The Role of Hydrogen Bonding in the Raman Spectral Signals of Caffeine in Aqueous Solution.

The identification and quantification of caffeine is a common need in the food and pharmaceutical industries and lately also in the field of environmental science. For that purpose, Raman spectroscopy has been used as an analytical technique, but the interpretation of the spectra requires reliable and accurate computational protocols, especially as regards the Resonance Raman (RR) variant. Herein, caffeine solutions are sampled using Molecular Dynamics simulations. Upon quantification of the strength of the non-covalent intermolecular interactions such as hydrogen bonding between caffeine and water, UV-Vis, Raman, and RR spectra are computed. The results provide general insights into the hydrogen bonding role in mediating the Raman spectral signals of caffeine in aqueous solution. Also, by analyzing the dependence of RR enhancement on the absorption spectrum of caffeine, it is proposed that the sensitivity of the RR technique could be exploited at excitation wavelengths moderately far from 266 nm, yet achieving very low detection limits in the quantification caffeine content.

Open optimism as an "embodied-health" ethic for the information era.

This article forms part of a series on "openness," "non-linearity," and "embodied-health" in the post-physical, informational (virtual) era of society. This is vital given that the threats posed by advances in artificial intelligence call for a holistic, embodied approach. Typically, health is separated into different categories, for example, (psycho)mental health, biological/bodily health, genetic health, environmental health, or reproductive health. However, this separation only serves to undermine health; there can be no separation of health into subgroups (psychosomatics, for example). Embodied health contains no false divisions and relies on "optimism" as the key framing value. Optimism is only achieved through the mechanism/enabling condition of openness. Openness is vital to secure the embodied health for individuals and societies. Optimism demands that persons become active participants within their own lives and are not mere blank slates, painted in the colors of physical determinism (thus a move away from nihilism-which is the annihilation of freedom/autonomy/quality). To build an account of embodied health, the following themes/aims are analyzed, built, and validated: (1) a modern re-interpretation and validation of German idealism (the crux of many legal-ethical systems) and Freud; (2) ascertaining the bounded rationality and conceptual semantics of openness (which underlies thermodynamics, psychosocial relations, individual autonomy, ethics, and as being a central constitutional governmental value for many regulatory systems); (3) the link between openness and societal/individual embodied health, freedom, and autonomy; (4) securing the role of individualism/subjectivity in constituting openness; (5) the vital role of nonlinear dynamics in securing optimism and embodied health; (6) validation of arguments using the methodological scientific value of invariance (generalization value) by drawing evidence from (i) information and computer sciences, (ii) quantum theory, and (iii) bio-genetic evolutionary evidence; and (7) a validation and promotion of the inalienable role of theoretic philosophy in constituting embodied health, and how modern society denigrates embodied health, by misconstruing and undermining theoretics. Thus, this paper provides and defends an up-to-date non-physical account of embodied health by creating a psycho-physical-biological-computational-philosophical construction. Thus, this paper also brings invaluable coherence to legal and ethical debates on points of technicality from the empirical sciences, demonstrating that each field is saying the same thing.

Quantum inspired approach for denoising with application to medical imaging.

Background noise in many fields such as medical imaging poses significant challenges for accurate diagnosis, prompting the development of denoising algorithms. Traditional methodologies, however, often struggle to address the complexities of noisy environments in high dimensional imaging systems. This paper introduces a novel quantum-inspired approach for image denoising, drawing upon principles of quantum and condensed matter physics. Our approach views medical images as amorphous structures akin to those found in condensed matter physics and we propose an algorithm that incorporates the concept of mode resolved localization directly into the denoising process. Notably, our approach eliminates the need for hyperparameter tuning. The proposed method is a standalone algorithm with minimal manual intervention, demonstrating its potential to use quantum-based techniques in classical signal denoising. Through numerical validation, we showcase the effectiveness of our approach in addressing noise-related challenges in imaging and especially medical imaging, underscoring its relevance for possible quantum computing applications.

Driving forces and large scale affinity calculations for piperine/γ-cyclodxetrin complexes: Mechanistic insights from umbrella sampling simulation and DFT calculations.

