Substitution Of Aromatic Ring Research Articles

Exploration of thiosemicarbazone-quinolone hybrids over in-silico, antioxidant, and zebrafish embryo toxicity studies

In this study, we successfully synthesized a series of acetyl quinolone thiosemicarbazones (5a-d, 6a-d) using a simple work-up procedure yielding column-free products. The structures of the synthesized compounds were confirmed by various spectroscopic techniques, including 1H, 13C, and 2D NMR, along with FT-IR. Detailed 2D NMR analyses such as COSY, HSQC, and HMBC were also performed. The biological activities were evaluated through in-vitro, in-vivo, and in-silico studies. In-vitro antioxidant properties were assessed using radical scavenging assays, revealing significant activity for compounds 5b and 6b, likely due to the aromatic ring substitution in the thiosemicarbazide side chain. In-vivo zebrafish embryo toxicity studies indicated minimal toxicity for these compounds. Additionally, in-silico studies showed that compounds 5b and 6b have good binding energies for proteins 2C0U, 3NM8 and 2X08. Further the DFT study of HOMO and LUMO energy gap is small for 5b and 6b. These findings suggest that acetyl quinolone thiosemicarbazones are promising candidates for various biological applications due to their potent antioxidant activity and low toxicity.

Theoretical screening of N-[5'-methyl-3'-isoxasolyl]-N-[(E)-1-(-2-thiophene)] methylidene]amine and its isoxazole based derivatives as donor materials for bulk heterojunction organic solar cells: DFT and TD-DFT investigation.

In the present work, the influence of aromatic ring substitution on a series of small-donor organic molecules (A, B, C, D, and E) with isoxazole cores was investigated for photovoltaic applications in organic solar cells. Frontier molecular orbital analysis, chemical reactivity descriptors, dipole moment, and population analysis showed that all the organic materials have intramolecular charge transfer abilities capable of donating electrons to the acceptor material (PCBM). The required photovoltaic parameters such as Voc, FF, Jsc, LHE, and other associated optoelectronic parameters are reported. The results demonstrate that aromatic ring substitution influences charge transfer and power conversion efficiencies of solar cells. That is, an increase in the aromatic character of a material increases its charge transfer, and as a result, its photovoltaic properties are increased. Additionally, all the investigated derivatives are good charge transporters with suitable electron reorganization energies, which are beneficial for minimizing energy loss. Hence, these organic derivatives with isoxazole backbones are promising materials and may provide fresh insights into the design of new materials for organic solar cell applications. All calculations were performed using DFT and the ORCA 4.1.0 program package as the main tool for geometry optimization and frequency calculations. The Avogadro 1.2.1 visualization tool was used to prepare all input files executed by ORCA 4.1.0. The BP86, B3LYP, and wB97M series of functionals coupled with the def2/TZVP basis set were employed for geometry optimization. All energy-related calculations were carried out using the M06-2x functional. Multiwfn version 3.7 was used for aromaticity and population analysis. Excited state and UV-visible spectra were simulated using the TD-DFT method at the CAM-B3LYP-D3, wB97X-D3, and PBE0-D3 coupled with the ma-def2-TZVP basis set. Moreover, solvent effects were incorporated using the SMD scheme as incorporated in the ORCA software. Lastly, the RIJCOSX approximations were used to speed up calculations while maintaining accuracy.

Differentiation of regioisomeric N-substituted meta-chlorophenylpiperazine derivatives

A series ofN,N-disubstituted piperazines were synthesized containing the structural elements of meta-chlorophenylpiperazine (mCPP) in combination with methoxybenzyl-, and dimethoxybenzyl substituents to yield nineN,N-disubstituted piperazine compounds. These nine potential designer-like drug analogs were prepared based on common designer trends and regioisomeric differentiation was based on gas chromatography-mass spectrometry (GC–MS) and gas chromatography-vapor phase infrared (GC–vpIR) studies.The compounds in this study have not been reported as drugs of abuse at this time. However, commercial availability of precursor chemicals including mCPP suggests the possibility of further designer exploration. Capillary GC separation showed the regioisomers to elute according to the position of aromatic ring substitution and/or the degree of substituent crowding on the aromatic ring. Numerous electron ionization (EI) mass spectral fragment ions occur via processes initiated by one of the two nitrogen atoms of the piperazine ring. The major EI-MS fragment ions observed in all nine spectra occur at m/z 195 from the loss of the substituted benzyl radical and the cation atm/z56 (C3H6N)+from the piperazine ring. Unique radical cations at m/z 136 and m/z 152 are characteristic of the 2,3- and 3,5-dimethoxybenzyl isomers, respectively. The vapor phase infrared spectra for all nine compounds show a strong absorption band in the 1591–1593 cm−1region indicative of the chloroaniline moiety. Numerous bands in the 1600–650 cm−1region provide data for the differentiation of the methoxy and dimethoxybenzyl ring substitution patterns. Thus, a combination of EI-MS and vapor phase IR allow for the differentiation and specific identification of each regioisomer in this study.

