Hydrogen-bond Basicity Research Articles

Reduced estrogenic risks of a sunscreen additive: Theoretical design and evaluation of functionally improved salicylates

Salicylic esters (SEs), the widely used ultraviolet (UV) absorbers in sunscreen products, have been found to have health risks such as skin sensitization and estrogenic effects. This study aims to design SE substitutes that maintain high UV absorbance while reducing estrogenicity. Using molecular docking and Gaussian09 software for initial assessments and further application of a combination of two-dimensional and three-dimensional quantitative structure–activity relationships (2D-QSAR and 3D-QSAR, respectively) models, we designed 73 substitutes. The best-performing molecules, ethylhexyl salicylate (EHS)−5 and EHS-15, significantly reduced estrogenicity (44.54 % and 17.60 %, respectively) and enhanced UV absorbance (249.56 % and 46.94 %, respectively). Through screening for human health risks, we found that EHS-5 and EHS-15 were free from skin sensitivity and eye irritation and exhibited reduced skin permeability compared with EHS. Furthermore, the photolysis and synthetic pathways of EHS-5 and EHS-15 were deduced, demonstrating their good photodegradability and potential synthesizability. In addition, we analyzed the mechanisms underlying the changes in estrogenic effects and UV absorption properties. We identified covalent hydrogen bond basicity and acidity Propgen value for atomic molecular properties and the highest occupied molecular orbital eigenvalue as the main factors affecting the estrogenic effect and UV absorbance of SEs, respectively. This study focuses on the design and screening of SEs, exhibiting enhanced functionality, reduced health risks, and synthetic feasibility.

Evaluation of the Goss-modified solvation parameter model for the characterization of biphasic systems and descriptor assignments

The solvation parameter model uses six descriptors identified as excess molar refraction, E, dipolarity/polarizability, S, overall hydrogen-bond acidity, A, overall hydrogen-bond basicity, B, McGowan's characteristic volume, V, and the gas-liquid partition constant on hexadecane at 25 °C, L to model the distribution of neutral compounds in biphasic systems. Abraham's version of this model uses all six descriptors with two separate linear free energy relationship models for the transfer of compounds from a gas phase to a condensed phase and between condensed phases. Goss proposed a modification to this model that uses a single calibration model regardless of the physical state for each phase and five of the descriptors employed in Abraham's model (E descriptor is eliminated). The capability of Abraham's model and the Goss-modified model to characterize the contribution of intermolecular interaction to retention for gas and reversed-phase liquid chromatographic systems and distribution in liquid-liquid partition systems is evaluated using the WSU compound descriptor database. These more accurate values for the Abraham descriptors have not been utilized previously for the evaluation of the Goss-modified model and should be more capable of discerning subtle differences in model performance. It is shown that model quality defined by statistical parameters favors Abraham's model over the Goss-modified model with differences in model quality greater for systems in which Abraham's model indicates a significant contribution from electron lone pair interactions and for systems in which one phase is a solvent containing perfluoroalkyl substituents. There is a small systematic difference for the terms describing the combined contributions of cavity formation and dispersion interactions and for interactions of a dipole-type. The contribution of hydrogen-bonding interactions is virtually identical for the two models. The model intercepts are generally different and potentially assigned to a larger contribution from lack-of-fit for the Goss-modified model. Although the Abraham model descriptors have been routinely employed for applications using the Goss-modified model the possibility that Goss-model specific descriptors should be employed was evaluated. Using the Solver method and Goss-model specific calibration models for chromatographic and liquid-liquid partition systems a new set of Goss-specific descriptors was calculated for 28 varied compounds. These descriptors show good statistical agreement with the Abraham descriptor values with an average deviation of 0.009, -0.003, -0.004, and -0.023, respectively, for the S, A, B, and L descriptors, corresponding to a relative absolute deviation in percent of 2.2 %, 3.9 %, 4.3 %, and 1.2 %, respectively.

