Monomeric Form Research Articles

Evaluation of Anti-Alzheimer's Potential of Azo-Stilbene-Thioflavin-T derived Multifunctional Molecules: Synthesis, Metal and Aβ Species Binding and Cholinesterase Activity.

Inhibition of amyloid β (Aβ) aggregation and cholinesterase activity are two major therapeutic targets for Alzheimer's disease (AD). Multifunctional Molecules (MFMs) specifically designed to address other contributing factors, such as metal ion induced abnormalities, oxidative stress, toxic Ab aggregates etc. are very much required. Several multifunctional molecules have been developed using different molecular scaffolds. Reported herein is a new series of four MFMs based on ThT, Azo-stilbene and metal ion chelating pockets. The synthesis, characterization, and metal chelation ability for [Cu(II) and Zn(II)] are presented herein. Furthermore, we explored their multifunctionality w.r.t. to their (i) recognition of Aβ aggregates and monomeric form, (ii) utility in modulating the aggregation pathways of both metal-free and metal-bound amyloid-β, (iii) ex-vivo staining of amyloid plaques in 5xFAD mice brain sections, (iv) ability to scavenge free radicals and (v) ability to inhibit cholinesterase activity. Molecular docking studies were also performed with Aβ peptides and acetylcholinesterase enzyme to understand the observed inhibitory effect on activity. Overall, the studies presented here establish the multifunctional nature of these molecules and qualify them as promising candidates for furthermore investigation in the quest for finding Alzheimer's disease treatment.

MAD2L2 Dimerization Is Not Essential for Mitotic Regulation

MAD2L2 is a small HORMA domain protein that plays a crucial role in DNA repair and mitosis. In both TLS and shieldin, the dimerization of MAD2L2 via its HORMA domain is critical for the stability and function of these complexes. However, in mitosis, the dimerization state of MAD2L2 remains unknown. To assess the importance of MAD2L2’s dimerization during mitosis, we utilized CRISPR/Cas9 to generate MAD2L2 knockout cells, which were subsequently complemented with MAD2L2 species carrying different dimer-disrupting point mutations. We assessed the ability of these MAD2L2 dimer-disrupting mutants to regulate mitosis by evaluating early mitotic events and mitotic fidelity. Our findings indicate that MAD2L2 can function in its monomeric form during mitosis, suggesting that MAD2L2 homodimerization is dispensable for early mitotic regulation. Furthermore, our results suggest that the binding of CDH1 to MAD2L2 is a key regulating factor in mitosis that may actively prevent the formation of MAD2L2 dimers, thereby shifting the cellular balance toward MAD2L2-CDH1 interaction. Thus, the equilibrium between the monomeric and dimeric forms of MAD2L2 is an important cellular factor regulating the MAD2L2-containing complexes.

Enhanced Singlet Oxygen Generation in Aggregates of Naphthalene-Fused BODIPY and Its Application in Photodynamic Therapy.

Several reports are available on aggregation-induced emission and its applications in biomedical imaging and other material sciences. However, enhancement of singlet oxygen generation in nanoaggregates is rarely reported. Here, we report the synthesis of Naph-BODIPY Br2, which absorbs at 661 nm (monomer) with a high molar absorption coefficient. The presence of bromine promotes intersystem crossing, thereby enhancing the singlet oxygen quantum yield (ΦΔ ∼ 0.50 in methanol). In order to increase hydrophilicity, we developed Naph-BODIPY Br2 nanoaggregates (∼100 nm), which demonstrated aggregation-induced properties and exhibited a bathochromic shift with an absorption maximum at 757 nm. The bathochromic shift in the UV-vis spectra due to aggregation is corroborated by TD-DFT analysis. The computational data also confirm the presence of a low-lying triplet state, which enhances the generation of singlet oxygen, making it effective for photodynamic therapy. These aggregates showed excellent singlet oxygen generation in aqueous media, compared to their monomeric form and standard methylene blue. Their hydrophilic nature and high singlet oxygen generation enabled significant phototoxicity against human carcinoma cells with IC50 values of 4.06 ± 0.01 and 4.09 ± 0.1 μM, respectively, for MCF-7 and A549 cells upon 5 min exposure to light. Moreover, their phototoxicity further increases with an increasing exposure time of light for both cell lines. Notably, Naph-BODIPY Br2 nanoaggregates exhibited nearly zero dark cell toxicity and effectively induced apoptosis in cancer cells upon light activation, highlighting their potential as powerful photosensitizers for photodynamic cancer therapy.

