to work with petunias because emission is high, especially during the night,” said Pan Liao, a lead co-author and former Purdue postdoctoral scientist, now an assistant professor of biology at Hong Kong Baptist University. “The emission is strongly regulated in a diurnal pattern.”

Additional co-authors were Itay Maoz, a former Purdue postdoctoral scientist now of Israel’s Agricultural Research Organization; Meng-Ling Shih, PhD 2022, chemical engineering; Xing-Qi Huang, a postdoctoral scientist working in Dudareva’s lab; and Ji Hee Lee, a graduate student in biochemistry. The co-authors contributed a complementary blend of skills and expertise to the work that has become a hallmark of the longstanding collaboration between the Dudareva and Morgan research groups.

Dudareva’s group generated the transgenic plants and handled the cellular biology needed to determine whether a given protein contributes to the volatile emissions. There is no way, however, to detect the level of proteins in a cell or how their concentration changes across a cell wall.

It then fell to Morgan’s group to perform the calculations that quantified the protein contributions and conduct computer simulations to verify the experimental data.

“It’s important to have feedback between the modeling predictions and the actual data,” Morgan said. “Sometimes it starts with the data, then we go do math, and then we go back and compare to the data.”

Xing-Qi Huang, a postdoctoral scientist in the Dudareva laboratory, tags a petunia that will bloom in the next 24 hours. Researchers select flowers that have just bloomed to extract volatiles at their peak.

Ji Hee Lee, a graduate student in biochemistry, prepares an experiment to extract floral volatiles from fresh petunia blooms.

Petunia placed in a glass container in preparation for extraction of floral volatiles.

CREDIT

Purdue Agricultural Communications/Tom Campbell

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JOURNAL

Nature Communications

DOI

10.1038/s41467-023-36027-9 

METHOD OF RESEARCH

Experimental study

SUBJECT OF RESEARCH

Not applicable

ARTICLE TITLE

Emission of floral volatiles is facilitated by cell-wall non-specific lipid transfer proteins

21ST CENTURY ALCHEMY

Mashing molecules: An innovative solution towards greener pharmaceuticals

IMPACTIVE is a project funded by Horizon Europe to study the possibilities of mechanochemistry in the synthesis of active pharmaceutical ingredients. This initiative counts on 17 partners in academia and industry working together towards greener chemistry

Grant and Award Announcement

AGATA COMUNICACIÓN CIENTÍFICA SL

 

IMAGE: SOMEONE MASHING INGREDIENTS IN A MORTAR, MUCH LIKE MECHANOCHEMISTRY USES MECHANOCHEMICAL TO DRIVE CHEMICAL REACTIONS WITHOUT SOLVENTS, PROVIDING A GREENER APPROACH TO THE SYNTHESIS OF PHARMACEUTICALS. view more 

CREDIT: IMPACTIVE

The European Commission has awarded IMPACTIVE almost €7.7 million to reinvent and reinforce the pharmaceutical supply chain. Currently, the production of drugs is associated with high levels of carbon emissions, as well as other environmental impacts linked to the excessive production of chemical waste. IMPACTIVE, a collaboration led by the University of Montpellier, in France, envisions an efficient and simple solution: mechanochemistry. 

Mechanochemistry is a method that mashes molecules together, using ball mills. The mechanical force drives the chemical reactions with high efficacy and low cost. The main advantage of mechanochemistry is its independency of solvents, usually the basis of all traditional reactions and often linked to the generation of high quantities of toxic waste. In fact, currently the manufacture of 1 kilogram of active pharmaceutical ingredients (APIs) is unavoidably linked with almost 200 kilograms of waste. The elimination of solvents from synthesis and purification could minimise the ecological impact of industrial chemistry.

The most recent results report that mechanochemistry could reduce ecotoxicity and carbon emissions by up to 85% and, at the same time, optimise production costs by 12%. Already studied in small laboratory scales and used in production plants in fields like plastic production and materials’ manufacturing, mechanochemistry is now ready for the pharmaceutical industry. IMPACTIVE will study the synthesis of three families of API, and develop pilot production process ready for scale up. On top with key leaders in the field from academia and industry, the project also counts on two partners in the pharmaceutical industry – Novartis and Merck. This interdisciplinary collaboration will facilitate and accelerate the commercial implementation of the technology.

Beyond ball mills, the partners in IMPACTIVE will investigate other mechanochemical methods, more suitable for the scales required by pharmaceutical manufacturers. Among others, this will include twin-screw extrusion, resonant acoustic mixing and spray drying – all of which have showcased an interesting potential in preliminary studies. 

“Overall, mechanochemistry avoids high temperatures and hazardous solvents, providing a more environmentally friendly alternative that reduces waste, and maximizes efficiency,” explains IMPACTIVE coordinator Evelina Colacino, based at the University of Montpellier. “These concepts constitute gold standards of green chemistry and the circular economy, and IMPACTIVE wants to transfer them to the European pharmaceutical landscape,” she adds. 

Moreover, cost reduction and efficient manufacturing could help Europe tackle the current fragility of the supply chain, linked to severe shortages in drugs and pharmaceuticals. Mechanochemistry could become a key tool to improve crisis preparedness and API development during emergencies, thanks to innovative production processes and excellent efficiency. 

