Organic Molecules In Aqueous Solution Research Articles

Predictions of Colloidal Molecular Aggregation Using AI/ML Models.

To facilitate the triage of hits from small molecule screens, we have used various AI/ML techniques and experimentally observed data sets to build models aimed at predicting colloidal aggregation of small organic molecules in aqueous solution. We have found that Naïve Bayesian and deep neural networks outperform logistic regression, recursive partitioning tree, support vector machine, and random forest techniques by having the lowest balanced error rate (BER) for the test set. Derived predictive classification models consistently and successfully discriminated aggregator molecules from nonaggregator hits. An analysis of molecular descriptors in favor of colloidal aggregation confirms previous observations (hydrophobicity, molecular weight, and solubility) in addition to undescribed molecular descriptors such as the fraction of sp3 carbon atoms (Fsp3), and electrotopological state of hydroxyl groups (ES_Sum_sOH). Naïve Bayesian modeling and scaffold tree analysis have revealed chemical features/scaffolds contributing the most to colloidal aggregation and nonaggregation, respectively. These results highlight the importance of scaffolds with high Fsp3 values in promoting nonaggregation. Matched molecular pair analysis (MMPA) has also deciphered context-dependent substitutions, which can be used to design nonaggregator molecules. We found that most matched molecular pairs have a neutral effect on aggregation propensity. We have prospectively applied our predictive models to assist in chemical library triage for optimal plate selection diversity and purchase for high throughput screening (HTS) in drug discovery projects.

Aryl-Extended and Super Aryl-Extended Calix[4]pyrroles: Design, Synthesis, and Applications.

ConspectusProteins exhibit high-binding affinity and selectivity, as well as remarkable catalytic performance. Their binding pockets are hydrophobic but also contain polar and charged groups to contribute to the binding of polar organic molecules in aqueous solution. In the past decades, the synthesis of biomimetic receptors featuring sizable aromatic cavities equipped with converging polar groups has received considerable attention. "Temple" cages, naphthotubes, and aryl-extended calix[4]pyrroles are privileged examples of synthetic scaffolds displaying functionalized hydrophobic cavities capable of binding polar substrates. In particular, calix[4]pyrroles are macrocycles containing four pyrrole rings connected through their pyrrolic 2- and 5-positions by tetra-substituted sp3 carbon atoms (meso-substituents). In 1996, Sessler introduced the meso-octamethyl calix[4]pyrrole as an outstanding receptor for anion binding. Independently, Sessler and Floriani also showed that the introduction of aryl substituents in the meso-positions produced aryl-extended calix[4]pyrroles as a mixture of configurational isomers. In addition, aryl-extended calix[4]pyrroles bearing two and four meso-aryl substituents (walls) were reported. The cone conformation of "two-wall" αα-aryl-extended calix[4]pyrroles features an aromatic cleft with a polar binding site defined by four converging pyrrole NHs. On the other hand, "four-wall" αααα-calix[4]pyrrole isomers possess a deep polar aromatic cavity closed at one end by the converging pyrrole NHs. Because of their functionalized interior, aryl-extended calix[4]pyrroles are capable of binding anions, ion-pairs, and electron-rich neutral molecules in organic solvents. However, in water, they are restricted to the inclusion of neutral polar guests.Since the early 2000s, our research group has been involved in the design and synthesis of "two-wall" and "four-wall" aryl-extended calix[4]pyrroles and their derivatives, such as aryl-extended calix[4]pyrrole cavitands and super aryl-extended calix[4]pyrroles. In this Account, we mainly summarize our own results on the binding of charged and neutral polar guests with these macrocyclic receptors in organic solvents and in water. We also describe the applications of calix[4]pyrrole derivatives in the sensing of creatinine, the facilitated transmembrane transport of anions and amino acids, and the monofunctionalization of bis-isonitriles. Moreover, we explain the use of calix[4]pyrrole receptors as model systems for the quantification of anion-π interactions and the hydrophobic effect. Finally, we discuss the self-assembly of dimeric capsules and unimolecular metallo-cages based on calix[4]pyrrole scaffolds. We comment on their binding properties, as well as on those of bis-calix[4]pyrroles having a fully covalent structure.In molecular recognition, aryl-extended calix[4]pyrroles and their derivatives are considered valuable receptors owing to their ability to interact with a wide variety of electron-rich, neutral, and charged guests. Calix[4]pyrrole scaffolds have also been applied in the development of molecular sensors, ionophores, transmembrane carriers, supramolecular protecting groups and molecular containers modulating chemical reactivity, among others. We believe that the design of new calix[4]pyrrole receptors and the investigation of their binding properties may lead to promising applications in many research areas, such as supramolecular catalysis, chemical biology and materials science. We hope that this Account will serve to spread the knowledge of the supramolecular chemistry of calix[4]pyrroles among supramolecular and nonsupramolecular chemists alike.