SYNBIP 2.0: epitopes mapping, sequence expansion and scaffolds discovery for synthetic binding protein innovation.

Synthetic binding proteins (SBPs) represent a pivotal class of artificially engineered proteins, meticulously crafted to exhibit targeted binding properties and specific functions. Here, the SYNBIP database, a comprehensive resource for SBPs, has been significantly updated. These enhancements include (i) featuring 3D structures of 899 SBP-target complexes to illustrate the binding epitopes of SBPs, (ii) using the structures of SBPs in the monomer or complex forms with target proteins, their sequence space has been expanded five times to 12 025 by integrating a structure-based protein generation framework and a protein property prediction tool, (iii) offering detailed information on 78 473 newly identified SBP-like scaffolds from the RCSB Protein Data Bank, and an additional 16401555 ones from the AlphaFold Protein Structure Database, and (iv) the database is regularly updated, incorporating 153 new SBPs. Furthermore, the structural models of all SBPs have been enhanced through the application of the AlphaFold2, with their clinical statuses concurrently refreshed. Additionally, the design methods employed for each SBP are now prominently featured in the database. In sum, SYNBIP 2.0 is designed to provide researchers with essential SBP data, facilitating their innovation in research, diagnosis and therapy. SYNBIP 2.0 is now freely accessible at https://idrblab.org/synbip/.

Global profiling of protein complex dynamics with an experimental library of protein interaction markers.

Methods to systematically monitor protein complex dynamics are needed. We introduce serial ultrafiltration combined with limited proteolysis-coupled mass spectrometry (FLiP-MS), a structural proteomics workflow that generates a library of peptide markers specific to changes in PPIs by probing differences in protease susceptibility between complex-bound and monomeric forms of proteins. The library includes markers mapping to protein-binding interfaces and markers reporting on structural changes that accompany PPI changes. Integrating the marker library with LiP-MS data allows for global profiling of protein-protein interactions (PPIs) from unfractionated lysates. We apply FLiP-MS to Saccharomyces cerevisiae and probe changes in protein complex dynamics after DNA replication stress, identifying links between Spt-Ada-Gcn5 acetyltransferase activity and the assembly state of several complexes. FLiP-MS enables protein complex dynamics to be probed on any perturbation, proteome-wide, at high throughput, with peptide-level structural resolution and informing on occupancy of binding interfaces, thus providing both global and molecular views of a system under study.

Comparative Bindings of Glycosaminoglycans with CXCL8 Monomer and Dimer: Insights from Conformational Dynamics and Kinetics of Hydrogen Bonds.

GAGs bind to both the monomeric and dimeric forms of CXCL8, helping to form a concentration gradient of the chemokine that facilitates the recruitment of neutrophils to an injury site and supports other biological functions. In this study, atomistic molecular dynamics simulations were conducted to investigate the binding behavior of two hexameric GAGs sulfated at two different positions, chondroitin sulfate (CS) and heparan sulfate (HS), with the monomer (SIL8) and dimer (DIL8) forms of the CXCL8 protein. The results support that the conformational diversity of CS and HS appeared to be more when binding with monomer SIL8 than dimer DIL8. CS gained more configurational entropy from glycosidic linkage flexibility when bound to SIL8 than DIL8, with a higher energy barrier, whereas HS exhibited a lower energy barrier for configurational entropy when bound to SIL8 and DIL8. The monomer SIL8 exhibited more favorable and preferential binding with GAGs compared to DIL8. Formation of hydrogen bonds with the basic amino acids of SIL8 and GAG was more rigid and required higher activation energy to break than the other identified hydrogen bondings. Water molecules involved in hydrogen bonding with GAGs, excluding those with basic amino acids of DIL8, showed longer lifetimes and slower relaxation compared to SIL8. This suggests that water-mediated interactions also favor binding of DIL8 with GAGs. Despite having more basic amino acids, DIL8 did not display stronger binding than SIL8, indicating the significant role of basic residues in stabilizing the GAG-protein interactions in the monomers. The reason could be that the greater number of nonbasic amino acids in dimeric CXCL8 stabilizes the complex by forming water-mediated hydrogen bonds, reducing the conformational preferences for binding with GAGs. In contrast, the monomeric form of CXCL8 exhibits a higher conformational preference for protein-GAG interactions.