Guidelines for descriptor assignments for the solvation parameter model by separation techniques

The solvation parameter model uses six compound descriptors to model equilibrium properties in biphasic systems formally defined as excess molar refraction, E, dipolarity/polarizability, S, overall hydrogen-bond acidity, A, overall hydrogen-bond basicity, B, McGowan's characteristic volume, V, and the gas-liquid partition constant on hexadecane at 25 °C, L. The V descriptor can be assigned from structure and the E descriptor for compounds liquid at 20 °C can be calculated from its refractive index and characteristic volume. The E descriptor for compounds solid at 20 °C and the S, A, B, and L descriptors are assigned from experimental properties traditionally obtained by chromatographic, liquid-liquid partition, and solubility measurements. Here I report an efficient experimental design using the Solver method for the accurate assignment of descriptors for neutral compounds that simultaneously minimizes laboratory resources. This multi-technique approach requires 3 retention factor measurements in a 60 °C temperature range per compound on four columns by gas chromatography, 3 retention factor measurements in a 30 % (v/v) acetonitrile composition range per compound on two columns by reversed-phase liquid chromatography, and eight partition constant measurements by liquid-liquid partition in totally organic and aqueous biphasic systems for a total of 26 experimental measurements. The accuracy of the descriptor assignments was validated by comparison with the values in the Wayne State University (WSU) descriptor database taken as the best estimate of the true descriptor values. The E, S, A, B and L descriptors were assigned simultaneously by the Solver method using the above approach without significant bias and with an average absolute deviation (AAD) of 0.054, 0.018, 0.015, 0.013, and 0.040, respectively, compared with the WSU database values, corresponding to a relative absolute average deviation in percent (RAAD) of 7.2, 1.9, 3.6, 5.1, and 0.84 %, respectively, for 32 varied compounds. This streamlined approach represents a significant improvement on earlier single-technique approaches used as the starting point for the development of the multi-technique approach. For compounds of variable hydrogen-bond basicity modifications to the multi-technique approach were implemented while maintaining the same number of experimental measurements. Acceptable descriptor assignments for B/B° were obtained for compounds liquid at 20 °C for which the E descriptor was available by calculation. For solid compounds at 20 °C the E and B/B° descriptors are restricted to qualitative application where approximate values may be acceptable.

Deep eutectic solvent (TMAH·5H2O/Urea) with low viscosity for cellulose dissolution at room temperature

A deep eutectic solvent (DES) formulated with tetramethylammonium hydroxide pentahydrate /urea (TMAH·5H2O/Urea) was designed for the first time to dissolve cellulose at room temperature. The optimized system, characterized by a 1:3 M ratio, demonstrates the capability to dissolve approximately 7.5 wt% cellulose, boasting a high degree of polymerization (DP = 526). Notably, both the pure DES and 4.0 wt% cellulose/TMAH·5H2O/Urea mixtures manifests low viscosity, establishing its potential as an effective spinning aid in fiber manufacturing. The structural analyses shows that the cellulose crystal type shifts from type I to type II form, accompanied by a reduction in both crystallinity and DP. A pivotal aspect of this research involves determining Kamlet-Taft parameters for TMAH·5H2O/Urea-DES with different molar ratios. The results reveal these solvate DESs exhibit the high hydrogen bond basicity, which enables them to easily form hydrogen bonds with hydroxyl groups of cellulose and demonstrate good cellulose solubility. In conclusion, this solvent system presents notable advantages, including straightforward synthesis procedures, low viscosity, and well cellulose solubility, paving the way for new approaches and techniques in cellulose utilization.

Solvent Acidity and Basicity Scales: Analysis of Catalan’s SB and SA Scales and Gutmann’s Acceptor Number and Comparison with Kamlet and Taft’s β and α Solvent Scales, Gutmann’s Donor Number and Abraham’s B and A Solute Scales

The use of experimental parameters to quantify solvent properties, for example in linear free energy relationships, is well established and several scales of solvent acidity, basicity and polarity/polarizability have been developed. The success of this approach raises questions of which molecular properties contribute to particular solvent parameters and whether these contributions are found in all parameters representing a particular solvent property. In the present study, Catalan’s hydrogen bond basicity and acidity parameters, SB and SA, and Gutmann’s acceptor number, AN, a measure of a solvent’s Lewis acidity, are correlated with molecular properties derived from computational chemistry. The results are compared with the results of similar correlations with Kamlet and Taft’s β and α Solvent Scales, Gutmann’s donor number DN) and Abraham’s B and A solute scales. The results show that measures of solvent basicity, SB, β and DN all correlate strongly with the partial charge on the most negative atom in the solvent molecule and the energy of the donor orbital and, in all cases, the parameter values for hydrogen-bonded solvents are anomalous. Abraham’s B, a measure of solute hydrogen basicity, depends only on the partial charge on the most negative atom and there is no anomaly in the values for solutes that, in the pure state, form hydrogen-bonded liquids. Similarly, all measures of solvent acidity, SA, α and AN, and Abraham’s A, a measure of solute hydrogen bond acidity, depend on the partial charge on the most positive hydrogen on the molecule.

