ABSTRACT A hemicarcerand first reported by Quan and Cram in 1991 was prepared and characterized by X‐ray crystallography. It incorporates CoCp 2 + PF 6 − with an equilibrium constant of ~220 M −1 at 120°C and apparently is indefinitely stable at room temperature. This potential weakly coordinating cation's structure was also determined by X‐ray analysis, and the cation is located on the inside and the counteranion on the outside of the cage through one of its four potential openings. Computations model these results and suggest that the imine linker needs to be modified to reduce the electrostatic attraction of the oppositely charged ions by physically separating them further.
The advancement of molecular ferroelectric materials for digital information storage requires systems that exhibit predictable polarization switching under ambient conditions. Recently, room‐temperature polarization switching was observed from a single crystal of the nitrogen‐centered triangulene, azangulene, revealing nitrogen inversion as a promising mechanism by which to achieve ferroelectricity. While an exciting addition to the library of organic molecular ferroelectrics, azangulene is limited by an irreversible single‐crystal‐to‐single‐crystal phase transition that kinetically traps the system in a nonpolar and nonferroelectric molecular conformation, necessitating subtle tuning of the conformational energy landscape to preserve room‐temperature polarization switching, while eliminating (destabilizing) nonpolar conformers. Two triangulene design principles emerged from computational studies of azangulene derivatives focused on bridging atom selection and aryl functionalization. This work seeks to experimentally validate these computational design principles in the solid state, while identifying additional noteworthy factors that may impact the translatability of computational design principles to experimental solid‐state systems. Using two model systems, nitrogen‐containing 6/6/6 linear tricycles and bridged triphenylamine derivatives, four factors affecting nitrogen inversion are experimentally explored in the solid state: (i) size mismatch between the central and bridging atoms in triangulenes; (ii) the role of aryl functionalization on the central nitrogen and bridging atom geometries; (iii) (de)coupling between molecular bowl and nitrogen atom inversion; and (iv) the relative magnitude of intra‐ versus intermolecular factors on solid‐state bowl conformation. From this work, we offer actionable strategies to tune nitrogen inversion in azangulene‐based ferroelectric materials.
Theoretical research on the intermolecular interactions (crosstalk) between catecholamine neurotransmitters (CATs) and neurologically active ions (NAIs) such as , and has been performed using the density functional B3LYP method with 6‐311++G (d, p)+SDD basis set in aqueous phase. Complexation energy analysis predicts that average interaction energy between CATs and ion in aqueous phase is ~−22.9 , which is ~3 times higher (i.e., stronger) than the reported experimental interaction energy between dopamine and dopamine transporter (−7.4 ). Interaction with anion () is weaker than cations (/). NBO charge analysis predicted that and interact with donor atoms (N or O) and cloud of the benzene ring in CATs whereas ion interacts with the acidic hydrogen of –OH/‐CH groups by the formation of H‐bonds, which is also supported with structural analysis of complexes. Fukui function analysis indicated that chemical reactivity as well as antioxidant activity of CATs is altered because of the interactions with NAIs. All these analyses suggested that molecular crosstalk between CATs and NAIs might perturb the interactions between CATs and receptors during neurotransmission as well as CATs and transporters during reuptake process.
The photochemistry of ethyl 2‐diazo‐3,3,3‐trifluoropropanoate (CF3CN2CO2Et) was studied in solution at ambient temperature with femtosecond (fs) time‐resolved infrared (IR) spectroscopy. Experimental results are interpreted with the aid of quantum mechanical calculations. The upper singlet excited state Sn of CF3CN2CO2Et decays by three processes: internal conversion to the ground state, fragmentation to the singlet carbene, and diazirine formation. The singlet carbene then subsequently decays to triplet carbene or reacts with the solvent. In methanol‐D (MeOD), typically a proficient scavenger of singlet carbenes, the carbene‐alcohol ylide was produced. The analogous CH3CN‐ylide of the singlet carbene is produced when the photolysis is performed in acetonitrile, while in CHCl3, the C–Cl insertion product was detected.