Liposomes in Anticancer Strategies

Chemotherapy drugs are not fully selective for cancer cells - they can also destroy healthy cells. Recent advances in nanotechnology have offered hope to overcome this problem. Liposome carriers are widely studied for their use to deliver drugs and genes inside cancer cells. Gemini quaternary ammonium salts (QAS) show great application potential among lipid carriers. Structures made of Gemini surfactants are characterized by a lower critical micelle concentration (CMC) and higher effectiveness in lowering the surface tension compared to monomeric forms of this type of compound. Encapsulation of a drug or genetic material is one of the critical steps in the formation of liposomal carriers. This efficient process allows one to minimize the number of necessary liposomes capable of delivering a certain amount of active substance. Delivery of a liposome to a solid tumor depends on the physiological factors of the tumor - vascularity, lymphatic drainage, interstitial fluid pressure – and on the physicochemical properties of the carrier. Many nanoparticles for targeted drug delivery have been tested in animal studies but have not achieved satisfactory clinical success. Promising preclinical research results are not always reflected in the treatment of patients. Therefore, understanding the relationships governing the transport of the drug and the carrier to the cancer cell seems to be a key challenge in modern nanotechnology.

Carbon Dioxide Capture and Sequestration for Production of Synthetic Materials

The processes of carbon dioxide sequestration at obtaining various inorganic carbonate materials, including with the use of biotechnologies, and formation of organic polymers and monomers for them from CO2 are considered. It is revealed that in the case of inorganic materials the use of slags and sludges containing a large amount of metal oxides from various industries looks the most appropriate, and in the case of materials based on organic polymers the technologies based on polycarbonates, as well as polycarbonate-containing polyols and phosgene-free isocyanates for polyurethanes are preferable. New promising methods under active development but not yet industrially applied, such as electrochemical reduction of carbon dioxide and its condensation with butadiene, are analyzed.

In silico Analysis and Characterization of the F5H Gene Family in Sorghum bicolor and Its Role in Lignin Production

Ferulate 5-hydroxylase (F5H), a cytochrome P450-dependent monooxygenase, catalyzes the hydroxylation of coniferaldehyde, a crucial step in the formation of syringyl lignin monomer (S). However, evolutionary divergence, expression patterns under abiotic stress conditions (ABA, PEG and NaOH) and lignin content-related features of the F5H gene family in Sorghum bicolor have not been explored. This study envisaged mining of Sorghum genomic data leading to the identification of 61 SbF5H genes. Bioinformatics analysis revealed the phylogenetic evolutionary relations, gene structures, conserved motifs, physicochemical properties, and promoter cis-acting elements related to these genes and their encoded proteins. Based on the gene structural and phylogenetic features, these 61 SbF5Hs were grouped into 4 subclasses. The in silico expression analysis revealed higher accumulation of SbF5H1 transcripts in embryo and in root under stress conditions. Similarly, Other SbF5H genes have shown expression in stem and root, thus indicating SbF5H genes involvement in Sorghum lignin biosynthesis. By exploring into the functional aspects of the F5H gene, our study sought to shed light on its significance in influencing not only the chemical makeup of lignin but also the resultant plant phenotypes. This insight into the molecular mechanisms governing lignin biosynthesis can have implications for bioenergy production and crop improvement.