The Tautomeric State of N4-Hydroxycytidine within Base-Paired RNA.

Antiviral nucleoside analogues (e.g., Molnupiravir, Remdesivir) played key roles in the treatment of COVID-19 by targeting SARS-CoV-2 RNA-dependent RNA polymerase (RdRp). The nucleoside of Molnupiravir, N4-hydroxycytidine (NHC), exists in two tautomeric forms that pair either with G or A within the RdRp active site, causing an accumulation of viral RNA mutations during replication. Detailed insights into the tautomeric states within base pairs and the structural influence of NHC in RNA are still missing. In this study, we investigate the properties of NHC:G and NHC:A base pairs in a self-complementary RNA duplex by UV thermal melting and NMR spectroscopy using atom-specifically 15N-labeled versions of NHC that were incorporated into oligonucleotides by solid-phase synthesis. NMR analysis revealed that NHC forms a Watson-Crick base pair with G via its amino form, whereas two equally populated conformations were detected for the NHC:A base pair: a weakly hydrogen-bonded Watson-Crick base pair with NHC in the imino form and another conformation with A shifted toward the minor groove. Moreover, we found a variable influence of NHC:G and NHC:A base pairs on the neighboring duplex environment. This study provides conclusive experimental evidence for the existence of two tautomeric forms of NHC within RNA base pairs.

Theoretical models of solubility for organic solvents. A conceptual density functional theory approach

We present a simple semi-empirical model for solubility in organic solvents, based on the conceptual density functional theory (CDFT) and inspired on the well-known empirical linear solvation energy relationships (LSER) proposed by Kamlet and Taft, where a multiparametric correlation between solubility and empirical descriptors including the hydrogen bond acidity (HBA) and basicity (HBB) plus an additional term describing the dipole polarizability of the solvents was presented. Herein, we set up an analogue model that describes HBA, HBB and dipole polarizability with electronic descriptors derived from the conceptual density functional theory. The main relevant results are as follows: (i) as expected, HBA and HBB properties are not absolute but regional properties, thereby suggesting that any solvent can display both properties with different weights (bifunctional solvents); (ii) while HBA can nicely be represented by a regional electrophilicity index, the HBB property can be accounted for by a regional nucleophilicity. The dipole polarizability is consistently represented by the global softness of the solvent molecule; (iii) the regionalization of these properties is achieved by defining electrophilic and nucleophilic basins within a given solvent molecule by using the electrophilic and nucleophilic Fukui Functions integrated within these basins. The resulting model is validated against the experimental solubility of vanillin and hesperidin in different organic solvents. Further perspectives of the present study should be of special interest in theoretical studies concerning ionic liquids and deep eutectic solvents.

Assessment of liquid-liquid partition for the assignment of descriptors for the solvation parameter model

The solvation parameter model uses five system independent descriptors to characterize compound properties defined as excess molar refraction, E, dipolarity/polarizability, S, hydrogen-bond acidity, A, hydrogen-bond basicity, B, and McGowan's characteristic volume, V, to model transfer properties between condensed phases. The V descriptor is assigned from structure. For compounds liquid at 20 °C the E descriptor can be assigned from the characteristic volume and its refractive index. The E descriptor for compounds solid at 20 °C and the S, A, and B descriptors are experimental properties traditionally assigned from chromatographic, liquid-liquid partition, and solubility measurements. In this report liquid-liquid partition constants in totally organic and aqueous biphasic systems are evaluated as a standalone technique for descriptor assignments. Using six totally organic biphasic systems the S, A, and B descriptors were assigned with an average absolute deviation (AAD) of about 0.04, 0.03, and 0.04, respectively, compared with the best estimate of the true descriptor values for 65 compounds. The E descriptor for compounds solid at 20 °C can only be estimated with an AAD of approximately 0.1. For six aqueous biphasic systems the B descriptor is assigned with a lower AAD of 0.028 and higher AAD of 0.08 and 0.05 for the S and A descriptors, respectively, than for the totally organic biphasic systems for compounds with a reliable value for the E descriptor. The preferred system for descriptor assignments utilizes both totally organic biphasic systems (heptane-1,1,1-trifluoroethanol, isopentyl ether-propylene carbonate, isopentyl ether-ethanolamine, heptane-ethylene glycol, heptane-formamide, and 1,2-dichloroethane-ethylene glycol) and aqueous biphasic systems (octanol-water, cyclohexane-water) with the possible substitution of some systems with alternative systems of similar selectivity. For 55 varied compounds this combination of eight organic and aqueous biphasic systems resulted in an AAD of approximately 0.03, 0.02, and 0.02 for the S, A, and B descriptors compared to the best estimate of the true descriptor value. For 30 compounds solid at 20 °C the AAD for the E descriptor of 0.11 is poorly assigned. The relative average absolute deviation in percent (RAAD) corresponds to 9.7 %, 3.1 %. 4.0 % and 8.3 % for E, S, A, and B, respectively, for the eight biphasic systems. Liquid-liquid partition is compared to reversed-phase liquid and gas chromatography as a standalone technique for descriptor assignments.