Piperine (PiP), a bioactive molecule, exhibits numerous health benefits and is frequently employed as a co-delivery agent with various phytomedicines (e.g., curcumin) to enhance their bioavailability. This is attributed to PiP's inhibitory activity against drug-metabolizing proteins, notably CYP3A4. Nevertheless, PiP encounters solubility challenges addressed in this study using cyclodextrins (CDs). Specifically, γ-CD and its derivatives, Hydroxypropyl-γ-CD (HP-γ-CD), and Octakis (6-O-sulfo)-γ-CD (Octakis-S-γ-CD), were employed to form supramolecular complexes with PiP. The conformational space of the complexes was assessed through 1 µs molecular dynamics simulations and umbrella sampling. Additionally, quantum mechanical calculations using wB97X-D dispersion-corrected DFT functional and 6-311 + G(d,p) basis set were conducted on the complexes to examine the thermodynamics and kinetic stability. Results indicated that Octakis-S-γ-CD exhibits superior host capabilities for PiP, with the most favorable complexation energy (-457.05 kJ/mol), followed by HP-γ-CD (-249.16 kJ/mol). Furthermore, two conformations of the Octakis-S-γ-CD/PiP complex were explored to elucidate the optimal binding orientation of PiP within the binding pocket of Octakis-S-γ-CD. Supramolecular chemistry relies significantly on non-covalent interactions. Therefore, our investigation extensively explores the critical atoms involved in these interactions, elucidating the influence of substituted groups on the stability of inclusion complexes. This comprehensive analysis contributes to emphasizing the γ-CD derivatives with improved host capacity.

COSMOPharm: Drug-Polymer Compatibility of Pharmaceutical Amorphous Solid Dispersions from COSMO-SAC.

The quantum mechanics-aided COSMO-SAC activity coefficient model is applied and systematically examined for predicting the thermodynamic compatibility of drugs and polymers. The drug-polymer compatibility is a key aspect in the rational selection of optimal polymeric carriers for pharmaceutical amorphous solid dispersions (ASD) that enhance drug bioavailability. The drug-polymer compatibility is evaluated in terms of both solubility and miscibility, calculated using standard thermodynamic equilibrium relations based on the activity coefficients predicted by COSMO-SAC. As inherent to COSMO-SAC, our approach relies only on quantum-mechanically derived σ-profiles of the considered molecular species and involves no parameter fitting to experimental data. All σ-profiles used were determined in this work, with those of the polymers being derived from their shorter oligomers by replicating the properties of their central monomer unit(s). Quantitatively, COSMO-SAC achieved an overall average absolute deviation of 13% in weight fraction drug solubility predictions compared to experimental data. Qualitatively, COSMO-SAC correctly categorized different polymer types in terms of their compatibility with drugs and provided meaningful estimations of the amorphous-amorphous phase separation. Furthermore, we analyzed the sensitivity of the COSMO-SAC results for ASD to different model configurations and σ-profiles of polymers. In general, while the free volume and dispersion terms exerted a limited effect on predictions, the structures of oligomers used to produce σ-profiles of polymers appeared to be more important, especially in the case of strongly interacting polymers. Explanations for these observations are provided. COSMO-SAC proved to be an efficient method for compatibility prediction and polymer screening in ASD, particularly in terms of its performance-cost ratio, as it relies only on first-principles calculations for the considered molecular species. The open-source nature of both COSMO-SAC and the Python-based tool COSMOPharm, developed in this work for predicting the API-polymer thermodynamic compatibility, invites interested readers to explore and utilize this method for further research or assistance in the design of pharmaceutical formulations.

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 and Quantum 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.

Insights into Cis-Amide-Modified Carbon Nanotubes for Selective Purification of CH4 and H2 from Gas Mixtures: A Comparative DFT Study.