Theoretical study of Ponceau S oxidation using the electro-Fenton process under optimal operational conditions.

Electrochemical methods as one of the Advanced Oxidation Processes (AOPs) have been applied effectively to the degradation of recalcitrant organic molecules in aqueous solutions. In the present study, the performance of the electro-Fenton (EF) process on the oxidation of Ponceau S(PS) dye was studied. The experimental study performed at the optimal factors like the solution pH, the PS concentration and the ferrous ions dose provided 74.35% of PS degradation. The results, however, showed a decreased removal efficiency of PS when using sodium sulphate as the supporting electrolyte. From a theoretical point of view, the hydroxyl radical being an electron acceptor and the PS dye an electron donor, from a theoretical point of view, the hydroxyl radical being an electron acceptor and the PS dye an electron donor, furthermore, the nitrogen atom 2N being the most nucleophilic site of the PS dye with the most electrophilic site of the hydroxyl radical being the oxygen atom, the first stage of the reaction between PS and the hydroxyl radical was suggested.

SOMAS: a platform for data-driven material discovery in redox flow battery development

Aqueous organic redox flow batteries offer an environmentally benign, tunable, and safe route to large-scale energy storage. The energy density is one of the key performance parameters of organic redox flow batteries, which critically depends on the solubility of the redox-active molecule in water. Prediction of aqueous solubility remains a challenge in chemistry. Recently, machine learning models have been developed for molecular properties prediction in chemistry and material science. The fidelity of a machine learning model critically depends on the diversity, accuracy, and abundancy of the training datasets. We build a comprehensive open access organic molecular database “Solubility of Organic Molecules in Aqueous Solution” (SOMAS) containing about 12,000 molecules that covers wider chemical and solubility regimes suitable for aqueous organic redox flow battery development efforts. In addition to experimental solubility, we also provide eight distinctive quantum descriptors including optimized geometry derived from high-throughput density functional theory calculations along with six molecular descriptors for each molecule. SOMAS builds a critical foundation for future efforts in artificial intelligence-based solubility prediction models.

A highly sensitive and multi-responsive Tb-MOF fluorescent sensor for the detection of Pb2+, Cr2O72−, B4O72−, aniline, nitrobenzene and cefixime

A terbium metal organic framework (Tb-MOF), namely {[Tb(dppa)(H2O)2]·dima·H2O·0.5O}n (1), (H4dppa = 5-(3′4′-dicarboxylphenoxy)isophthalic acid, dima = dimethylamine, which is formed by the decomposition of DMF in aqueous solution at high temperature.) was prepared and characterized. Tb-MOF is connected by (dppa)4- ligands via μ4:η1,η2,η2,η2 coordination mode to form a two-dimensional wavy network, which is extended to three-dimensional supramolecular structures based on hydrogen bonding. Tb-MOF has excellent fluorescence properties, which can be used for fluorescence recognition and quantitative determination of cation and anion, antibiotics and small organic molecules in aqueous solution with high sensitivity and good selectivity. Tb-MOF showed enhanced fluorescene for Pb2+ and B4O72− ions, while quenching fluorescence for Cr2O72− ion. Noticeably, this is the first time that Pb2+ and B4O72− ions have been detected by a MOF-based fluorescence sensor using a fluorescence enhancement mechanism. More interestingly, Tb-MOF can quantitatively detect aniline (ANI) in aqueous solution by ratiometric fluorescence sensing. In addition, Tb-MOF has great selectivity and sensitivity for detecting of nitrobenzene (NB) and cefixime (CEF). In particular, when NB concentration is 50 μM, the fluorescence quenching rate of Tb-MOF reaches 99.6%. Therefore, this paper introduces a highly sensitive and multi-responsive Tb-MOF sensor, which can be used to detect Pb2+, B4O72−, Cr2O72−, ANI, NB and CEF with fast response speed and good selectivity.

A polarizable three-layer frozen density embedding/molecular mechanics approach.

We present a novel multilayer polarizable embedding approach in which the system is divided into three portions, two of which are treated using density functional theory and their interaction is based on frozen density embedding (FDE) theory, and both also mutually interact with a polarizable classical layer described using an atomistic model based on fluctuating charges (FQ). The efficacy of the model is demonstrated by extending the formalism to linear response properties and applying it to the simulation of the excitation energies of organic molecules in aqueous solution, where the solute and the first solvation shell are treated using FDE, while the rest of the solvent is modeled using FQ charges.

