Tag Archives: #compound

Novel Compound Reveals Fundamental Properties of Smallest Carbon Nanotubes (Physics)

Chemical rings of carbon and hydrogen atoms curve to form relatively stable structures capable of conducting electricity and more — but how do these curved systems change when new components are introduced? Researchers based in Japan found that, with just a few sub-atomic additions, the properties can pivot to vary system states and behaviors, as demonstrated through a new synthesized chemical compound.

The results were published on April 26 in the Journal of the American Chemical Society.

“In the past decade, open-shell molecules have attracted considerable attention not only in the field of reactive intermediates, but also in materials science,” said paper author Manabu Abe, professor in the Graduate School of Advanced Science and Engineering, Hiroshima University.

Open-shell molecules can gain or lose molecules, meaning they can adjust to bond with other chemicals. In carbon nanotubes, for example, rings of carbon and hydrogen atoms strongly bond to one another. The more rings added, however, the more the properties of the tube can change. Known as curved paraphenylenes, or CPPs, Abe and his team investigated how the CPP might change if the open-shell molecules were exposed to systems with molecular orbits containing two electrons in various states, in addition to the carbon and hydrogen atoms.

The process of introducing these diradical systems to the CPPs resulted in a novel type of azoalkane, or compound of nitrogen and a group of weakly bonded hydrogen and carbon atoms. This azoalkane formed with six CPPs and degenerated into six CPPs with diradicals.

“We investigated to understand the effects of the curvature and system size on the particle interactions, the different states and their unique characteristics,” Abe said.

The researchers found that the CPPs with embedded diradicals had varying states and properties, such as the intrinsic description of a particle known as spin, depending on how many CPPs resulted in the final system. Spin, the angular momentum of a particle, can contribute to or hinder a system’s stability based on how the energy is balance. For example, in a singlet state, a system remains stable even with unbonded electrons, because their spins are opposite. Triplet states can remain stable, as well, since their unbonded electrons can spin in parallel.

“The ground-state spin multiplicity is largely dependent on the ring size,” Abe said, referring to the potential orientations spin can take, which can indicate the stability of a system. “The singlet ground state was favored for smaller CPP derivatives.”

The smaller singlet states — diradical CPPs with smaller energy ranges between orbital shells — also demonstrated a desired characteristic for carbon nanotubes: aromaticity, or more stable alignment in a single plane. Since the carbon-hydrogen rings bond with unusual angles to form the tubes, they can be forced out of alignment and result in system instability. The more rings added to a system, the more strained the system becomes. For the smaller singlet state systems, the rings align in one plane, resulting in more stability.

Next, the researchers plan to further investigate this in-plane aromaticity, with the aim of creating the largest possible structure with strong bonds that still exhibits this stable property.

Co-authors include Ivana Antol, Laboratory for Physical Organic Chemistry, Division of Organic Chemistry and Biochemistry, Ruder Bošvoíc Institute; Shigeru Yamago and Eiichi Kayahara, Institute for Chemical Research, Kyoto University; and Yuki Miyazawa, Zhe Wang, Misaki Matsumoto and Sayaka Hatano, Department of Chemistry, Graduate School of Advanced Science and Engineering, Hiroshima University.

Japan Society for the Promotion of Science, Japan Science and Technology Agency and International Collaborative Research Program of the Institute for Chemical Research at Kyoto University funded this work.

Featured image: The effects of the curvature contributes to their ground spin state. © Manabu Abe, Hiroshima University


Reference: Yuki Miyazawa, Zhe Wang, Misaki Matsumoto, Sayaka Hatano, Ivana Antol, Eiichi Kayahara, Shigeru Yamago, and Manabu Abe, “1,3-Diradicals Embedded in Curved Paraphenylene Units: Singlet versus Triplet State and In-Plane Aromaticity”, J. Am. Chem. Soc. 2021, 143, 19, 7426–7439.
https://doi.org/10.1021/jacs.1c01329


Provided by Hiroshima University

The Compound That Makes Chili Peppers Spicy also Boosts Perovskite Solar Cell Performance ( Material Science)

Scientists in China and Sweden have determined that a pinch of capsaicin, the chemical compound that gives chili peppers their spicy sting, may be a secret ingredient for more stable and efficient perovskite solar cells. The research, published January 13 in the journal Joule, determined that sprinkling capsaicin into the precursor of methylammonium lead triiodide (MAPbI3) perovskite during the manufacturing process led to a greater abundance of electrons (instead of empty placeholders) to conduct current at the semiconductor’s surface. The addition resulted in polycrystalline MAPbI3 solar cells with the most efficient charge transport to date.