Determination of solvation parameter model compound descriptors by gas chromatography

The solvation parameter model uses five system independent descriptors to characterize compound properties defined as excess molar refraction, E, dipolarity/polarizability, S, hydrogen-bond acidity, A, hydrogen-bond basicity, B, and the gas-liquid partition constant at 25 °C on n-hexadecane, L, to model transfer properties in gas-condensed phase biphasic systems. The E descriptor for compounds liquid at 20 °C is available by calculation using a refractive index value while E for solid compounds at 20 °C and the S, A, B, and L descriptors are determined by experiment. As a single-technique approach, it is shown that with up to 20 retention factor measurements on four columns comprising a poly(siloxane) containing methyloctyl or dimethyldiphenylsiloxane monomers (SPB-Octyl or HP-5), a poly(siloxane) containing methyltrifluoropropylsiloxane monomers (Rtx-OPP or DB-210), a poly(siloxane) containing bis(cyanopropylsiloxane) monomers (HP-88 or SGE BPX-90), and a poly(ethylene glycol) stationary phase (DB-WAXetr or HP-INNOWAX) are suitable for assigning the S, A, and L descriptors. Using the descriptors in the updated WSU compound descriptor database as target values the average absolute error in the descriptor assignments for 52 varied compounds in the temperature range 60–140 °C was 0.072 for E, 0.016 for S, 0.008 for A, and 0.022 for L corresponding to 30 %, 3.5 %, and 0.6 % as a relative average absolute error for E, S, and L, respectively. For the higher temperature range of 160–240 °C and 34 varied compounds that are liquid at 20 °C the average absolute error for the S, A and L descriptors was 0.026, 0.020, and 0.031, respectively, with the largest relative average absolute error for S of 3.2 % (< 1 % for the L descriptor). For 35 varied compounds that are solid at 20 °C the relative absolute error for the E, S, A, and L descriptors in the higher temperature range was 0.068, 0.035, 0.020, and 0.020, respectively, with a relative average absolute error for E (6.5 %), S (3.5 %) and L (0.88 %). The S, A, and L descriptor can be accurately assigned on the four-column system over a wide temperature range. The E descriptor for solid compounds at 20 °C exhibits greater variability than desirable. The B descriptor cannot be assigned by the four-column system, which lack hydrogen-bond acid functional groups, and is only poorly assigned on the weak hydrogen-bond acid ionic liquid column SLB-IL100.

Determination of the hydrogen-bond basicity descriptor by reversed-phase liquid chromatography

Except for alkanes, most organic compounds are hydrogen-bond bases. The B° descriptor of the solvation parameter model provides a convenient measure of the effective (or summation) hydrogen-bond basicity of organic compounds. A fast and convenient method to assign the B° descriptor is required to support studies of hydrogen-bonding in separation systems. A two-column system with acetonitrile-water mobile phase compositions and the measurement of up to eleven isocratic retention factors is proposed for this purpose. Several reversed-phase column chemistries and mobile phases were evaluated with the two-column system consisting of a pentafluorophenylpropylsiloxane-bonded and octadecylsiloxane-bonded silica columns recommended for this purpose. To assess the accuracy of the method values for B° were taken from the Wayne State University (WSU) compound descriptor database, which were assigned using conventional multi-technique methods and large datasets. The two-column systems provided an unbiased assignment of B° with an average deviation of 0.008 and an average absolute deviation of 0.021 compared with the target value for 55 varied compounds. The two-column system is unsuitable for assigning the other descriptors used in the solvation parameter model and results in erroneous assignments of B° for nitrogen-containing compounds capable of electrostatic interactions on silica-based reversed-phase columns.