Elastomeric Silicone Sponges for Bleach Delivery

Topical disinfection protocols to inactivate organisms, particularly on high contact surfaces, have become increasingly important. A classical oxidative agent, sodium hypochlorite (bleach), has many benefits, but can be problematic during applications because of its ability to oxidize the organic polymers in which it is contained. We demonstrate that bleach-containing elastomeric sponges are readily created in one step at room temperature from thiopropyl-modified silicone oils; sodium hypochlorite induces disulfide cross-linking and a foam structure due, in part, to the concomitant formation of sulfonates. No surfactants are required. The morphology of the bleach-containing silicone sponge is tunable by the aqueous bleach solution concentration and the water/silicone ratio used. The resulting silicone sponge contains excess bleach that can be released gradually, as shown by its ability to oxidize organic molecules in aqueous solution, either directly or after dehydration/rehydration; the latter process provides a way to store the bleach-containing material in dry form. Such foams exhibit enhanced sustainability as, we show, they can be converted back to thiopropylsilicone oils by reduction using hydrosilicones. The resulting oils can be re-cross-linked, completing the life cycle.

Calculation of Linear and Non-linear Electric Response Properties of Systems in Aqueous Solution: A Polarizable Quantum/Classical Approach with Quantum Repulsion Effects.

We present a computational study of polarizabilities and hyperpolarizabilities of organic molecules in aqueous solutions, focusing on solute–water interactions and the way they affect a molecule’s linear and non-linear electric response properties. We employ a polarizable quantum mechanics/molecular mechanics (QM/MM) computational model that treats the solute at the QM level while the solvent is treated classically using a force field that includes polarizable charges and dipoles, which dynamically respond to the solute’s quantum-mechanical electron density. Quantum confinement effects are also treated by means of a recently implemented method that endows solvent molecules with a parametric electron density, which exerts Pauli repulsion forces upon the solute. By applying the method to a set of aromatic molecules in solution we show that, for both polarizabilities and first hyperpolarizabilities, observed solution values are the result of a delicate balance between electrostatics, hydrogen-bonding, and non-electrostatic solute solvent interactions.

Linear correlation models for the redox potential of organic molecules in aqueous solutions.

In this study, we use the molecular orbital energy approximation (MOEA) and the energy difference approximation (EDA) to build linear correlation models for the redox potentials of 53 organic compounds in aqueous solutions. The molecules evaluated include nitroxides, phenols, and amines. Both the MOEA and EDA methods yield similar correlation models, however, the MOEA method is less computationally expensive. Correlation coefficients (R2) below 0.3 and mean absolute errors above 0.25V were found for correlation models built without solvent effects. When explicit water molecules and a continuum solvent model are added to the calculations, correlation coefficients close to 0.8 are reached, and mean absolute errors below 0.18V are obtained. The incorporation of solvent effects is necessary for good correlation models, particularly for redox processes of charged molecules in aqueous solutions. A comparison of the correlation models from different methodologies is provided. Graphical abstract.

Photo‐Fenton‐peroxide process using FE (II)‐embedded composites based on activated carbon: Characterization of catalytic tests

AbstractCost‐efficient Fenton‐like catalysts for the removal of organic molecules in aqueous solutions were elaborated by a simple process. Porous activated carbons (ACs) were directly impregnated with a precursor solution using the wet impregnation method. Their efficiency as Fenton‐like catalysts was studied. Photo‐Fenton tests were performed to establish the performance of the prepared Fe‐impregnated activated carbons in relation to the degradation of an organic pollutant (Indigo Carmine) model in aqueous solution, under different conditions. Photo‐catalytic tests were carried out by means of a laboratory photo‐reactor (UV‐Consulting Peschl). The influence of several parameters such as solution pH value, initial concentration of the model pollutant, and hydrogen peroxide dose on the process performance was investigated. The ACs and prepared catalysts were characterized by nitrogen adsorption‐desorption isotherms at 77 K, SEM, and thermogravimetric analyses. The total Fe content of the synthesized composites was estimated by the phenanthroline method using UV‐vis spectrophotometry. The results show an increase in the degradation rate when the heterogeneous photo‐Fenton process is conducted with an ozone generating UV lamp.

The Partner Does Matter: The Structure of Heteroaggregates of Acridine Orange in Water.