Among a plethora of mixtures, the methane (CH4) and hydrogen (H2) mixture has garnered considerable attention for multiple reasons, especially in the framework of energy production and industrial processes as well as ecological considerations. Despite the fact that the CH4/H2 mixture performs many critical tasks, the presence of other gases, such as carbon dioxide, sulfur compounds like H2S, and water vapor, leads to many undesirable consequences. Thus purification of this mixture from these gases assumes considerable relevance. In the current research, first-principle calculations in the frame of density functional theory are carried out to propose a new functional group for vertically aligned carbon nanotubes (VA-CNTs) interacting preferentially with polar molecules rather than CH4 and H2 in order to obtain a more efficient methane and hydrogen separations The binding energies associated with the interactions between several chemical groups and target gases were calculated first, and then a functional group formed by a modified ethylene glycol and acetyl amide was selected. This functional group was attached to the CNT edge with an appropriate diameter, and hence the binding energies with the target gases and steric hindrance were evaluated. The binding energy of the most polar molecule (H2O) was found to be more than six times higher than that of H2, indicating a significant enhancement of the nanotube tip's affinity toward polar gases. Thus, this functionalization is beneficial for enhancing the capability of highly packed functionalized VA-CNT membranes to purify CH4/H2 gas mixtures.

Computational discovery of dual potential inhibitors of SARS-CoV-2 spike/ACE2 and Mpro: 3D-pharmacophore, docking-based virtual screening, quantum mechanics and molecular dynamics.

To find drugs against COVID-19, caused by the SARS-CoV-2, promising targets include the fusion of the viral spike with the human angiotensin-converting enzyme 2 (ACE2) as well as the main protease (Mpro). These proteins are responsible for viral entry and replication, respectively. We combined several state-of-the-art computational methods, including, protein-ligand interaction fingerprint, 3D-pharmacophores, molecular-docking, MM-GBSA, DFT, and MD simulations to explore two databases: ChEMBL and NANPDB to identify molecules that could both block spike/ACE2 fusion and inhibit Mpro. A total of 1,690,649 compounds from the two databases were screened using the pharmacophore model obtained from PLIF analysis. Five recent complexes of Mpro co-crystallized with different ligands were used to generate the pharmacophore model, allowing 4,829 compounds that passed this prefilter. These were then submitted to molecular docking against Mpro. The 5% top-ranked docking hits from docking result having scores < -8.32 kcal mol-1 were selected and then docked against spike/ACE2. Only four compounds: ChEMBL244958, ChEMBL266531, ChEMBL3680003, and 1-methoxy-3-indolymethyl glucosinolate (4) displayed binding energies < - 8.21 kcal mol-1 (for the native ligand) were considered as putative dual-target inhibitors. Furthermore, predictive ADMET, MM-GBSA and DFT/6-311G(d,p) were performed on these compounds and compared with those of well-known antivirals. DFT calculations showed that ChEMBL244958 and compound 4 had significant predicted reactivity values. Molecular dynamics simulations of the docked complexes were run for 100 ns and used to validate the stability docked poses and to confirm that these hits are putative dual binders of the spike/ACE2 and the Mpro.

Mutation-induced shift of the photosystem II active site reveals insight into conserved water channels.

Photosystem II (PSII) is the water-plastoquinone photo-oxidoreductase central to oxygenic photosynthesis. PSII has been extensively studied for its ability to catalyze light-driven water oxidation at a Mn4CaO5 cluster called the oxygen-evolving complex (OEC). Despite these efforts, the complete reaction mechanism for water oxidation by PSII is still heavily debated. Previous mutagenesis studies have investigated the roles of conserved amino acids, but these studies have lacked a direct structural basis that would allow for a more meaningful interpretation. Here, we report a 2.14-Å resolution cryo-EM structure of a PSII complex containing the substitution Asp170Glu on the D1 subunit. This mutation directly perturbs a bridging carboxylate ligand of the OEC, which alters the spectroscopic properties of the OEC without fully abolishing water oxidation. The structure reveals that the mutation shifts the position of the OEC within the active site without markedly distorting the Mn4CaO5 cluster metal-metal geometry, instead shifting the OEC as a rigid body. This shift disturbs the hydrogen-bonding network of structured waters near the OEC, causing disorder in the conserved water channels. This mutation-induced disorder appears consistent with previous FTIR spectroscopic data. We further show using quantum mechanics/molecular mechanics methods that the mutation-induced structural changes can affect the magnetic properties of the OEC by altering the axes of the Jahn-Teller distortion of the Mn(III) ion coordinated to D1-170. These results offer new perspectives on the conserved water channels, the rigid body property of the OEC, and the role of D1-Asp170 in the enzymatic water oxidation mechanism.