Contiguous Silver(I)-Mediated Base Pairs of Imidazophenanthroline and Canonical Nucleobases in DNA Duplexes: Formation of Classical Duplexes versus Homodimer Formation.

Metal-mediated base pairs represent a topical alternative to canonical hydrogen-bonded base pairs. In this context, the ligand 1H-imidazo[4,5-f][1,10]phenanthroline (P) was introduced as an artificial nucleobase in a glycol nucleic acid-based nucleoside analogue into a DNA oligonucleotide in a way that the oligonucleotide contains a central block of six contiguous P residues. The ability to engage in Ag+-mediated base pairing was evaluated with respect to the four canonical nucleosides in positions complementary to P. Highly stabilizing Ag+-mediated base pairs were formed with cytosine and guanine (i.e., P-Ag+-C and P-Ag+-G base pairs), whereas the analogous base pairs with thymine and adenine were much less stable and hence formed incompletely. Surprisingly, the intermediate formation of a homodimeric duplex of the P-containing oligonucleotide was observed in all cases, albeit to a different extent. The homodimer is composed of P-Ag+-P base pairs and 18 overhanging mismatched canonical nucleobases. It demonstrates the obstacles present when designing metal-mediated base pairs as metal complexation may take place irrespective of the surrounding natural base pairs. Homodimer formation was found to be particularly prominent when the designated metal-mediated base pairs are of low stability, suggesting that homodimers and regular duplexes are formed in a competing manner.

Machine learning for skin permeability prediction: random forest and XG boost regression

Background: Machine learning algorithms that can quickly and easily estimate skin permeability (Kp) are increasingly being used in drug delivery research. The linear free energy relationship (LFER) developed by Abraham is a practical technique for predicting Kp. The permeability coefficients and Abraham solute descriptor values for 175 organic compounds have been documented in the scientific literature. Purpose: The purpose of this project was to use a publicly available dataset to make skin permeability predictions using the random forest and XBoost regression techniques. Methods: We employed Pandas-based methods in JupyterLab to predict permeability coefficient (Kp) from solute descriptors (excess molar refraction [E], combined dipolarity/polarizability [S], overall solute hydrogen bond acidity and basicity [A and B], and the McGowan's characteristic molecular volume [V]). Results: The random forest and XG Boost regression models established statistically significant association between the descriptors and the skin permeability coefficient.

A polemic on the use of reversed-phase liquid chromatography to determine descriptors for the solvation parameter model

Revised descriptors for 74 varied compounds recommended for the characterization of reversed-phase silica columns using the solvation parameter model are assigned by the Solver method from experimental retention factors for calibrated gas-liquid and reversed-phase liquid chromatographic (RPLC) and biphasic liquid-liquid partition systems. These descriptors are taken as the best estimate of the true descriptor values and used to evaluate several RPLC systems as a single-technique approach for descriptor assignments. Various combinations of isocratic single column and multiple mobile phase compositions, multiple columns with a single mobile phase composition, and multiple columns and multiple mobile phase compositions are evaluated. A multiple column (Discovery HS C18 and HS F5, Fluophase-RP, and XBridge Shield RP18, Phenyl, and C18) with acetonitrile- and methanol-water mobile phases provided the best results with an absolute average deviation (AAD) of 0.043 for the electron lone pair interaction descriptor E, 0.047 for the dipole-type interaction descriptor S, 0.020 for the hydrogen-bond acid descriptor A, and 0.010 for the hydrogen-bond base descriptor B° for 46 varied compounds. These values compare favorably with the larger all columns and mobile phase composition RPLC dataset with the best estimate of the true descriptors, or all data set, with AAD = 0.026 for E, 0.044 for S, 0.027 for A, and 0.011 for B° for 74 varied compounds. The preferred RPLC systems for descriptor assignments contain columns identified as belonging to different selectivity groups that maximize the relative magnitude of the dipole-type contribution, s system constant, hydrogen-bond basicity, a system constant, and electron lone pair interactions, e system constant. RPLC systems are well suited to assigning the B° descriptor and, with proper system selection, the A and S descriptors. The E descriptor for compounds unavailable by calculation is more problematic and a few extreme values with an AAD > ± 0.1 were observed and can affect the reliability of the S descriptor assignments for these compounds. The likelihood of poor descriptor assignments using the Solver method can be identified by evaluating descriptor wells.