Xanthones are a prominent class of natural products with diverse biological activities, often modulated by their photophysical properties. Here, we present a theoretical investigation of the photoemission of five Amazonian xanthones (XAN1–5) in aqueous environment using Density Functional Theory (DFT) and Time‐Dependent DFT (TD‐DFT), combined with QTAIM and Voronoi Deformation Density (VDD) analyses. Our results show that all derivatives form stable intramolecular O–H···O hydrogen bonds in the ground state, with interaction energies ranging from −10.3 to −11.8 kcal/mol. Excitation leads to a direct ESIPT transformation only for XAN 2, XAN 3, and XAN 4, whereas XAN 1 and XAN 5 remain stabilized in the enolic form during the first excited‐state relaxation. QTAIM topological parameters reveal that while ground‐state H‐bond strength is relatively similar across the series, VDD identifies a threshold of local charge polarization required for the proton mobility. This indicates that while ground‐state H‐bonding arrangement and local charge polarization are essential, they are not sufficient to induce ESIPT. Our analysis suggest that this process is governed by the specific electronic redistribution in the lowest excited state, which must enhance the acceptor basicity to trigger proton transfer. These findings provide molecular‐level theoretical insights into the photophysics of Amazonian xanthones and offer a guide for the design of new photoactive antioxidant compounds.
Sulfondiimines are an emerging sulfur(VI) functional group with increasing use in synthesis and medicinal chemistry, yet their photochemical behavior has remained largely unexplored. In this work, the photochemistry of a series of six N‐substituted, N′‐tosyl diphenyl sulfondiimines was analyzed. Upon direct UV irradiation, five derivatives underwent efficient photodenitrenation in a consistent, stepwise order: extrusion of the N‐substituent nitrene followed by release of the N‐tosyl nitrene from the corresponding sulfilimine. This sequential nitrene release is a rare behavior that has not been observed previously. Quantum yield measurements reveal strong substituent dependence, with aryl substituents exhibiting substantially higher photochemical efficiency (0.22–0.31) than alkyl substituents (~0.1), whereas the NH‐substituted compound remained photoinert under our conditions. Product profiles and trapping experiments support the S–N cleavage in sulfondiimines to release the nitrene through a singlet manifold. Photosensitization experiments revealed the triplet manifold is dissociative as well, albeit with a greater number of side reactions. Quantum chemical calculations further supported this mechanism by relating the release order to relative S–N bond strengths and identifying a dissociative excited state along the S–N coordinate.
Hydropersulfides (RSSH) are emerging reactive sulfur species with distinctive chemical properties. Compared with conventional thiols and disulfides, RSSH exhibit enhanced acidity, nucleophilicity, reducing capabilities, and electrophilicity, enabling unique redox and sulfur transfer activity under physiological conditions. Their intrinsic instability and high reactivity have limited direct mechanistic studies. Over the past decade, a range of small‐molecule RSSH donors have been developed to probe RSSH chemistry and biology. In this review, we survey different strategies for RSSH generation, including direct‐release donors and self‐immolative platforms, the latter of which exploit elimination cascades or cyclization‐triggered mechanisms to achieve controlled RSSH release. We discuss trigger‐specific activation, structure–activity relationships, and factors governing RSSH release kinetics. We also highlight emerging biological applications of RSSH donors, where studies have explored their potential to modulate oxidative and nitrosative stress, maintain cellular redox balance, and mitigate tissue injury in cardiac, hepatic, and neuronal models. These investigations underscore the utility of RSSH donors as chemical biology tools for interrogating redox signaling and as potential pharmacological agents for the treatment of myriad pathologies associated with disrupted redox homeostasis.
Previous NMR 1 J (C13,H) –s correlations exhibited only marginal degrees of success. Presented here is a new such correlation where it is proposed NMR coupling data is passed by H–C–H and H–H pathways as suggested by the theoretical results of Provasi et al. Used where the current best values of the 1 J (C13,H)'s and molecular structure data for the hydrocarbons methane ( 1 ), ethane ( 2 ), ethene ( 3 ), benzene ( 4 ), propadiene ( 5 ), and ethyne ( 6 ). Simple equations for calculation of s character and bond angles are presented. The correlation has been extended to the case of a fluorine substituent. How the s character frameworks of molecules can be mapped out is demonstrated and compared to natural bond orbital (NBO) analysis estimations from density functional theory calculations. The definitions and calculation of the parameters in the master equation, 1 J (C13,H) = A s + n B + m C + o D + E + F , are explained in detail.