Mario Ageno and the status of biophysics.

This essay focuses on Mario Ageno (1915-1992), initially director of the physics laboratory of the Italian National Institute of Health and later professor of biophysics at Sapienza University of Rome. A physicist by training, Ageno became interested in explaining the special characteristics of living organisms origin of life by means of quantum mechanics after reading a book by Schrödinger, who argued that quantum mechanics was consistent with life but that new physical principles must be found. Ageno turned Schrödinger's view into a long-term research project. He aimed to translate Schrödinger's ideas into an experimental programme by building a physical model for at least a very simple living organism. The model should explain the transition from the non-living to the living. His research, however, did not lead to the expected results, and in the 1980s and the 1990s he focused on its epistemological aspect, thinking over the tension between the lawlike structure of physics and the historical nature of biology. His reflections led him to focus on the nature of the theory of evolution and its broader scientific meaning.

Delayed-choice entanglement swapping experiments: No evidence for timelike entanglement.

In recent years, there has been a growing interest in the possibility of temporal nonlocality, mirroring the spatial nonlocality supposedly evidenced by the Bell correlations. In this context, Glick (2019) has argued that timelike entanglement and temporal nonlocality is demonstrated in delayed-choice entanglement swapping (DCES) experiments, like that of Ma et al. (2012), Megidish et al. (2013) and Hensen et al. (2015). I will argue that a careful analysis of these experiments shows that they in fact display nothing more than "ordinary" spacelike entanglement, and that any purported timelike entanglement is an artefact of selection bias. Regardless any other reason one may have for challenging the assumption of temporal locality, timelike entanglement as evidenced by these experiments is not among them. I conclude by discussing what lessons on the nature of entanglement might be drawn from an examination of DCES experiments.

Hamiltonian Computational Chemistry: Geometrical Structures in Chemical Dynamics and Kinetics.

The common geometrical (symplectic) structures of classical mechanics, quantum mechanics, and classical thermodynamics are unveiled with three pictures. These cardinal theories, mainly at the non-relativistic approximation, are the cornerstones for studying chemical dynamics and chemical kinetics. Working in extended phase spaces, we show that the physical states of integrable dynamical systems are depicted by Lagrangian submanifolds embedded in phase space. Observable quantities are calculated by properly transforming the extended phase space onto a reduced space, and trajectories are integrated by solving Hamilton's equations of motion. After defining a Riemannian metric, we can also estimate the length between two states. Local constants of motion are investigated by integrating Jacobi fields and solving the variational linear equations. Diagonalizing the symplectic fundamental matrix, eigenvalues equal to one reveal the number of constants of motion. For conservative systems, geometrical quantum mechanics has proved that solving the Schrödinger equation in extended Hilbert space, which incorporates the quantum phase, is equivalent to solving Hamilton's equations in the projective Hilbert space. In classical thermodynamics, we take entropy and energy as canonical variables to construct the extended phase space and to represent the Lagrangian submanifold. Hamilton's and variational equations are written and solved in the same fashion as in classical mechanics. Solvers based on high-order finite differences for numerically solving Hamilton's, variational, and Schrödinger equations are described. Employing the Hénon-Heiles two-dimensional nonlinear model, representative results for time-dependent, quantum, and dissipative macroscopic systems are shown to illustrate concepts and methods. High-order finite-difference algorithms, despite their accuracy in low-dimensional systems, require substantial computer resources when they are applied to systems with many degrees of freedom, such as polyatomic molecules. We discuss recent research progress in employing Hamiltonian neural networks for solving Hamilton's equations. It turns out that Hamiltonian geometry, shared with all physical theories, yields the necessary and sufficient conditions for the mutual assistance of humans and machines in deep-learning processes.

