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Biochemistry

A New Therapy for Heart Attacks: Injecting a Protein-Like Polymer to Promote Healing

Researchers have developed a new therapy that can be injected intravenously right after a heart attack to promote healing and prevent heart failure. The therapy both prompts the immune system to encourage tissue repair and promotes survival of heart muscle cells after a heart attack. Researchers tested the therapy in rats and showed that it is effective up to five weeks after injection.

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The medical community has made significant strides in understanding the complexities of the human body. Researchers at the University of California San Diego and Northwestern University have developed an innovative therapy that can be injected intravenously after a heart attack to encourage tissue repair and prevent heart failure. This groundbreaking approach aims to intervene early, potentially keeping patients from ultimately going into heart failure.

The research team, led by bioengineers and chemists, published their findings in the April 25 issue of Advanced Materials. They demonstrated that this therapy is effective up to five weeks after injection in rat models. The protein-like polymer (PLP) platform mimics a key protein called Nrf2, which cells rely on to resist degradation brought on by inflammation.

After a heart attack, the interaction between two proteins – Nrf2 and KEAP1 – must be blocked for tissues to heal properly. When KEAP1 binds with Nrf2, it degrades the latter, hindering tissue repair. By injecting the PLP platform intravenously, researchers can prevent this degradation process, allowing cells to function normally.

The rat models injected with the PLP platform showed better cardiac function and significantly more healing in their heart muscle tissue compared to those receiving a saline solution. Other tests also revealed that genes promoting tissue healing were expressed more in the treated animals.

Researchers describe this study as a proof of concept, aiming to optimize the design and dosage before moving on to larger mammal trials. This therapy has the potential for broader applications beyond heart attacks, addressing diseases such as macular degeneration, multiple sclerosis, and kidney disease.

The innovative PLP platform could transform the treatment landscape by providing an effective solution for a critical clinical need – preventing heart failure after a heart attack. This breakthrough demonstrates the power of interdisciplinary research in tackling complex medical challenges.

Sources:

* Gianneschi, N., et al. (2023). A protein-like polymer platform to intervene with KEAP1-Nrf2 interactions promotes cardiac repair and function in a rat model of myocardial infarction. Advanced Materials, 35(14), e2205550.
* National Institutes of Health National Heart, Lung, and Blood Institute (NHLBI) research grants 2R01HL139001, R00 CA248715.

Biochemistry

Shape-Shifting Catalysts: Revolutionizing Green Chemistry with a Single Atom

A team in Milan has developed a first-of-its-kind single-atom catalyst that acts like a molecular switch, enabling cleaner, more adaptable chemical reactions. Stable, recyclable, and eco-friendly, it marks a major step toward programmable sustainable chemistry.

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The scientific community has witnessed a groundbreaking development in sustainable chemistry with the creation of a shape-shifting single-atom catalyst at the Politecnico di Milano. This innovative material has demonstrated the capability to selectively adapt its chemical activity, paving the way for more efficient and programmable industrial processes.

Published in the Journal of the American Chemical Society, one of the world’s most esteemed scientific journals in chemistry, this study marks a significant breakthrough in the field of single-atom catalysts. For the first time, scientists have successfully designed a material that can change its catalytic function depending on the chemical environment, much like a ‘molecular switch.’ This allows complex reactions to be performed more cleanly and efficiently, using less energy than conventional processes.

The research focuses on a palladium-based catalyst in atomic form encapsulated in a specially designed organic structure. This unique setup enables the material to ‘switch’ between two essential reactions in organic chemistry – bioreaction and carbon-carbon coupling – simply by varying the reaction conditions. The team has successfully demonstrated this phenomenon, showcasing the potential for more intelligent, selective, and sustainable chemical transformations.

Lead researcher Gianvito Vilé, lecturer at the Politecnico di Milano’s ‘Giulio Natta’ Department of Chemistry, Materials and Chemical Engineering, emphasizes the significance of their discovery: “We have created a system that can modulate catalytic reactivity in a controlled manner, paving the way for more intelligent, selective, and sustainable chemical transformations.”

The new catalyst stands out not only for its reaction flexibility but also for its stability, recyclability, and reduced environmental impact. ‘Green’ analyses conducted by the team reveal a substantial decrease in waste and hazardous reagents, making it an exemplary model for sustainable chemistry.

This study is the result of an international collaboration with esteemed institutions from around the world, including the University of Milan-Bicocca, the University of Ostrava (Czech Republic), the University of Graz (Austria), and Kunsan National University (South Korea). The joint efforts of these researchers have led to a groundbreaking achievement that has far-reaching implications for the field of green chemistry.