Self-assembly of organic molecules in aqueous solutions is governed by a delicate entropy/enthalpy balance. Even small changes in their intermolecular interactions can cause critical changes in the structure of the aggregates and their spectral properties. The experimental results reported here demonstrate that protonated cations of acridine orange, acridine, and acridin-9-amine form stable J-heteroaggregates when in water. The structures of these aggregates are justified by the homonuclear 1H cross-relaxation nuclear magnetic resonance (NMR). The absorption and fluorescence of these aggregates deviate characteristically from the known H-homoaggregates of the protonated cations of acridine orange. The latter makes acridine orange a handy optical sensor for soft matter studies.

Layer-by-Layer Assembly of SAM-supported Porphyrin-based Metal Organic Frameworks for Molecular Recognition

The development of the sensing systems based on the ultrathin films of functional metal organic networks as efficient synthetic alternative to molecular biosensors is in the focus of intense research. Herein we report how to fabricate uniformly structured surface-attached metal organic frameworks (SURMOFs) from zinc complex of meso-carboxyphenyl-substituted porphyrin and zinc acetate as films on the surface of self-assembled monolayers of silanes and thiols. The layer-by-layer self-assembly with shortened time of the layer deposition at room temperature was applied to obtain 5-layer SURMOFs with high crystallinity, which was confirmed by X-ray diffraction. These SAM-supported SURMOF films were used as sensing layers for qualitative response to organic molecules in aqueous solutions. By using surface plasmon resonance spectroscopy, we showed that the SURMOFs do not bind 4-nitrophenol and uracil whereas they are capable of absorption of purine compounds such as adenine and adenosine 5-monophosphate. This binding is a size sensitive process in favor to adenine suggesting the effect of the SURMOF structure on the molecular recognition. The UV-vis spectroscopy study of the process indicated that the recognition of purines by the porphyrin-based SURMOF proceeds through the interactions of the amine groups with zinc ions in metal clusters rather than with the central metal ions in porphyrin cores. Our findings provide an insight into the sensing properties of the porphyrin-based SURMOFs that is useful for further advancements in fabrication of responsive thin films for biologically relevant analytes.

Robust Free Energy Perturbation Protocols for Creating Molecules in Solution.

Accurate methods to estimate free energies play an important role for studying diverse condensed-phase problems in chemistry and biochemistry. The most common methods used in conjunction with molecular dynamics (MD) and Monte Carlo statistical mechanics (MC) simulations are free energy perturbation (FEP) and thermodynamic integration (TI). For common applications featuring the conversion of one molecule to another, simulations are run in stages or multiple "λ-windows" to promote convergence of the results. For computation of absolute free energies of solvation or binding, calculations are needed in which the solute is typically annihilated in the solvent and in the complex. The present work addresses identification of optimal protocols for such calculations, specifically, the creation/annihilation of organic molecules in aqueous solution. As is common practice, decoupling of the perturbations for electrostatic and Lennard-Jones interactions was performed. Consistent with earlier reports, FEP calculations for molecular creations are much more efficient, while annihilations require many more windows and may converge to incorrect values. Strikingly, we find that as few as four windows may be adequate for creation calculations for solutes ranging from argon to ethylbenzene. For a larger druglike molecule, MIF180, which contains 22 non-hydrogen atoms and three rotatable bonds, 10 creation windows are found to be adequate to yield the correct free energy of hydration. Convergence is impeded with procedures that use any sampling in the annihilation direction, and there is no need for postprocessing methods such as the Bennett acceptance ratio (BAR).

Time-resolved photoelectron spectroscopy of organic molecules in aqueous solutions

We use time-resolved photoelectron spectroscopy with wavelength-selected XUV femtosecond pulses to study photoinduced dynamics of organic molecules in solutions at millimolar concentrations. Upon electronic excitation we observe relaxation processes, such as excited state intramolecular proton transfer and trans-cis isomerization.

Design of multiple efficient molecular logic devices based on molecular systems containing bovine serum albumin and 5-sulfosalicylic acid

Several logic gates, which are commonly designed with DNA or organic molecules, rely on only one output mode. Here, a new molecular device was designed and constructed by combining bovine serum albumin and 5-sulfosalicylic acid. When MoO42―, Tris(hydroxymethyl)aminomethane, EDTAH2Na2, Al3+, Trichloroacetic acid are used as inputs, changes in the fluorescent intensity at 350 nm and 406 nm were observed via FRET. Four molecular devices as a half-adder and three digital logic circuits were successfully constructed on the unimolecular platform by employing emission properties at different wavelengths as outputs. The advantage of the combined system was that many different functional molecular devices could be designed and assembled by employing protein and various organic molecules in aqueous solution.

Improved Quantum Chemical NMR Chemical Shift Prediction of Metabolites in Aqueous Solution toward the Validation of Unknowns.