Does Quantum Mechanics Require "Conspiracy"?

Quantum states containing records of incompatible outcomes of quantum measurements are valid states in the tensor-product Hilbert space. Since they contain false records, they conflict with the Born rule and with our observations. I show that excluding them requires a fine-tuning to an extremely restricted subspace of the Hilbert space that seems "conspiratorial", in the sense that (1) it seems to depend on future events that involve records (including measurement settings) and on the dynamical law (normally thought to be independent of the initial conditions), and (2) it violates Statistical Independence, even when it is valid in the context of Bell's theorem. To solve the puzzle, I build a model in which, by changing the dynamical law, the same initial conditions can lead to different histories in which the validity of records is relative to the new dynamical law. This relative validity of the records may restore causality, but the initial conditions still must depend, at least partially, on the dynamical law. While violations of Statistical Independence are often seen as non-scientific, they turn out to be needed to ensure the validity of records and our own memories and, by this, of science itself. A Past Hypothesis is needed to ensure the existence of records and turns out to require violations of Statistical Independence. It is not excluded that its explanation, still unknown, ensures such violations in the way needed by local interpretations of quantum mechanics. I suggest that an as-yet unknown law or superselection rule may restrict the full tensor-product Hilbert space to the very special subspace required by the validity of records and the Past Hypothesis.

Cavity-mediated long-range interactions in levitated optomechanics.

The ability to engineer cavity-mediated interactions has emerged as a powerful tool for the generation of non-local correlations and the investigation of non-equilibrium phenomena in many-body systems. Levitated optomechanical systems have recently entered the multiparticle regime, which promises the use of arrays of strongly coupled massive oscillators to explore complex interacting systems and sensing. Here we demonstrate programmable cavity-mediated interactions between nanoparticles in vacuum by combining advances in multiparticle optical levitation and cavity-based quantum control. The interaction is mediated by photons scattered by spatially separated particles in a cavity, resulting in strong coupling that is long-range in nature. We investigate the scaling of the interaction strength with cavity detuning and interparticle separation and demonstrate the tunability of interactions between different mechanical modes. Our work will enable the exploration of many-body effects in nanoparticle arrays with programmable cavity-mediated interactions, generating entanglement of motion, and the use of interacting particle arrays for optomechanical sensing.

Computational study on the endocrine-disrupting metabolic activation of Benzophenone-3 catalyzed by cytochrome P450 1A1: A QM/MM approach.

Predicting the metabolic activation mechanism and potential hazardous metabolites of environmental endocrine-disruptors is a challenging and significant task in risk assessment. Here the metabolic activation mechanism of benzophenone-3 catalyzed by P450 1A1 was investigated by using Molecular Dynamics, Quantum Mechanics/Molecular Mechanics and Density Functional Theory approaches. Two elementary reactions involved in the metabolic activation of BP-3 with P450 1A1: electrophilic addition and hydrogen abstraction reactions were both discussed. Further conversion reactions of epoxidation products, ketone products and the formaldehyde formation reaction were investigated in the non-enzymatic environment based on previous experimental reports. Binding affinities analysis of benzophenone-3 and its metabolites to sex hormone binding globulin indirectly demonstrates that they all exhibit endocrine-disrupting property. Toxic analysis shows that the eco-toxicity and bioaccumulation values of the benzophenone-3 metabolites are much lower than those of benzophenone-3. However, the metabolites are found to have skin-sensitization effects. The present study provides a deep insight into the biotransformation process of benzophenone-3 catalyzed by P450 1A1 and alerts us to pay attention to the adverse effects of benzophenone-3 and its metabolites in human livers.

When Tautomers Matter: UV-Vis Absorption Spectra of Hypoxanthine in Aqueous Solution from Fully Atomistic Simulations.