7542 Androgen Receptor Oligomerization State Allows Cells to Exhibit Non-Linear Dose Responses to Androgens Resulting in Distinct Biological Outputs

Abstract Disclosure: R. Safi: None. S.E. Wardell: None. P. Watkinson: None. X. Qin: None. M. Lee: None. S. Park: None. T. Krebs: None. E. Dolan: None. T. Tsuji: None. S. Nayak: None. M. Khater: None. M. Newlin: None. M. Kirkland: None. Y. Xie: None. H. Long: None. E. Fink: None. S.W. Fanning: None. S. Runyon: None. M. Brown: None. S. Xu: None. K. Owzar: None. J.D. Norris: None. D.P. McDonnell: None. An unanswered fundamental question in androgen action is how cells recognize and respond in a non-linear fashion to different levels of androgens to elicit distinct biological outputs such as occurs in prostate cancer (PCa) cells. Indeed, most PCa express the androgen receptor (AR), and tumor growth and progression are facilitated by exceedingly low levels of systemic or intratumorally produced androgens. Paradoxically, high dose androgens have been used to treat patients with late-stage metastatic PCa. We have determined that androgen dose regulates the relative cellular abundance of AR monomers and dimers in cells and that the biological output of each oligomeric form of the receptor is different. Using in vitro systems that model exposure from castrate (low dose; LD) to eugonadal levels and above (high dose; HD) of androgens, we have determined that the global changes in gene expression are substantially different, with the changes induced by LD androgens (monomeric AR) being associated with cell proliferation, and HD androgens (dimeric AR) inducing a differentiated phenotype. A similar distinction in response to androgen levels was observed in vivo. Using a chemical biology strategy, we identified ligands which freeze AR in a monomeric form and demonstrate that these compounds faithfully recapitulate the LD biology exhibited by physiological AR agonists. Mechanistically, we determined that monomeric AR facilitates a non-genomic activation of the mTOR signaling pathway to drive proliferation, while the dimer suppresses c-MYC expression, inhibit proliferation, and drive a transcriptional program associated with a differentiated phenotype. These findings highlight the inherent liabilities in current approaches used to inhibit AR-action in prostate cancer and are instructive as to strategies that can be used to develop new therapeutics for this disease and other androgenopathies. Presentation: 6/3/2024

Growing polyion complex micelles: kinetics and mechanism of electrostatic template polymerization and assembly

HypothesisElectrostatic-templated polymerization (ETP) is a recently developed strategy for robust fabrication of stable polyion complex (PIC) micelles with regulated size and morphology, yet the kinetics and mechanism about this one pot process remain elusive. ExperimentsIn ETP method, ionic monomers are polymerized in the presence of an oppositely charged ionic-neutral diblock copolymer as template. We investigate the monomer conversion and electrostatic assembly as a function of time, under different polymerization conditions of ionic strength, pH, template/monomer molar ratio and the presence of a cross-linker. FindingsThe template copolymer accelerates the monomer conversion and formation of PIC micelles dependent on ionic strength and pH. The process follows the “Pick-up” mechanism, where monomers first convert into oligomers which complex with template to induce further chain growth and electrostatic assembly. Introducing cross-linker hardly impacts the reaction kinetics and “Pick-up” route, while it creates PIC micelles containing cross-linked ionic network assembly with the template. Further removing the template by concentrated salt provides purified ionic nanogels. The disclosed findings not only provide a better understanding of the polymerization-assembly process, but also optimize the controls of electrostatic-templated polymerization for the rational design and fabrication of diverse PIC micelles and polyelectrolyte particles.

Moesin contributes to heat shock gene response through direct binding to the Med15 subunit of the Mediator complex in the nucleus.