Thiosulfines as reactive S-centered 1,3-dipoles undergoing (3 + 2)-cycloadditions are still of interest in the chemistry of sulfur-rich heterocycles. The dithiirane-thiosulfine equilibrium has been revisited to elucidate possible stabilizing effects of solvents and noncovalent interactions on formation of thiosulfines. For our study, we chose compounds that have been described by various research groups. Geometries and transition states in combination with explicit and implicit solvation models have been calculated by means of DFT calculations using the r2-Scan-3c functional and compared to experimental results. Thermodynamic and kinetic properties have been investigated utilizing canonical variational transition state theory. Additionally, electronic structure properties have been considered to underline kinetic parameters. The first consideration of London dispersion and steric repulsion based on HFLD/ADLD calculations in the dithiirane-thiosulfine system in a solvation cluster is of special interest.
Research on the thermal stability of nitroform compounds remains relatively scarce, while cutting-edge reports on nitroform-based energetic materials have been increasingly emerging in recent years. In particular, thermal stability research, as a crucial indicator for the safety of nitroform compounds, deserves significant attention. Hence, the thermal stability of three chain nitroform-based bis-(1,2,4-oxadiazole) derivatives with nonlinkage, methylene and azo linkages was systematically investigated via bond order analysis, thermal decomposition calculations, electrostatic potential (ESP) mapping and frontier molecular orbital (FMO) analysis. Our results indicate that in nitroform compounds, the azo linkage may contribute to enhanced thermal stability, which is tentatively supported by its higher calculated ring-opening energy barrier (61.28 kcal mol-1), uniform ESP distribution (ESP deviation = 0.241) and enlarged HOMO-LUMO gap (9.32 eV). In contrast, the methylene linkage appears to reduce thermal stability, likely due to its poor structural symmetry and the lower ring-opening energy barrier. These findings demonstrate that azo linkages offer a dual advantage:improving thermal stability while increasing nitrogen content, providing a valuable design principle for next-generation chain nitroform-based energetic materials.
In the present research, the pyrimidine-based zwitterion (Z)-2-(2-(4,6-dimethylpyrimidin-1-ium-2-yl)hydrazono)-2-phenylacetate (L) has been synthesized through the condensation reaction of 2-hydrazino-4,6-dimethylpyrimidine and phenylglyoxylic acid. The structural characterization of L is accomplished by single crystal x-ray diffractometry (SCXRD). This organic framework is stabilized by pi-pi stacking and hydrogen-bonding intermolecular attractive forces; these weak interactions can also be seen as contributing to the stabilization of crystal self-assembly. The electronic structure of the compound was computed utilizing the density functional theory approach having M062X/def2-TZVP calculation level. Theoretically predicted structural parameters and experimentally determined structural parameters from x-ray diffraction studies are in good agreement. The stability and molecular reactivity of the compound have been assessed using FMO analysis. The molecular electrostatic potential surface map is used to determine the charge distribution throughout the molecular space. The charge transfer between the compound's donor and acceptor sites is depicted by NBO analysis. The noncovalent interaction analysis supports the existence of N-HO and N-HN interactions in compound L. Furthermore, intermolecular contacts through noncovalent interactions in the compound are investigated utilizing Hirshfeld surface analysis and fingerprint plots.
Allose, an aldohexose sugar, is a rare natural monosaccharide that occurs in nature in the form of a 6-O-cinnamyl glycoside in the leaves of the African shrub Protea rubropilosa. It differs from glucose in the orientation of the hydroxyl group at the C-3 position, being thus the C-3 substituted epimer of glucopyranose. In this paper, a detailed theoretical modeling of alpha- and beta-D-alloses was performed, including molecular dynamics (MD) simulations, high-level geometry optimizations, and GIAO-DFT NMR studies. Generally, a good correlation between calculated H-1 and C-13 NMR chemical shifts of the conformationally averaged alpha- and beta-D-alloses against experiment was found. Based on the performed calculations, the optimal combination of functionals with basis sets for the geometry optimization (M06-2X/aug-pc-2) and NMR calculations (BHandHLYP/aug-pcSseg-2) for carbohydrates was suggested.