CPD model prediction of oil sand pyrolysis based on structural parameters from 13C NMR and FTIR measurements

Here, carbon-13 nuclear magnetic resonance spectroscopy (13C NMR) and Fourier transform infrared spectroscopy (FTIR) techniques were used to study the chemical structure characteristics of oil sand and its pyrolysis oil. The FTIR results showed that the values of the CH2/CH3 ratio, A-factor, and DOC1 of the pyrolysis oil decreased during the pyrolysis process, while the C-factor showed a maximum value with increasing pyrolysis temperature. The 13C NMR results showed that methylides and methylides were mainly contributed to oil production. The aliphatic chain in the pyrolysis oil has little alterations during pyrolysis, while the extent of aromatic ring substitution increases from 0.46 to 0.58. Furthermore, a correlation was obtained between the chemical structure of oil and the pyrolysis product yields of oil sand. Moreover, using chemical structure parameters investigated with FTIR and 13C NMR and kinetic parameters based on the thermogravimetric data, the chemical percolation devolatilization (CPD) model was applied to simulate the pyrolysis of oil sand. The results showed that the simulated results for tar and light gas were in good agreement with the experimental data, while those for char underpredicted the experimental data. Overall, the CPD model can effectively predict the pyrolysis of oil sand.

Fast free energy estimates from λ-dynamics with bias-updated Gibbs sampling

Relative binding free energy calculations have become an integral computational tool for lead optimization in structure-based drug design. Classical alchemical methods, including free energy perturbation or thermodynamic integration, compute relative free energy differences by transforming one molecule into another. However, these methods have high operational costs due to the need to perform many pairwise perturbations independently. To reduce costs and accelerate molecular design workflows, we present a method called λ-dynamics with bias-updated Gibbs sampling. This method uses dynamic biases to continuously sample between multiple ligand analogues collectively within a single simulation. We show that many relative binding free energies can be determined quickly with this approach without compromising accuracy. For five benchmark systems, agreement to experiment is high, with root mean square errors near or below 1.0 kcal mol−1. Free energy results are consistent with other computational approaches and within statistical noise of both methods (0.4 kcal mol−1 or less). Notably, large efficiency gains over thermodynamic integration of 18–66-fold for small perturbations and 100–200-fold for whole aromatic ring substitutions are observed. The rapid determination of relative binding free energies will enable larger chemical spaces to be more readily explored and structure-based drug design to be accelerated.

Influence of terephthalic and orthophthalic units on the properties of polyols and polyurethane foams

The effect of aromatic ring substitution in the polyester polyol molecule on its physicochemicalproperties and on the conditions of synthesis, fire resistance and thermal stability of polyurethanefoams was investigated. The greater number of terephthalic units in the polyol results in greater viscosityand reactivity during foam formation. The obtained foams were characterized by higher thermalstability (TGA) and fire resistance (oxygen index, single flame test).

Combining infrared and Raman spectra to assess MDI localization in novel flax-reinforced automotive composites

The present work describes the use of novel flax preforms reinforcement as substitution of glass fibres in complex composite stackings made of polyurethane foam impregnated with methylene diphenyl 4, 4′-diisocyanate (MDI), for automotive headliner parts manufacturing. Headliner structure, cohesion and mechanical performances are highly dependant of MDI distribution in both foam and fibre network. This study monitors the presence and localization of MDI in the final biobased composite by implementing a robust and innovative spectroscopic methodology. For that, Infrared and Raman spectroscopies are used to characterize the fibres and polymer chemical groups, such as the isocyanate and phenyl bonds in MDI and the urethane group. MDI in the flax preform is identified by the signal of the isocyanate group in the infrared spectrum. The complementary Raman study highlight two signatures of the interaction between polyurethane and MDI. One is the shift from 1620 to 1610 cm−1 between the urethane and the MDI aromatic vibration. The second is the aromatic ring substitution at 1530 cm−1, which increases with the MDI concentration in the composite. These investigations demonstrate that MDI is present on the surfaces of flax fibres and foam and at the foam/fibre interfaces in the composite. The results clearly demonstrate the potential of flax for a use as headliner reinforcement, without penalizing the structure of the part.

Tracing the composition and structure evolution of oxygen-enriched asphaltenes during the hydrotreating of middle-low temperature coal tar