The members of the evolutionary conserved actin-binding Ezrin, Radixin and Moesin (ERM) protein family are involved in numerous key cellular processes in the cytoplasm. In the last decades, ERM proteins, like actin and other cytoskeletal components, have also been shown to be functional components of the nucleus; however, the molecular mechanism behind their nuclear activities remained unclear. Therefore, our primary aim was to identify the nuclear protein interactome of the single Drosophila ERM protein, Moesin. We demonstrate that Moesin directly interacts with the Mediator complex through direct binding to its Med15 subunit, and the presence of Moesin at the regulatory regions of the Hsp70Ab heat shock gene was found to be Med15-dependent. Both Moesin and Med15 bind to heat shock factor (Hsf), and they are required for proper Hsp gene expression under physiological conditions. Moreover, we confirmed that Moesin, Med15 and Hsf are able to bind the monomeric form of actin and together they form a complex in the nucleus. These results elucidate a mechanism by which ERMs function within the nucleus. Finally, we present the direct interaction of the human orthologues of Drosophila Moesin and Med15, which highlights the evolutionary significance of our finding.

Silicon Phthalocyanines Functionalized with Axial Substituents Targeting PSMA: Synthesis and Preliminary Assessment of Their Potential for PhotoDynamic Therapy of Prostate Cancer.

Photodynamic therapy (PDT) is a clinical modality based on the irradiation of different diseases, mostly tumours, with light following the selective uptake of a photosensitiser by the pathological tissue. In this study, two new silicon(IV)phtalocyanines (SiPcs) functionalized at both axial positions with a PSMA inhibitor are reported as candidate photosensitizers for PDT of prostate cancer, namely compounds SiPc-PQ(PSMAi)2 and SiPc-OSi(PSMAi)2. These compounds share the same PSMA-binding motif, but differ in the linker that connects the inhibitor moiety to the Si(IV) atom: an alkoxy (Si-O-C) bond for SiPc-PQ(PSMAi)2, and a silyloxy (Si-O-Si) bond for SiPc-OSi(PSMAi)2. Both compounds were synthesized by a facile synthetic route and fully characterized by 2D NMR, mass spectrometry and absorption/fluorescence spectrophotometry. The PDT agents showed a suitable solubility in water, where they essentially exist in monomeric form. SiPc-PQ(PSMAi)2 showed a higher singlet oxygen quantum yield ΦΔ, higher fluorescence quantum yields ΦF and better photostability than SiPc-OSi(PSMAi)2. Both compounds were efficiently taken up by PSMA(+) PC3-PIP cells, but not by PSMA(-) PC3-FLU cells. However, SiPc-PQ(PSMAi)2 showed a more specific photoinduced cytotoxicity in vitro, which is likely attributable to a better stability of its water solutions.

3′-8″- Biflavones: A Review of Their Structural Diversity, Natural Occurrence, Role in Plants, Extraction and Identification

Dimeric forms of flavonoids, known as biflavonoids, are much less studied compared to monomeric forms. It is estimated that nearly 600 different natural biflavonoids have been described to date, containing various subtypes that can be subdivided according to the position of their combinations and the nature of the subunits. The group in which two monomers are linked by a 3′-8″-C atom includes the first isolated biflavonoid ginkgetin, derivatives of amentoflavone, and several other compounds. 3′-8″-biflavones recently attracted much attention as potential molecules with biological activity such as antiviral and antimicrobial activity and as effective molecules for the treatment of neurodegenerative and metabolic diseases and in cancer therapies. With the growing interest in them as pharmacologically active molecules, there is also increasing interest in finding new natural sources of 3′-8″-biflavones and optimizing methods for their extraction and identification. Herein, we have summarized the available data on the structural diversity, natural occurrence, role in plants, extraction, and identification of 3′-8″-biflavones.

Spectroscopic insights into BSA-mediated deaggregation of m-THPC

Meta-tetra(hydroxyphenyl)chlorin (m-THPC) is among the most potent photosensitizers, known for its high singlet oxygen generation efficiency. However, its clinical effectiveness in photodynamic therapy (PDT) is compromised by its propensity to aggregate in aqueous solutions, adversely affecting its photophysical properties and therapeutic potential. A series of spectroscopic techniques, including UV-Vis absorption, fluorescence spectroscopy, and laser flash photolysis, revealed that m-THPC exhibits significant aggregation, particularly in MeOH-PBS mixtures with MeOH content below 30%. This aggregation adversely affects its photophysical properties leading to reduced fluorescence quantum yield and most importantly reducing its singlet oxygen quantum yield. This study introduces the use of bovine serum albumin (BSA) to counteract the aggregation of m-THPC, aiming to enhance its solubility, stability, and efficacy in physiological settings. Through advanced spectroscopic analyses we demonstrated that the m-THPC@BSA complex exhibits restored photophysical properties characteristic for monomeric form. Notably, the complex showed a significant restoration of the singlet oxygen quantum yield (ΦΔ = 0.21) compared to aggregated m-THPC. These results underscore the potential of BSA to preserve the monomeric form of m-THPC, mitigating aggregation-induced losses in singlet oxygen production. Our findings suggest that BSA-mediated delivery systems could play a crucial role in optimizing the clinical utility of hydrophobic photosensitizers like m-THPC.