The UV-Vis spectrum of the solvated purine derivative Hypoxanthine (HYX) is investigated using the Quantum Mechanics/Fluctuating Charges (QM/FQ) multiscale approach combined with a sampling of configurations through atomistic Molecular Dynamics (MD) simulations. Keto 1H7H and 1H9H tautomeric forms of HYX are the most stable in aqueous solution and form different stable complexes with the surrounding water molecules, ultimately affecting the electronic absorption spectra. The final simulated spectrum resulting from the combination of the individual spectra of tautomers agrees very well with most of the characteristics in the measured spectrum. The importance of considering the effect of the solute tautomers and, in parallel, the contribution of the different solvent arrangements around the solute when modeling spectral properties, is highlighted. In addition, the high quality of the computed spectra leads to suggesting an alternative way for acquiring tautomeric populations from combined computational/experimental spectra.

Chemical diversity in angiosperms - monoterpene synthases control complex reactions that provide the precursors for ecologically and commercially important monoterpenoids.

Monoterpene synthases (MTSs) catalyze the first committed step in the biosynthesis of monoterpenoids, a class of specialized metabolites with particularly high chemical diversity in angiosperms. In addition to accomplishing a rate enhancement, these enzymes manage the formation and turnover of highly reactive carbocation intermediates formed from a prenyl diphosphate substrate. At each step along the reaction path, a cationic intermediate can be subject to cyclization, migration of a proton, hydride, or alkyl group, or quenching to terminate the sequence. However, enzymatic control of ligand folding, stabilization of specific intermediates, and defined quenching chemistry can maintain the specificity for forming a signature product. This review article will discuss our current understanding of how angiosperm MTSs control the reaction environment. Such knowledge allows inferences about the origin and regulation of chemical diversity, which is pertinent for appreciating the role of monoterpenoids in plant ecology but also for aiding commercial efforts that harness the accumulation of these specialized metabolites for the food, cosmetic, and pharmaceutical industries.

Accurate prediction of dynamic protein-ligand binding using P-score ranking.

Protein-ligand binding prediction typically relies on docking methodologies and associated scoring functions to propose the binding mode of a ligand in a biological target. Significant challenges are associated with this approach, including the flexibility of the protein-ligand system, solvent-mediated interactions, and associated entropy changes. In addition, scoring functions are only weakly accurate due to the short time required for calculating enthalpic and entropic binding interactions. The workflow described here attempts to address these limitations by combining supervised molecular dynamics with dynamical averaging quantum mechanics fragment molecular orbital. This combination significantly increased the ability to predict the experimental binding structure of protein-ligand complexes independent from the starting position of the ligands or the binding site conformation. We found that the predictive power could be enhanced by combining the residence time and interaction energies as descriptors in a novel scoring function named the P-score. This is illustrated using six different protein-ligand targets as case studies.

On algebraic naturalism and metaphysical indeterminacy in quantum mechanics.

I propose a technique for identifying fundamental properties using structures already present in physical theories. I argue that, in conjunction with a particular naturalistic commitment, that I dub 'algebraic naturalism', these structures can be used to generate a standard of metaphysical determinacy. This standard can be used to rule out the possibility of a virulent strain of 'deep' metaphysical indeterminacy that has been imputed to quantum mechanics.

Advances in Semiconductor Lasers Based on Parity-Time Symmetry.

Semiconductor lasers, characterized by their high efficiency, small size, low weight, rich wavelength options, and direct electrical drive, have found widespread application in many fields, including military defense, medical aesthetics, industrial processing, and aerospace. The mode characteristics of lasers directly affect their output performance, including output power, beam quality, and spectral linewidth. Therefore, semiconductor lasers with high output power and beam quality are at the forefront of international research in semiconductor laser science. The novel parity-time (PT) symmetry mode-control method provides the ability to selectively modulate longitudinal modes to improve the spectral characteristics of lasers. Recently, it has gathered much attention for transverse modulation, enabling the output of fundamental transverse modes and improving the beam quality of lasers. This study begins with the basic principles of PT symmetry and provides a detailed introduction to the technical solutions and recent developments in single-mode semiconductor lasers based on PT symmetry. We categorize the different modulation methods, analyze their structures, and highlight their performance characteristics. Finally, this paper summarizes the research progress in PT-symmetric lasers and provides prospects for future development.