This photo shows perovskite solar cells containing capsaicin. © Jin Yang

“In the future, green and sustainable forest-based biomaterial additive technology will be a clear trend in non-toxic lead-free perovskite materials,” says Qinye Bao, a senior author of the study from East China Normal University. “We hope this will eventually yield a fully green perovskite solar cell for a clean energy source.”

While metal halide perovskite semiconductors represent a promising component for state-of-the-art solar cell technologies, they are plagued by nonradiative recombination, an undesirable electron-level process that reduces efficiency and exacerbates heat losses. Bao and colleagues sought out a natural, forest-based, inexpensive additive to overcome this limitation and enhance solar cell performance.

“Considering the electric, chemical, optical, and stable properties of capsaicin, we preliminarily found that it would be a promising candidate,” says Bao.

To test capsaicin’s capabilities, Bao and colleagues added 0.1 wt% of the compound (the optimal determined concentration) into a MAPbI3 perovskite precursor, which they used to fabricate solar cells. Next, the researchers performed a series of techniques, including ultraviolet photoelectron spectroscopy, X-ray photoelectron spectroscopy, and time-resolved photoluminescence to determine how the capsaicin additive affected the solar cells’ properties. They found that while control devices showed a power conversion efficiency of only 19.1%, devices containing capsaicin had an efficiency of 21.88% – nearly as high as the record 21.93% efficiency of single-crystal MAPbI3 devices. The enhanced solar cells also showed improved stability, maintaining more than 90% of their initial efficiency after 800 hours of storage in ambient air.

Bao and colleagues also determined that capsaicin greatly reduced the perovskite film’s defect density, increasing electron density by an order of magnitude and boosting charge transport. Additionally, they observed a smaller leakage current in solar cells containing the chili pepper compound, suggesting it successfully suppressed nonradiative recombination.

Capsaicin enabled these improvements by transforming the perovskite material’s surface energetics, creating an interface between p-type semiconductor layers, which contain more electron-deficient “holes” than electrons, and n-type semiconductor layers, which contain more electrons than “holes.” This interface promotes charge transport and suppresses the loss of efficiency observed in traditional perovskite semiconductors.

While capsaicin may provide a low-cost, widely available additive for the future development of scaled-up, highly efficient perovskite solar cells, Bao and colleagues note that further research is required to investigate the compound’s effect on non-toxic, lead-free perovskites such as inorganic perovskite and double perovskite. Additionally, the material’s stability must be further honed before it will be ready for commercial applications.

“We will further focus on the relationship between chemical structures of natural forest-based biomaterial additives, their interaction with photoactive materials, and the corresponding photovoltaic performance,” says Bao. “We hope to generate new knowledge of great value to further increase the power conversion efficiency and stability of perovskite solar cells.”

This work was supported by the National Science Foundation of China, the Fundamental Research Funds for the Central Universities, Shanghai Rising-Star, East China Normal University Multifunctional Platform for Innovation, the Swedish Government Strategic Research Area in Materials Science on Functional Materials at Linköping University, the National Key Research and Development Program of China, and the National Natural Science Foundation of China.

Reference: Joule, Hao and Xiong et al.: “Direct observation on p- to n-type transformation of perovskite surface region during defect passivation driving high photovoltaic efficiency” https://www.cell.com/joule/fulltext/S2542-4351(20)30608-5

Provided by Cell Press

Unravelling The Multifaceted Mechanisms Of Cancer Cell Death By Mutant p53 Targeting Compound APR-246 (Medicine)

Sophia Ceder and Klas Wiman and their colleagues at Department of Oncology-Pathology have together with researchers from Peter MacCallum Cancer Center, University of Melbourne, University of Cambridge and Aprea Therapeutics published a study in EMBO Molecular Medicine that provides novel understanding on the mechanisms of mutant p53 targeting compound APR-246.

Around half of all tumors carry mutations in the tumor suppressor gene TP53 which is often associated with poor prognosis. The molecule APR-246 (Eprenetapopt) was discovered by Wiman and colleagues around 20 years ago (Bykov et al 2002) and is today the clinically most advanced compound that targets mutant p53. Currently, APR-246 is undergoing a Phase III clinical trial in mutant TP53 myelodysplastic syndrome (MDS) and several Phase II studies in various indications. Earlier this year APR-246 received FDA Breakthrough Therapy Designation for the combination with Azacitidine for the treatment of mutant TP53 MDS and recently also received FDA Fast Track Designation in mutant TP53 acute myeloid leukemia (AML).