Dynamic Luminescence Vapochromism of Pyridinium-Based Organic Salts.

Organic vapochromic materials which undergo a drastic change in their photophysical properties upon exposure to vapors or gases are attracting growing scientific attention because of their low price and wide range of possible applications. In this work, luminescence vapochromism of carbazole-pyridinium-based organic salts with a general structure of (CzPy)X (CzPy+ = 2,3-di(9H-carbazol-9-yl)pyridinium ion; X = Cl, Br or I) is reported. It was found that (CzPy)X compounds form J-aggregates, which rearranged back to monomeric form upon exposure to methanol, ethanol, acetone, and water vapors. In contrast, acetonitrile was found to promote the J-aggregation in (CzPy)X compounds by occupying the voids in their crystal lattice and pushing cations closer together. It was further demonstrated that the efficiency of J-aggregation in (CzPy)X compounds depends on the size of the anion, which was employed to realize dynamic luminescence vapochromism, with vapochromic response times ranging from a couple of minutes in (CzPy)Cl to more than an hour in (CzPy)I. In addition, (CzPy)X compounds exhibited high melting points of about 250 °C and excellent thermal stability. (CzPy)Cl and (CzPy)Br have also shown good photoluminescence quantum yields at room temperature in a solid state.

The dimerization domain of SARS CoV 2 Nucleocapsid protein is partially disordered as a monomer and forms a high affinity dynamic complex.

The SARS-CoV-2 Nucleocapsid (N) is a 419 amino acids protein that drives the compaction and packaging of the viral genome. This compaction is aided not only by protein-RNA interactions, but also by protein-protein interactions that contribute to increasing the valence of the nucleocapsid protein. Here, we focused on quantifying the mechanisms that control dimer formation. Single-molecule Förster Resonance Energy Transfer enabled us to investigate the conformations of the dimerization domain in the context of the full-length protein as well as the energetics associated with dimerization. Under monomeric conditions, we observed significantly expanded configurations of the dimerization domain (compared to the folded dimer structure), which are consistent with a dynamic conformational ensemble. The addition of unlabeled protein stabilizes a folded dimer configuration with a high mean transfer efficiency, in agreement with predictions based on known structures. Dimerization is characterized by a dissociation constant of ~ 12 nM at 23 °C and is driven by strong enthalpic interactions between the two protein subunits, which originate from the coupled folding and binding. Interestingly, the dimer structure retains some of the conformational heterogeneity of the monomeric units, and the addition of denaturant reveals that the dimer domain can significantly expand before being completely destabilized. Our findings suggest that the inherent flexibility of the monomer form is required to adopt the specific fold of the dimer domain, where the two subunits interlock with one another. We proposed that the retained flexibility of the dimer form may favor the capture and interactions with RNA, and that the temperature dependence of dimerization may explain some of the previous observations regarding the phase separation propensity of the N protein.

Insight from atomistic molecular dynamics simulations into the supramolecular assembly of the aldo-keto reductase from Trypanosoma cruzi.