In life, there are relationships that expand our minds and enhance our thinking in our profession. There are mentors who guide us through difficult problem-solving exercises in our profession and those who help us through those situations in life issues in general. Matthew Platz is the kind of person who has walked me through the science of photochemical reactions and also helped me to better understand the role of science and scientists in the world. Our decades long collaboration has led to multiple innovations in the use of chemistry to prevent transfusion transmitted diseases, with a global impact on blood safety and availability.
Alkyl nitrenes are highly reactive intermediates that are particularly challenging to study experimentally. Here, we report the first investigation of the simplest triplet alkyl nitrene bearing a pyridine-N-oxide moiety. Direct irradiation (lambda > 350 nm) of 4-azidomethyl-pyridine-N-oxide in an Ar matrix (15 K) generated the target triplet 4-nitrenemethyl-pyridine-N-oxide (3)2, along with E and Z isomers of 4-iminomethyl-pyridine-N-oxide 3. Results from subsequent irradiations (lambda > 325 nm) enabled the discrimination of the IR spectroscopic signatures of these species, allowing their unequivocal identification with support from DFT-B3LYP computations. Triplet nitrene (3)2 was found to be stable in dark Ar matrices, demonstrating that quantum tunneling 1,2-H shift to imine 3 is not operative on the experimental timescale. Computations show that this reaction is thermodynamically favorable on the triplet surface but involves a high-energy barrier (similar to 36 kcal mol(-1)), explaining the absence of H-tunneling. As the pyridine-N-oxide moiety can act as an anchoring site for complexation with calix[4]pyrrole derivatives, our findings open new perspectives for investigating alkyl nitrene reactivity and tunneling phenomena under supramolecular confinement conditions.
Imidazo[1,2-alpha]pyridine derivatives have garnered significant attention due to their diverse pharmacological applications, driving the development of several synthetic methodologies. Among the various strategies employed, transition metal-catalyzed condensation reactions, particularly those of the Ortoleva-King type, have emerged as a prominent approach for the synthesis of imidazo[1,2-alpha]pyridines. Despite the ongoing experimental studies, a detailed molecular mechanistic investigation of these transformations remain insufficiently elucidated. In this study, we present a comprehensive computational investigation of an Fe/I-2 assisted Ortoleva-King type reaction, employing aminopyridine and acetophenone as substrates. Using density functional theory (DFT) calculations at the unrestricted M06-L/def2-SVP level of theory, we delineate a five-step mechanistic pathway: activation of the methyl group of acetophenone by aminopyridine in the presence of molecular iodine, nucleophilic addition of 2-aminopyridine, redox reaction, water-mediated cyclization to construct the imidazo core, and final dehydration to furnish the imidazo[1,2-alpha]pyridine scaffold. Particular emphasis is placed on elucidating the role of the iron cocatalyst, the surprising participation of water in promoting cyclization in a slightly polar medium such as chlorobenzene. We find that the presence of electron-withdrawing groups on substrates has a substantial role in increasing the plausibility of the reaction.
Ketyl radicals play a key role in various reaction mechanisms, where their ability to donate hydrogen atoms governs numerous processes, ranging from photoredox catalysis to biological mechanisms and the synthesis of metal nanoparticles. Despite their significance, the thermochemical parameters that dictate their behavior remain poorly understood, leading to many inconsistencies in the literature. This minireview aims to provide a comprehensive perspective, addressing these inconsistencies that only emerge when comparing a family of reactions where available data challenge our understanding of chemical reactivity. The tables presented here, in combination with other resources, offer a robust and consistent reactivity paradigm that aligns well with the experimental reactivity of ketyl radicals.
DNA oxidation is a collection of complex processes resulting from myriad reactive intermediates. That DNA is a heterogeneous polymer and is noncovalently bound to octameric protein complexes in the nuclei of mammalian cells, presents additional challenges when carrying out mechanistic studies. Experiments on nucleosides and oligonucleotides that employ photochemical precursors to reactive intermediates have provided valuable mechanistic insight into these biologically important chemical reactions. Experiments with these molecules have facilitated resolving mechanistic questions and uncovered new chemical pathways. In this review, studies in which independently generated purine nucleobase radicals are employed are summarized.