IMPACTIVE grows on the success of two previous projects, in particular COST Action CA18112 ‘Mechanochemistry for Sustainable Industry’, also funded by the European Union, which helped establish efficient networks of researchers, innovators and industry leaders working in mechanochemistry. In the future, IMPACTIVE partners plan to become a reference in the field as well, further contributing to cross-collaboration between academia and industry to boost the possibilities of greener manufacturing methods with mechanochemistry.

Mechanochemistry will ensure cost reduction and efficient manufacturing to help Europe tackle the current fragility of the supply chain, linked to severe shortages in drugs and pharmaceuticals. 

 

Several pills on a colourful background. Mechanochemistry could become a key tool to improve crisis preparedness and API development during emergencies, thanks to innovative production processes and excellent efficiency.

CREDIT

Impactive

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IMPACTIVE will study the synth [IMAGE] | EurekAlert! Science News Releases

IMPACTIVE is a big project, funded by the European Commission through its Horizon Europe programme. It’s led by the University of Montpellier, in France, and counts on seventeen partners from nine EU countries, as well as Switzerland and Israel. The consortium includes universities, research centres, industry leaders and SMEs, i.e.:

• University of Montpellier, France
• SATT Axlr, France
• Radboud Universiteit, Netherlands
• Université Catholique de Louvain, Belgium
• Taltech, Estonia
• BAM Institut, Germany
• RWTH Aachen University, Germany
• Max Planck Institut für Kohlenforschung, Germany
• Trinity College Dublin, Ireland
• Technion, Israel
• Center for Colloid and Surface Science (Universities of Cagliari, Parma and Salerno), Italy
• IST-ID, Portugal
• DES-Solutio, Portugal
• AGATA Comunicación Científica, Spain
• Haute École Spécialisée de Suisse Occidentale (HES·SO), Switzerland
• MERCK, Switzerland
• Novartis, Switzerland

 21ST CENTURY ALCHEMY

Gold battles cancer

Organogold(III) complex accumulates in mitochondria of lung cancer cells

Wiley

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Precious metals are not merely ornaments; they are also important components of pharmaceuticals, like the antitumor drug cisplatin. Recently, the search for alternatives with improved activity has begun to focus on gold. In the journal Angewandte Chemie, a French research team has now published the first study about the speciation and distribution of an organogold(III) complex in cancer cells and reveals how specially designed “organogold” complexes might open exciting avenues for fighting cancer.

Gold has a unique electronic structure giving it exceptional chemical traits that translate into subtle interactions with biological molecules. Yet, to date, we have little information about how gold(III) complexes with antitumor activity behave in a biological environment. Do they change? Are they reduced to gold (I) or metallic gold? Where in the cell do they attack? Researchers led by Benoît Bertrand, Michèle Salmain, Sylvain Bohic, and Jean-Louis Hazemann at Sorbonne Université, the Université Grenoble Alpes, CNRS, INSERM, and the European Synchrotron Research Facility, have now carried out a comprehensive study on the chemical reactivity and antitumor activity of various gold(III) complexes. They used a combination of different methods based on synchrotron X-ray radiation—very intensive, bundled flashes of light produced in particle accelerators.

Common to all the complexes they examined (cationic biphenyl gold(III) complexes with aryl, alkyl, and diphosphine helper ligands, known as [(C^C)Au(P^P)]+ cations) is a gold atom bonded to two carbon atoms of the first ligand and two phosphorus atoms of the second, clasping like two sets of tongs. The analyses demonstrate that all the complexes examined were stable in both cell-free environments and inside lung cancer cells. They were not reduced and did not release their ligands to form new bonds.

The complexes were demonstrated to be toxic against tumor cells. A “dppe complex” (biphenyl gold(III) complex with 1,2-diphenylphosphinoethane (dppe) ligand) was the most active. The team used a special setup of synchrotron cryo-X-ray nanoanalysis to “map” elements including gold in frozen-hydrated lung cancer cells with nanometer-scale resolution and locate the dppe complex. It was found to accumulate selectively in the mitochondria, the “powerhouses” of the cells. The advantage of this method is that no labeling, which could distort the result, is needed. This gives scientists a unique clarity when examining cells in their near-native state at the nanoscale.

By using X-ray absorption spectroscopic methods, the team obtained important information about the valency, geometry, and oxidation state of the gold atom in the complex. These indicate that the antitumor activity of the gold complexes primarily stems from the native cationic species (the [(C^C)Au(P^P)]+ cations). It probably results from interactions between the whole complex and specific biological molecules, whose function is disrupted. This differentiates these drug candidates from other, differently structured gold complexes, which generally trigger cell death through direct coordination of the gold center with biomolecules. These results establish a relationship between the chemical structure and reactivity of a gold complex, its speciation in the cell, and its cytotoxicity.

(3419 characters)

About the Author

Dr. Benoît Bertrand is a CNRS junior researcher at the Institut Parisien de Chimie Moléculaire at Sorbonne Université. His research interest is the development of new organometallic gold complexes and the study of their anticancer properties with a particular focus on the intracellular reactivity of the complexes.

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Journal

Angewandte Chemie International Edition

DOI

10.1002/anie.202422763 

Method of Research

Experimental study

Subject of Research

Cells

Article Title

Stability and Mitochondrial Localization of a Highly Cytotoxic Organogold(III) Complex with Diphosphine Ancillary Ligand in Lung Cancer Cells

Article Publication Date

14-Apr-2025