The study investigates the multifaceted mechanisms of action of APR-246 to improve therapeutic efficacy and increase our understanding of APR-246 pharmacodynamics in cancer cells. APR-246 targets mutant p53 and also induces oxidative stress by binding glutathione (GSH) or inhibiting antioxidant enzymes, both major mechanisms of APR-246-mediated cancer cell death. MQ, the active conversion product of APR‐246, forms reversible conjugates with the major antioxidant GSH. The study shows that this complex (GSH bound-MQ) can be exported through the multidrug resistance‐associated protein 1 (MRP1) efflux pump and that blocking MRP1 traps MQ inside cancer cells. This forms an intracellular drug reservoir that may enhance targeting of mutant p53 and disrupt the intracellular redox balance. Blocking MRP1 in combination with APR-246 expands the therapeutic window and leads to pronounced synergistic cancer cell death in vitro in cancer cell lines, ex vivo in patient-derived organoids and in vivo in mice with tumor xenografts.

In conclusion, the study explains the dynamics of APR‐246 and MQ in cancer cells and indicates that MRP1 can play a key role in the sensitivity to APR‐246. Altogether our findings suggest that combination treatment with APR‐246 and drugs that target the redox balance may allow more efficient cancer therapy.

Reference: Sophia Ceder et al. A thiol‐bound drug reservoir enhances APR‐246‐induced mutant p53 tumor cell death, EMBO Molecular Medicine (2020). DOI: 10.15252/emmm.201910852

Provided by Karolinska Institutet

New Synthetic Molecule Can Kill The Flu Virus (Medicine)

EPFL scientists have developed a synthetic molecule capable of killing the virus that causes influenza. They hope their discovery will lead to an effective drug treatment.

Influenza is one of the most widespread viral diseases and constitutes a major public health problem. For some, it means spending a week in bed; for others, it could lead to hospitalization or, in the most severe cases, death. Scientists at EPFL’s Supramolecular Nano-Materials and Interfaces Laboratory (SuNMIL) within the School of Engineering, working in association with the team headed by Caroline Tapparel, a professor at the University of Geneva’s Department of Microbiology and Molecular Medicine, have synthesized a compound that can kill the virus that causes influenza. Their discovery paves the way to effective drug therapies against the seasonal disease. The research has been published in Advanced Science.

Symptoms appearing too late

“With the flu virus, the risk of a pandemic is high,” says Francesco Stellacci, the EPFL professor who heads SuNMIL. “Scientists have to update the vaccine every year because the strain mutates, and sometimes the vaccine turns out to be less effective. So it would be good to also have antivirals that could limit the effects of large-scale infection.” Antiviral drugs already exist, and Tamiflu is the most well-known. But it has one major drawback – it has to be taken within 36 hours of infection or it loses its efficacy completely. And with influenza, symptoms generally start appearing 24 hours after infection. “By the time patients seek medical treatment, it’s often too late for Tamiflu,” Stellacci. “In addition, for antivirals to really work, they have to be virucidal – that is, they have to irreversibly inhibit viral infectivity. But today that’s not the case.”

Effective and non-toxic

Developing a flu drug is no mean feat – not only does the virus mutate, but the drug has to be innocuous to the human body. “The chances of survival with influenza are high, so any drug has to have little or no side effects. Otherwise it wouldn’t be worth taking,” notes Stellacci.

Francesco Stellacci in his lab © 2020 EPFL

The flu virus attaches to a cell membrane in order to infect a human body; it then detaches and goes on to infect other cells. Existing antiviral drugs work by attacking the virus inside a host cell and temporarily blocking viral replication. The EPFL scientists took a new approach with their antiviral compound in order to make it both effective against influenza and non-toxic. They developed a modified sugar molecule that mimics a cell membrane, tricking the flu virus into attaching to it. “Once the virus is attached, our molecule exerts pressure locally and destroys it. And this mechanism is irreversible,” says Stellacci.

Because this process occurs outside the body’s cells, this synthetic compound demonstrates constant efficacy during the first 24 hours after infection, based on tests conducted on mice. This suggests that in humans, the compound’s efficacy could last beyond 36 hours. According to Stellacci: “The efficacy of oseltamivir” – the active ingredient in Tamiflu – “in mice is almost completely lost after 24 hours.” What’s more, the EPFL-developed compound could be used to create broad-spectrum antivirals – that is, drugs that act against many different kinds of flu viruses. This research focuses mainly on seasonal influenza and does not address efforts to develop a treatment for Covid-19.

Funding: This research was made possible thanks to funding from the Warner Siemens Foundation.