Self-assembly of surfactants at interfaces and the structures formed are governed by complex sets of noncovalent interactions. This is exemplified in monolayers of phenolic surfactants, for example, dipalmitoylgalloylglycerol and octadecylgallate, at the air-water interface, that show unusual cohesive properties and a high degree of self-organization. The specific noncovalent interactions responsible for this behaviour are difficult to determine with experimental methods alone, which limits the rational design of phenolic thin film structures. Herein, trimers of gallate surfactant analogues have been investigated by computational methods, using omega B97X-D/6-31+G(d,p)//GFN1-xTB. Analogues varied in their tail length (methyl, ethyl or butyl), the presence of the ester moiety and the presence of hydroxy groups meta to the tail. Two arrangements were studied for each trimer: a cyclic cone arrangement, similar to that observed with phenol, and a stacked 2 + 1 pi arrangement. Each trimer was studied in the gas phase and implicit water solvent, using the GBSA model. The 2 + 1 pi arrangement is more energetically favourable than the cyclic cone arrangement when ester and/or meta hydroxy groups are introduced, despite its lack of O-H & mldr;O interactions between para hydroxy groups. In trihydroxy esters, C-H & mldr;O interactions between the ester groups and O-H & mldr;O interactions between meta hydroxy groups drive the 2 + 1 pi formation. The degree of ring-ring overlap is dictated by the presence of the ester group, highlighting the role of the headgroup-tail linker group. This study lays the groundwork for an understanding of the self-assembly and behaviour of gallate surfactant monolayers at the molecular level.
The pyrolysis of pyrrole has previously been studied in shock-tube experiments and in jet-stirred reactors. The results have been interpreted with the aid of density functional and ab initio electronic-structure calculations, in combination with kinetic models. The present work has sought to reinvestigate the mechanism and kinetics using more sophisticated electronic structure calculations and a multiwell master equation kinetic model. The intent has been not only to probe the reaction starting with pyrrole at high temperature and pressure but also to use the same mechanistic network to examine the reaction of allyl radical with center dot CN at low temperature and pressure. The question being addressed is whether the high exothermicity of this radical combination reaction could drive formation of pyrrole in extraterrestrial environments, such as the interstellar medium or in planetary atmospheres. The results reveal that two new intermediates, not considered in previous mechanisms, play important roles in the overall chemistry. Furthermore, two previously proposed mechanistic steps are found not to be viable. The master-equation analysis reveals that only traces of pyrrole would be expected to form from allyl + center dot CN, despite there being enough excess kinetic energy to overcome all barriers to its formation. An explanation for this conclusion is offered.
In this paper, two novel fluorescent probes, HBTMI-B and HBTOI-B, were designed and synthesized to detect endogenous hydrogen peroxide (H2O2) in the fermentation broth of the bioengineered bacterium Escherichia coli (E. coli DH5 alpha). By fluorescence spectroscopy experiments, the probes showed good sensitivity and selectivity in the reaction, with the fluorescence color shifting from violet to blue-green and an obvious red-shift at 300-mu M H2O2 concentration. For the theoretical calculations, the reaction mechanisms of the probe molecules during the reaction with H2O2 were investigated by using density-functional theory (DFT) and time-dependent density-functional theory (TD-DFT). In the S-1 state, the reaction barriers of the proton transfer were found to be 1.83 and 3.21 kcal/mol, respectively. Titration experiments further confirmed the high sensitivity of HBTMI-B and HBTOI-B at trace amounts of H2O2, with detection limits of 3.27 & times; 10(-7) M and 3.65 & times; 10(-7) M, respectively. In addition, biocompatibility tests showed that the two probes were non-toxic to E. coli DH5 alpha in a certain concentration range, proving their potential in biological experiments. Ultimately, the experiments validated the effectiveness of these two probes for the detection of endogenous H2O2 in bioengineered fermentation broths, which provides a new tool for the detection of hydrogen peroxide in the field of bioengineering.