Cooperativity and topological hydrogen bonding in aromatic diol complexes

AbstractComplexes of three aromatic diols, catechol, naphthalene‐1,8‐diol, and fluorene‐4,5‐diol, with a series of hydrogen bond acceptors (HBAs) that have oxygen, nitrogen, and sulfur acceptor atoms, have been studied by density functional theory (DFT) at the B3LYP/6‐311+G(d,p) level. Binding energies, geometries, infrared spectroscopic (IR) frequencies, nuclear magnetic resonance (NMR) shifts, and measures of the electron density distribution from the Quantum Theory of Atoms in Molecules (QTAIM) are evaluated and compared with data for the corresponding monohydroxy compounds (monols), phenol, naphth‐1‐ol, and fluorene‐4‐ol, in order to assess the importance of cooperativity between intramolecular and intermolecular hydrogen bonding. All measures for all complexes show positive cooperativity whereby both the intermolecular and intramolecular hydrogen bonds are strengthened upon complexation. Cooperativity is weak for catechol and strong for the other two diols and, for all diols, increases with the hydrogen bond basicity of the acceptor. Correlations of IR and NMR metrics against binding energies for a single HBA and all six monols and diols are excellent, but attempts to correlate the same metrics for all HBAs and a single donor are frustrated by differences in intermolecular hydrogen bonding, depending notably on the identity of the acceptor atom in the HBA. Atom–atom interaction energies, calculated by the Interacting Quantum Atoms approach, are used to discuss the covalency of both types of hydrogen bond.

Further Understanding the Roles of Solvent, Brønsted Acids, and Hydrogen Bonding in Iron Porphyrin-Mediated Carbon Dioxide Reduction.

Improving our understanding of how molecules and materials mediate the electrochemical reduction of carbon dioxide (CO2) to upgraded products is of great interest as a means to address climate change. A leading class of molecules that can facilitate the electrochemical conversion of CO2 to carbon monoxide (CO) is iron porphyrins. These molecules can have high rate constants for CO2-to-CO conversion; they are robust, and they rely on abundant and inexpensive synthetic building blocks. Important foundational work has been conducted using chloroiron 5,10,15,20-tetraphenylporphyrin (FeTPPCl) in N,N-dimethylformamide (DMF) solvent. A related and recent report points out that the corresponding perchlorate complex, FeTPPClO4, can have superior function due to its solubility in other organic solvents. However, the importance of hydrogen bonding and solvent effects was not discussed. Herein, we present a detailed kinetic study of the triflate (CF3SO3-) complex of FeTPP in DMF and in MeCN using a range of phenol Brønsted acid additives. We also detected the formation of Fe(III)TPP-phenolate complexes using cyclic voltammetry experiments. Importantly, our new analysis of apparent rate constants with different added phenols allows for a modification to the established mechanistic model for CO2-to-CO conversion. Critically, our improved model accounts for hydrogen bonding and solvent effects by using simple hydrogen bond acidity and basicity descriptors. We use this augmented model to rationalize function in other reported porphyrin systems and to make predictions about operational conditions that can enhance the CO2 reduction chemistry.

The effect of the assigned descriptors for phthalate esters on the characterization of their separation properties using the solvation parameter model

Revised descriptors are determined for fifteen phthalate esters for use in the solvation parameter model and form part of the Wayne State University (WSU) compound descriptor database. For thirteen phthalate esters a comparison is made with the same compounds in the Abraham descriptor database. Gas chromatographic retention factors on poly(methyloctylsiloxane), SPB-Octyl, and poly(cyanopropylphenyldimethylsiloxane), DB-225, stationary phases are used to facilitate an assessment of the contribution of cavity formation and dispersion interactions, L descriptor, and dipole-type interactions, S descriptor, to the experimental retention factors (log k) for the phthalate esters with minimum interference from competing intermolecular interactions. The results indicate a systematic overprediction of the cavity and dispersion interaction term and underprediction of dipole-type interactions for the Abraham descriptors compared with the WSU descriptors for the phthalate esters. The average absolute deviation (AAD) for 13 phthalate esters on SPB-Octyl is 0.039 (WSU descriptors) compared with 0.252 (Abraham descriptors) and for 9 phthalate esters on DB-225 0.030 (WSU descriptors) compared with 0.167 (Abraham descriptors). The results for dipole-type interactions are confirmed and extended to include the hydrogen-bond basicity of the phthalate esters, B descriptor, by evaluation of partition constants in aqueous biphasic systems and the n-heptane-2,2,2-trifluoroethanol biphasic system. Differences in the contribution of the hydrogen-bond basicity of the phthalate esters to the experimental partition constants are largely random with respect to database selection but important for the accurate prediction of the partition constants. The AAD for the partition constant for 15 phthalate esters is 0.063 (WSU descriptors) compared with 0.320 (Abraham descriptors) for the heptane-2,2,2-trifluoroethanol biphasic system and 0.13 (WSU descriptors) compared with 0.25 (Abraham descriptors) for 9 phthalate esters in the octanol-water biphasic system. The WSU descriptors for the phthalate esters exhibit a better fit with the experimental data for separation systems and are free of the extreme values predicted for the Abraham descriptors for several phthalate esters.