Currently, Chagas disease represents an important public health problem affecting more than 8 million people worldwide. The vector of this disease is the Trypanosoma cruzi (Tc) parasite. Our research specifically focuses on the structure and aggregation states of the enzyme aldo-keto reductase of Tc (TcAKR) reported in this parasite. TcAKR belongs to the aldo-keto reductase (AKR) superfamily, enzymes that catalyze redox reactions involved in crucial biological processes. While most AKRs are found in monomeric forms, some have been reported to form dimeric and tetrameric structures. This is the case for some TcAKR. To better understand how TcAKR multimers form and remain stable, we conducted a comprehensive computational analysis using molecular dynamics (MD) simulations. Our approach to elucidating the aggregation states of TcAKR involved two strategies. Initially, we explored the dynamic behaviour of pre-assembled TcAKR dimers. Subsequently, we examined the self-aggregation of eight monomers. This investigation led to the identification of crucial residues that contribute to the stabilization of protein-protein interactions. It was also found that TcAKRs can form stable supramolecular assemblies, with each monomer typically surrounded by three first neighbours. These findings align with experimental reports of tetrameric or more complex supramolecular structures. Our computational studies could guide further experimental investigations aiming at drug development and assist in designing strategies to modulate aggregation. Atomistic molecular dynamics simulations were carried out. The TcAKR 3D model structure was obtained by homology modelling using the Swiss Model for the TcAKR sequence (GenBank accession no. EU558869). Further, we checked the model with Alphafold2 and found a high degree of similarity between models. Several tools were used to build the dimers including CLUSPRO, GRAMM-Docking, Hdock, and Py-dock. Protein superstructures were built using the PACKMOL package. CHARMM-GUI was used to set up the simulation systems. GROMACS version 2020.5 was used to perform the simulations with the CHARMM36 force field for the protein and ions and the TIP3P model for water. Further analyses were performed using VMD, GROMACS, AMBER tools, MDLovoFit, bio3d, and in-house programs.

Optical and supramolecular properties of cyclometalated palladium nanostructures with tumor targeting properties in living mice: a quantum mechanics interpretation.

The recent discovery that metallophilic interactions between cyclometalated palladium supramolecular nanostructures - with efficient tumour accumulation rate in a skin melanoma model - maintain excellent photodynamic properties even in a hypoxic microenvironment has inspired the present study focused on the theoretical predictions of optical properties of the bis-cyclometalated palladium compound in different contexts. More specifically, structural and UV/Vis absorption properties of both monomeric and dimeric forms of this anticancer drug are well reproduced with a Time-Dependent Density Functional Theoretical (TD-DFT) approach based on Exchange-Correlation (XC) hybrid functionals in conjunction with conductor-like and polarization solvation effects. A further novelty is represented by a fine investigation of the supramolecular interactions between the different subunits of the drug via dispersion force correction andQuantum Theory of Atoms in Molecules (QTAIM). This contribution while supporting the photoexcitation properties derived in laboratory following the self-assembly of monomeric units when passing from dimethyl sulfoxide (DMSO) to a H2O/DMSO mixture at 298K, shed some light on the nature of the chemical interactions modulating the formation of nano-size aggregates.

Application of computational techniques on non-covalent interactions, H-bond nature of monomeric and dimeric form of crystal structures, and topological insights of glycine glutaric acid

This study utilizes DFT to investigate and optimize the structure of Glycine Glutaric acid (GGA) crystal in both monomer and dimer forms, assessing its electronic and optical properties. Relaxed PES scanning identified potential conformers within the COOH and NH2 functional groups. FT-IR spectrum confirmed these groups and simulated spectra were correlated with the experimental data. The stable monomer was selected for detailed analysis of electronic charge transfer using MEP, FMOs, and UV–visible absorbance spectra. Non-covalent interactions, primarily O–H⋯O and N–H⋯O hydrogen bonds, were explored using optimized structures. Solvent effects, analyzed via the IEFPCM method, revealed heightened reactivity in the aqueous phase. Topological studies (AIM, LOL, ELF, and RDG) and Hirshfeld surface analysis were applied to understand inter and intramolecular contacts, with crystal packing dominated by O⋯H/H⋯O interactions contributing to 63.4 % efficiency. As per DFT prediction, the GGA exhibits strong NLO potential due to significantly higher polarizability and hyperpolarizability (⟨β⟩= 1.3618 × 10−30 e.s.u.) indicating promising nonlinear optical properties.