From Far West to East: Joining the Molecular Architecture of Imidazole-like Ligands in HO-1 Complexes

HO-1 overexpression has been reported in several cases/types of human malignancies. Unfortunately, poor clinical outcomes are reported in most of these cases, and the inhibition of HO-1 is considered a valuable and proven anticancer approach. To identify novel hit compounds suitable as HO-1 inhibitors, we report here a fragment-based approach where ligand joining experiments were used. The two most important parts of the classical structure of the HO-1 inhibitors were used as a starting point, and 1000 novel compounds were generated and then virtually evaluated by structure and ligand-based approaches. The joining experiments led us to a novel series of indole-based compounds. A synthetic pathway for eight selected molecules was designed, and the compounds were synthesized. The biological activity revealed that some molecules reach the micromolar activity, whereas molecule 4d inhibits the HO-1 with an IC50 of 1.03 μM. This study suggested that our joining approach was successful, and a novel hit compound was generated. These results are ongoing for further development.

Structure, NeutroStructure, and AntiStructure in Science

In any science, a classical Theorem, defined on a given space, is a statement that is 100% true (i.e. true for all elements of the space). To prove that a classical theorem is false, it is sufficient to get a single counter-example where the statement is false. Therefore, the classical sciences do not leave room for partial truth of a theorem (or a statement). But, in our world and in our everyday life, we have many more examples of statements that are only partially true, than statements that are totally true. The NeutroTheorem and AntiTheorem are generalizations and alternatives of the classical Theorem in any science. More general, by the process of NeutroSophication, we have extended any classical Structure, in no matter what field of knowledge, to some NeutroStructure, and by the process of AntiSophication to some AntiStructure

Gramatica Critică Sau Critica Gramaticii?

Gramatica critică a limbii române (The Critical Grammar of the Romanian Language), authored by Ștefan Găitănaru, was published in 2018, at the University of Pitești Publishing House. The launch of this book took place during the National Conference on Adaptation, Conservation and Rejection in the Evolution of the Romanian Cultural/ Linguistic/ Literary Phenomenon, held at the Faculty of Letters in Sibiu, on May 24, 2019. The purpose of the book, mentioned by the author in the Preface, is to update the grammar research, emphasizing the normative aspect. Thus, we witness a descriptive-normative grammar, with a classical structure: part I - Morphology and part II - Syntax, each section comprising the description, analysis and interpretation of specific components. This Critical Grammar brings to the surface controversial aspects regarding the grammatical structure of the Romanian language, with pertinent observations and recommendations, with solid arguments, for or against, from case to case.

Iron Oxide/Phosphatic Materials Composites with Potential Applications in Environmental Protection

Currently, hydroxyapatite is probably the most researched material, due to its multiple applications in medical, environmental, or cultural heritage, when the classical structure is modified and calcium is displaced partially or totally with different metals. By changing the classical structure of the hydroxyapatite, new morphologies can be obtained, thus allowing final applications different from those of the initial hydroxyapatite material. However, their properties should be tuned for the desired application. In this context, the present paper describes the synthesis and characterization (through energy-dispersive X-ray fluorescence, X-ray diffraction, FTIR, thermal analysis, and transmission electron microscopy) of iron oxide/manganese-containing phosphatic phase composite materials, developed in order to obtain the enhancement of final environmental applications (photodegradation of dyes, adsorption of organic compounds). The composite material was tested for photocatalytic properties, after embedding in hydrosoluble film-forming materials. Photocatalytic coatings show different activity during the photodecomposition of Methylene Blue, used as a model of a contaminant. The photocatalytic activities of the materials were discussed in relationship with both the phosphatic materials and the magnetic components. Finally, other environmental applications were studied for the developed materials (adsorption of non-steroidal anti-inflammatory drugs—paracetamol and ibuprofen), revealing an enhancement of the adsorption capacity of the phosphatic material upon addition of the magnetic phase.

Planck’s Derivation of E=hν

Planck was unwilling to accept Boltzmann’s statistical interpretation of the second law. He therefore needed to find a way to show how irreversible processes could result from continuous matter. Planck chose the physics of black body radiation as a battleground. After discovering his radiation law in October 1900, he sought a deeper theoretical interpretation for it. Now thermodynamics is not the most obvious place to look for evidence of the quantum nature of radiation and, in an ‘act of desperation’, Planck had to torture the theory in a way that would eventually allow this conclusion to emerge from an entirely classical structure. Planck’s derivation heralded the very beginning of the quantum revolution, but only in promise, not in deed. The revolution began in earnest in 1905 with the help of Albert Einstein.

Strong and Confined Acid Catalysts Impart Stereocontrol onto the Non-Classical 2-Norbornyl Cation

In 1949, S. Winstein and D. Trifan proposed that the 2-norbornyl cation adopts a bridged, non-classical structure with a 3-center, 2-electron unit much like the bonding in diborane. While some embraced this proposal, others firmly refuted it, giving rise to the vituperative 2-norbornyl cation controversy. After 60 years of debate, the long-sought crystallographic proof was eventually collected in 2013. Several decades after the first non-classical formulation, we became interested in imparting stereocontrol over the 2-norbornyl cation, a positively charged, simple hydrocarbon that, due to its structural features, offers a major challenge to asymmetric catalysis. Our investigation began by reversing the original experiment by Winstein. Specifically, we found that IDPi catalysts are competent chiral acids for carrying out a diastereo- and enantioselective C-C bond forming reaction between racemic <i>exo</i>- and <i>endo</i>-norbornyl trichloroacetimidates and 1,3,5-trimethoxybenzene to exclusively deliver the <i>exo</i>-product with excellent enantioselectivities. We also found that several structurally-different substrates can be converted to the same product with good to excellent enantioselectivities, pointing to the existence of a common cationic intermediate. Mechanistic and kinetic studies were conducted to elucidate relevant aspects of the reaction.

Strong and Confined Acid Catalysts Impart Stereocontrol onto the Non-Classical 2-Norbornyl Cation

In 1949, S. Winstein and D. Trifan proposed that the 2-norbornyl cation adopts a bridged, non-classical structure with a 3-center, 2-electron unit much like the bonding in diborane. While some embraced this proposal, others firmly refuted it, giving rise to the vituperative 2-norbornyl cation controversy. After 60 years of debate, the long-sought crystallographic proof was eventually collected in 2013. Several decades after the first non-classical formulation, we became interested in imparting stereocontrol over the 2-norbornyl cation, a positively charged, simple hydrocarbon that, due to its structural features, offers a major challenge to asymmetric catalysis. Our investigation began by reversing the original experiment by Winstein. Specifically, we found that IDPi catalysts are competent chiral acids for carrying out a diastereo- and enantioselective C-C bond forming reaction between racemic <i>exo</i>- and <i>endo</i>-norbornyl trichloroacetimidates and 1,3,5-trimethoxybenzene to exclusively deliver the <i>exo</i>-product with excellent enantioselectivities. We also found that several structurally-different substrates can be converted to the same product with good to excellent enantioselectivities, pointing to the existence of a common cationic intermediate. Mechanistic and kinetic studies were conducted to elucidate relevant aspects of the reaction.