Efficient Cellulose Dissolution and Film Formation Enabled by Superbase Amino Acid Ionic Liquids.

Cellulose is a promising feedstock for the production of sustainable materials. To fully utilize its potential, exploring efficient cellulose solvents is a paramount prerequisite. In this study, ten superbase amino acid ionic liquids (SAAILs) are synthesized using 1,5-diazabicyclo[4.3.0]non-5-ene (DBN) and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) with different amino acid anions via a simple neutralization method. The properties of these SAAILs, such as viscosity and glass transition temperature, varied with their cation and anion structures. The ability of the SAAILs to dissolve cellulose is related to their Kamlet-Taft parameters, particularly hydrogen bond basicity (β). The main driving force for cellulose dissolution in SAAILs is thought to be hydrogen bonding interactions between SAAILs and cellulose hydroxyl groups. Four SAAILs composed of DBN or DBU cations and proline, or aspartic acid anions are identified as promising solvents for preparing regenerated cellulose films (RCFs). The RCF prepared from [DBN]Proline(Pro) showed a favorable combination of high tensile strength (76.9MPa), high Young's modulus (5201.2MPa), good transparency (≈70% at 550nm), and smooth surface morphology. These halogen- and metal-free SAAILs show the potential to provide a new avenue for cellulose processing.