A quantum-chemistry based protocol, termed MOSS-DFT, is presented for the prediction of 13C and 1H NMR chemical shifts of a wide range of organic molecules in aqueous solution, including metabolites. Molecular motif-specific linear scaling parameters are reported for five different density functional theory (DFT) methods (B97-2/pcS-1, B97-2/pcS-2, B97-2/pcS-3, B3LYP/pcS-2, and BLYP/pcS-2), which were applied to a large set of 176 metabolite molecules. The chemical shift root-mean-square deviations (RMSD) for the best method, B97-2/pcS-3, are 1.93 and 0.154 ppm for 13C and 1H chemical shifts, respectively. Excellent results have been obtained for chemical shifts of methyl and aromatic 13C and 1H that are not directly bonded to a heteroatom (O, N, S, or P) with RMSD values of 1.15/0.079 and 1.31/0.118 ppm, respectively. This study not only demonstrates how NMR chemical shift in aqueous environment can be improved over the commonly used global linear scaling approach, but also allows for motif-specific error estimates, which are useful for an improved chemical shift-based verification of metabolite candidates of metabolomics samples containing unknown components.

In situ patterning of organic molecules in aqueous solutions using an inverted electron-beam lithography system

A method for in situ controlling the detachment and deposition of organic molecules such as sugars and biocompatible polymers in aqueous solutions by electron-beam (EB) scan is proposed and evaluated. It was demonstrated that EB irradiation could detach 2-methacryloyloxyethyl phosphorylcholine (MPC) polymers from a silicon nitride membrane. Moreover, organic molecules such as cationic polymers and sugars could be deposited on the membrane by EB irradiation. Spatial distributions of scattered electrons were numerically simulated, and acceleration voltage dependences of the detachment and deposition phenomena were experimentally measured. The simulations and experimental results suggest that the detachment of MPC polymers is mainly due to electrical effects of primary electrons, and that the deposition of organic molecules is mainly due to chemical reactions induced by primary electrons. In view of these findings, the proposed method can be applied to in situ and nanoscale patterning such as the fabrication of cell scaffolds.

Per-2,3-O-alkylated β-cyclodextrin duplexes connected with disulfide bonds

Per-2,3-di-O-methyl- and per-2,3-di-O-allyl-β-cyclodextrin duplexes held by two disulfide bonds between their primary faces have been prepared. Permethylation significantly increased the solubility of the cyclodextrin duplexes in a wide range of solvents from water to chlorinated hydrocarbons. Per-2,3-di-O-methylated duplexes are able to form inclusion complexes with organic molecules in aqueous solutions, yet the stability constants are lower by 4–5 orders of magnitude as compared to analogous non-alkylated β-cyclodextrin duplexes.

Influence of HCOO– on Calcite Growth from First-Principles

Organic molecules in aqueous solutions are good candidates in the inhibition of some biogenic crystal growth. The formic acid HCOOH is considered to investigate at an atomic level the interaction between the carboxyl functional group −COO– and the (1014) hydrated surface of calcium carbonate, CaCO3, in the form of calcite. Ab initio simulations based on the density functional theory are performed to study the adsorption of undissociated and dehydrogenated HCOOH in the presence of water. Relevant adsorption energies obtained for HCOO– + H2O on calcite predict that water is essential in the stabilization of the carboxyl group in its deprotonated form. The interfacial properties and the trend of adsorption energies for different coverages are given in detail. The dissociation barriers of HCOOH on hydrated calcite are evaluated with the climbing-image nudged elastic band (CI-NEB) method.

Assessing the suitability of the multilevel strategy for the conformational analysis of small ligands.

Predicting the conformational preferences of flexible compounds is a challenging problem in drug design, where the recognition between ligand and receptor is affected by the ability of the interacting partners to adopt a favorable conformation for the binding. To explore the conformational space of flexible ligands and to obtain the relative free energy of the conformation wells, we have recently reported a multilevel computational strategy that relies on the predominant-state approximation-where the conformational space is partitioned into distinct conformational wells-and combines a low-level method for sampling the conformational minima and high-level ab initio calculations for estimating their relative stability. In this study, we assess the performance of the multilevel strategy for predicting the conformational preferences of a series of structurally related phenylethylamines and streptomycin in aqueous solution. The charged nature of these compounds and the chemical complexity of streptomycin make them a challenging test for the multilevel approach. Furthermore, we explore the suitability of using a molecular mechanics approach as a source of approximate ensembles in the first stage of the multilevel strategy. The results support the reliability of the multilevel approach for obtaining an accurate conformational ensemble of small (bio)organic molecules in aqueous solution.