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Biochemistry

Scientists Finally Tame the Impossible: A Stable 48-Atom Carbon Ring is Achieved

Researchers have synthesized a stable cyclo[48]carbon, a unique 48-carbon ring that can be studied in solution at room temperature, a feat never achieved before.

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The discovery of a new type of molecular carbon allotrope, known as cyclocarbon, has been a long-standing challenge for chemists. A team of researchers from Oxford University’s Department of Chemistry, led by Dr Yueze Gao and senior author Professor Harry Andersen, have successfully synthesized a stable 48-atom carbon ring in solution at room temperature. This achievement marks a significant breakthrough in the field, as previous attempts to study cyclocarbons were limited to the gas phase or extremely low temperatures (4 to 10 K).

The researchers employed a unique approach by synthesizing a cyclocarbon catenane, where the C48 ring is threaded through three other macrocycles. This design increases the stability of the molecule, preventing access to the sensitive cyclocarbon core. The team developed mild reaction conditions for the unmasking step in the synthesis process, which allowed them to achieve a stable cyclocarbon in solution at 20°C.

The cyclocarbon catenane was characterized using various spectroscopic techniques, including mass spectrometry, NMR, UV-visible, and Raman spectroscopy. The observation of a single intense 13C NMR resonance for all 48 sp1 carbon atoms provides strong evidence for the cyclocarbon catenane structure.

Lead author Dr Yueze Gao stated that achieving stable cyclocarbons in a vial at ambient conditions is a fundamental step, making it easier to study their reactivity and properties under normal laboratory conditions. Senior author Professor Harry Andersen added that this achievement marks the culmination of a long endeavor, with the original grant proposal written in 2016 based on preliminary results from 2012-2015.

The study also involved researchers from the University of Manchester, the University of Bristol, and the Central Laser Facility, Rutherford Appleton Laboratory. This collaborative effort demonstrates the power of interdisciplinary research in advancing our understanding of complex molecular systems.

This achievement has significant implications for future studies on cyclocarbons and their potential applications in various fields. The researchers’ innovative approach to synthesizing stable cyclocarbons at room temperature opens up new possibilities for exploring the properties and reactivity of these intriguing molecules.

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Biochemistry

“Revolutionizing Medicine: A 100x Faster Path to Life-Saving Drugs with Metal Carbenes”

Using a clever combo of iron and radical chemistry, scientists have unlocked a safer, faster way to create carbenes molecular powerhouses key to modern medicine and materials. It s 100x more efficient than previous methods.

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Chemists have made a groundbreaking breakthrough in developing a novel method to generate highly useful chemical building blocks by harnessing metal carbenes. This achievement is expected to revolutionize the synthesis of life-saving drugs and materials development.

Typically used in chemical reactions essential for drug synthesis, carbenes are short-lived, highly reactive carbon atoms. However, creating these carbenes has been a challenging task due to limited methods and hazardous procedures.

Researchers at The Ohio State University have now developed an approach that makes producing metal carbenes much easier and safer. According to David Nagib, co-author of the study and distinguished professor in arts and sciences, “Our goal all along was to determine if we could come up with new methods of accessing carbenes that others hadn’t found before.”

The team’s innovative method uses iron as a metal catalyst and combines it with chlorine-based molecules that easily generate free radicals. This combination works to form the carbene of their choice, including many that had never been made before.

These three-sided molecular fragments, known as cyclopropanes, are vital to the synthesis of medicines and agrichemicals due to their small size and unusual energy. The researchers’ work was inspired by looking for the best ways to create these shape, which is one of the most common found in medicines.

“Our lab is obsessed with trying to get the best methods for making cyclopropanes out there as soon as possible,” said Nagib. “We have the eye on the prize of inventing better tools to make better medicines, and along the way, we’ve solved a huge problem in the carbene world.”

The study was recently published in Science, and the team’s discovery is expected to become extremely impactful. By accessing a new way of creating and classifying carbenes, scientists can simplify and improve the current wasteful, multistep process of producing them.

For consumers, this method suggests that future drugs developed by this technology may be cheaper, more potent, faster-acting, and longer-lasting. The work could prevent shortages of important medicines like antibiotics and antidepressants, as well as drugs that treat heart disease, COVID, and HIV infections, said Nagib.

Additionally, the team would like to ensure that their transformational organic chemistry tool is accessible to both big and small research labs and drug manufacturers around the world. One way to guarantee this is by continuing to improve the current technique, said Nagib.

“Our team at Ohio State came together in the coolest, most collaborative way to develop this tool,” he said. “So we’re going to continue racing to show how many different types of catalysts it could work on and make all kinds of challenging and valuable molecules.”

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