Reactions

PEOPLE Reactions ShareShare onFacebookTwitterWechatLinked InRedditEmail C&EN, 2023, 101 (17), p 3May 29, 2023Cite this:C&EN 101, 17, 3Letters to the editorRecognizing more contributors to DNA discoveryIn Wikipedia, there are 21 scientists listed who made significant contributions to determining the structure of DNA. In recent decades the focus has been on the contributions of only 3 of those individuals, to the exclusion of others (C&EN, May 1, 2023, page 6). For example, a recent book on paleogenetics attributes this discovery solely to James Watson and Francis Crick using Rosalind Franklin’s data. While Watson and Crick did derive a complete model for the structure of DNA, they were greatly assisted by information from multiple sources.Florence Bell obtained the first diffraction image of DNA in 1938 while working with William Astbury. Their publication described DNA as being like a “pile of pennies” with a periodicity of 3.3–3.4 Å along the axis.The group at King’s College London consisted of John Randall (head), Maurice Wilkins (assistant head), Alexander Stokes (lecturer), Franklin (postdoctoral researcher), Herbert Wilson (postdoctoral researcher), and Raymond Gosling (PhD student). Wilkins and Gosling obtained an X-ray diffraction image of the A-form of DNA in 1950; Stokes performed theoretical calculations for the expected diffraction pattern of a helical structure and compared it with the diffraction image to confirm that the structure was indeed helical (with C2 symmetry). Stokes was therefore the first person to identify the helicity associated with the backbone of DNA. Subsequent work by Franklin and Gosling in 1951–52 provided a much more detailed analysis of the sodium deoxyribophosphate backbone of DNA.Information on the purine-pyrimidine hydrogen-bonded base pairs, which contain the coded genetic information in DNA, came from Erwin Chargaff’s studies of the ratios of the specific bases in a range of DNA samples from different sources; currently these results are formulated as Chargaff’s rules (published in 1952).Jerry Donohue was a visiting scientist at the University of Cambridge when Watson and Crick were attempting to build a purine-pyrimidine dimer model. Donohue had studied hydrogen bonding in organic crystals at the California Institute of Technology (PhD under Linus Pauling) and helped significantly in the development of an accurate dimer model.Unravelling the Double Helix: The Lost Heroes of DNA, by Gareth Williams, gives a nicely detailed chronology of the contributions of the many scientists involved in this discovery.Ralph A. WhitneyKingston, OntarioThe supramolecular factor in AIThe use of artificial intelligence is now receiving considerable attention by the pharmaceutical industry as an alternative to classic approaches toward drug design. Here, machines that mimic human intelligence are being asked to rapidly identify new drug candidates. One significant factor that I believe has been overlooked by AI, and by virtually all other drug design approaches, is the supramolecular factor. Specifically, what I’m referring to is the difference in the biological action of agents that function as single molecules versus ones that function as a collection of these molecules—that is, as aggregates.To illustrate what I’m talking about, consider the known properties of amphotericin B. This drug has served as the gold standard for treating life-threatening fungal infections for the past 50 years. It has also earned the reputation of being one of the most toxic drugs used in modern medicine. Indeed, physicians often refer to amphotericin B as “amphoterrible.” In laboratory studies by Jacques Bolard and coworkers in Paris, it has been shown that single molecules of amphotericin B are highly selective in destroying fungal cells over red blood cells, while aggregates of this drug readily destroy both cell types. This fact by itself can explain why amphotericin B is so toxic when used therapeutically. Specifically, aggregates of this agent may be making a major contribution to its biological action. Consistent with this explanation, we have found that synthetic derivatives of amphotericin B that exhibit a reduced tendency to aggregate are more selective in destroying fungal cells and are less toxic, according to laboratory and animal studies. The fact that similar behavior has also been reported for certain antibacterial agents—in which single molecules favor the destruction of bacterial cells over red blood cells while aggregates readily destroy both types of cells—implies that this dichotomy is likely to reflect a general and heretofore unrecognized phenomenon. In principle, this could have direct relevance not only for the design of new antibiotics that are sorely needed but also for the design of other classes of drugs, such as novel anticancer agents. If this proves to be the case, then improvements in drug design should be possible using databases and drug design principles that minimize the tendency of biologically active agents to aggregate—that is, by taking the supramolecular factor into account.Steven L. RegenBethlehem, Pennsylvania CorrectionMay 15/22, 2023, page 32: The Talented 12 profile of Stacy Malaker has an incorrect photo credit. The photographer is Andrew Cortellini, not courtesy of Susannah Banziger.

Physisorption behaviors of deoxyribonucleic acid nucleobases and base pairs on bismuthene from theoretical insights

In this article, we conduct a density functional theory (DFT) investigation to reveal the adsorption characteristics of single deoxyribonucleic acid (DNA) nucleobases and hydrogen-bonded base pairs on monolayer bismuthene. The calculation results show that adenine (A), cytosine (C), guanine (G), thymine (T) interact with bismuthene in the following strength order: G > C > A > T. The magnitude of the adsorption energy is found to be 0.83 eV, 0.69 eV, 0.65 eV, 0.59 eV, respectively. These distinguishable energy levels make bismuthene a potential surface for selective detection of the four bases. During the adsorption processes, A, G, and T take charge from the adsorbent, whereas C provides charge to the adsorbent. Through electronic properties analyses, we demonstrate their physisorption essence. The key role of single oxygen atom in stronger interactions between bismuthene and C/G is also concluded. The theoretical desorption time of adsorbed G and T at 398 K are 3.21 × 10−2 s and 2.94 × 10−5 s. In addition, A-T and C-G pairs can be adsorbed on bismuthene with an adsorption energy of − 1.20 eV and − 1.26 eV. According to the detailed parameters of the pairs before and after adsorption, the hydrogen bonds between complementary bases can remain stable under the effect of bismuthene.

Complementary base pair interactions between different rare tautomers of the second-generation artificial genetic alphabets

The functionality of a semisynthetic DNA in the biological environment will depend on the base pair nature of its complementary base pairs. To understand this, base pair interactions between complementary bases of recently proposed eight second-generation artificial nucleobases are studied herein by considering their rare tautomeric conformations and a dispersion-corrected density functional theoretic method. It is found that the binding energies of two hydrogen-bonded complementary base pairs are more negative than those of the three hydrogen-bonded base pairs. However, as the former base pairs are endothermic, the semisynthetic duplex DNA would involve the latter base pairs.