References: Kocabiyik, O., Cagno, V., Silva, P. J., Zhu, Y., Sedano, L., Bhide, Y., Mettier, J., Medaglia, C., Da, B., Constant, S., Huang, S., Kaiser, L., Hinrichs, W. L. J., Huckeriede, A., Le, R., Tapparel, C., Stellacci, F., Non‐Toxic Virucidal Macromolecules Show High Efficacy Against Influenza Virus Ex Vivo and In Vivo. Adv. Sci. 2020, 2001012. https://onlinelibrary.wiley.com/doi/10.1002/advs.202001012 https://doi.org/10.1002/advs.202001012

Provided by EPFL

Cord Blood DNA Can Hold Clues For Early ASD Diagnosis And Intervention (Medicine)

A new study led by UC Davis MIND Institute researchers found a distinct DNA methylation signature in the cord blood of newborns who were eventually diagnosed with autism spectrum disorder (ASD). This signature mark spanned DNA regions and genes linked to early fetal neurodevelopment. The findings may hold clues for early diagnosis and intervention.

“We found evidence that a DNA methylation signature of ASD exists in cord blood with specific regions consistently differentially methylated,” said Janine LaSalle, lead author on the study and professor of microbiology and immunology at UC Davis.

The study published Oct. 14 in Genome Medicine also identified sex-specific epigenomic signatures that support the developmental and sex-biased roots of ASD.

The U.S. Centers for Disease Control and Prevention (CDC) estimates that one in 54 children are diagnosed with ASD, a complex neurological condition linked to genetic and environmental factors. It is much more prevalent in males than females.

The role of the epigenome in DNA functioning

The epigenome is a set of chemical compounds and proteins that tell the DNA what to do. These compounds attach to DNA and modify its function. One such compound is CH3 (known as the methyl group) that could lead to DNA methylation. DNA methylation can change the activity of a DNA segment without changing its sequence. Differentially methylated regions (DMRs) are areas of DNA that have significantly different methylation status.

The epigenome compounds do not change the DNA sequence but affect how cells use the DNA’s instructions. These attachments are sometimes passed on from cell to cell as cells divide. They can also be passed down from one generation to the next. The neonatal epigenome has the potential to reflect past interactions between genetic and environmental factors during early development. They may also influence future health outcomes.

Finding factors in fetal cord blood that might predict autism

The researchers studied the development of 152 children born to mothers enrolled in the MARBLES and EARLI studies. These mothers had at least one older child with autism and were considered at high risk of having another child with ASD. When these children were born, the mothers’ umbilical cord blood samples were preserved for analysis. At 36 months, these children got diagnostic and developmental assessments. Based on these, the researchers grouped the children under “typically developing” (TD) or “with ASD.”

The researchers also analyzed the umbilical cord blood samples taken at birth from the delivering mothers. They performed whole-genome sequencing of these blood samples to identify an epigenomic signature or mark of ASD at birth. They were checking for any patterns of DNA-epigenome binding that could predict future ASD diagnosis.

They split the samples into discovery and replication sets and stratified them by sex. The discovery set included samples from 74 males (39 TD, 35 ASD) and 32 females (17 TD, 15 ASD). The replication set was obtained from 38 males (17 TD, 21 ASD) and eight females (3TD, 5 ASD).

Using the samples in the discovery set, the researchers looked to identify specific regions in the genomes linked to ASD diagnosis. They tested the DNA methylation profiles for DMRs between ASD and TD cord blood samples. They mapped the DMRs to genes and assessed them in gene function, tissue expression, chromosome location and overlap with prior ASD studies. They later compared the results between discovery and replication sets and between males and females.

Cord blood to reveal insights into genes related to ASD

The researchers identified DMRs stratified by sex that discriminated ASD from TD cord blood samples in discovery and replication sets. They found that seven regions in males and 31 in females replicated, and 537 DMR genes in males and 1762 DMR genes in females replicated by gene association. These DMRs identified in cord blood overlapped with binding sites relevant to fetal brain development. They showed brain and embryonic expression and X chromosome location and matched with prior epigenetic studies of ASD.

“Findings from our study provide key insights for early diagnosis and intervention,” LaSalle said. “We were impressed by the ability of cord blood to reveal insights into genes and pathways relevant to the fetal brain.”

The researchers pointed out that these results will require further replication before being used diagnostically. Their study serves as an important proof of principle that the cord blood methylome is informative about future ASD risk.

References: Mordaunt et al. (2020). Cord blood DNA methylome in newborns later diagnosed with autism spectrum disorder reflects early dysregulation of neurodevelopmental and X-linked genes, Genome Medicine, doi: https://doi.org/10.1186/s13073-020-00785-8

Provided by University Of California davis health