Inefficient conversion of structure-complicated and oxygen-enriched asphaltenes is found as the major challenge facing coal tar in achieving high value-added utilization. Hydrogenation technology is the primary way to achieve the impurity removal and lightweight of coal tar asphaltenes (CTAS). In this study, the evolution laws of functional groups and structural parameters at different reaction times, and pyrolysis behavior at different temperatures of coal tar asphaltenes (CTAS) during the hydrotreating (HDT) process were investigated using the methods of FT-IR, XPS, 1H NMR, 13C NMR and Py-GC/MS. It was found that the increase of the reaction time significantly affected CTAS hydrodeoxygenation (HDO), and most of nitrogen-containing compounds (NCs) and sulfur-containing compounds (SCs) could be removed in a shorter reaction time. However, the increase of the reaction time has a limited effect on the removal of NCs and SCs embedded in polycyclic aromatic compounds. The average alkyl chain length (L) decreased with the increase of the reaction time, and the degree of branching for alkyl side chains (B) increased after HDT. The aromatic ring substitution degree (σ) and alkyl substituents number (n) of CTAS increased after HDT. The OH-OH and OH-ether O were found as the major hydrogen bonds in asphaltene feed (Asp-feed) and asphaltene product (Asp-product), followed by OH-π and cyclic OH. With the increase of reaction time, the molar fraction of the OH-ether O hydrogen bonds increased, while OH-π hydrogen bonds decreased. C-O group was found as the critical oxygen-containing functional group in Asp-feed and Asp-product, primarily existing in the form of aromatic ether groups and C-O of phenols. With the increase of reaction time, the molar fraction of aromatic ether groups in CTAS increased significantly, while that of the C-O of phenols decreased. The pyrolysis fragments of Asp-feed and Asp-product were largely 1–3 ring aromatic hydrocarbons or heteroatoms compounds. Heteroatoms compounds primarily consisted of phenols and furans, whose alkyl side chains were short and few, mainly existing in the form of multiple methyl groups. The Asp-product produced smaller aromatic ring fragments, more aromatic hydrocarbons and less phenolic and non-phenolic oxygenated compounds than Asp-feed at the same pyrolysis temperatures

Various Analytical Techniques for the Isolation and Identification of Flavonoid Compounds: A Descriptive Review

Flavonoids are phytochemical compounds that can be found in a wide range of plants, including vegetables, fruits, and leaves. This vast set of phenolic plant elements can be split into numerous classes based on their diverse structures, including Flavanones, Flavanols, Flavonols, Flavones, Isoflavones, and Anthocyanins. Interestingly, they possess various applications such as natural dyes, medicinal uses, and food sources. Flavonoids have been shown to have anti-cancer, antioxidant, anti-inflammatory, and anti-viral properties in clinical studies. They also have cardio-protective and neuroprotective effects. In addition, they are responsible for the presence of different colors and flavors in various fruits, flowers, and food sources. Multiple spectroscopic techniques, including Infrared spectroscopy (IR), Ultraviolet spectroscopy (UV), and Nuclear magnetic resonance (NMR) spectroscopy, are being used to identify the structure of flavonoids. UV-Vis spectroscopy data can be used to estimate the position, type, and number of substituents present in a conjugated system. IR spectroscopy is primarily used to determine the type of functional groups and aromatic ring substitutions. The structure of Flavonoids, their type, number of protons, and carbons can be determined by NMR spectroscopy. The current review was based on searches of the Scopus, Web of Science, and Google Scholar databases for literature reviews. The purpose of this review article is to demonstrate the structure, function, and different extraction methods of flavonoids. It also summarizes the isolation and analytical identification techniques for flavonoids.

How to control the acidity of 1,2,3-triazolium ions: A density functional theory study

An exploratory study for the acidity of 1,2,3-triazolium ions has been carried out by using the density functional theory (DFT). The prototype of 1,2,3-triazolium ion 2a is calculated to have a pKa of 24.0 ± 0.1. Substitution at N (1) or C (4) on the heterocycle by a tolyl group increases the acidity by about 0.3 pKa unit (pKa (3a) = 23.7 ± 0.1). Electron-withdrawing groups on the aromatic ring increases the acidity by approximately three pKa units (pKa (4b) = 20.9 ± 0.4). The 1,2,3-triazolium ions are less acidic than the corresponding 1,2,4-triazolium and imidazolium ions. The weaker acidity may be explained by the position of the carbene precursor C–H group, which is located between one nitrogen and one carbon atom in the heterocycle. This exploratory study shows that the acidity of the 1,2,3-triazolium ions can be modified by aromatic ring substitutions at N (1) or C (4) positions on the heterocycle, and further by the substituents on the aromatic rings.

Functionalized Tris(anilido)triazacyclononanes as Hexadentate Ligands for the Encapsulation of U(III), U(IV) and La(III) Cations

Tripodal multidentate ligands have become increasingly popular in f-element chemistry for stabilizing unusual bonding motifs and supporting small molecule activation processes. The steric and electronic effects of ligand donor atom substituents have proved crucial in both of these applications. In this study we functionalized the previously reported tris-anilide ligand {tacn(SiMe2NPh)3} (tacn = 1,3,7-triazacyclononane) to incorporate substituted aromatic rings, with the aim of modifying f-element complex solubility and ligand steric effects. We report the synthesis of two proligands, {tacn(SiMe2NHAr)3} (Ar = C6H3Me2-3,5 or C6H4Me-4), and their respective group 1 transfer agents—{tacn(SiMe2NKAr)3}, M(III) complexes [M{tacn(SiMe2NAr)3}] for M = La and U, and U(IV) complexes [M{tacn(SiMe2NAr)3}(Cl)]. These compounds were characterized by multinuclear NMR and FTIR spectroscopy and elemental analysis. The paramagnetic uranium complexes were also characterized by solid state magnetic measurements and UV/Vis/NIR spectroscopy. U(III) complexes were additionally studied by EPR spectroscopy. The solid state structures of all f-block complexes were authenticated by single-crystal X-ray diffraction (XRD), together with a minor byproduct [U{tacn(SiMe2NC6H4Me-4)3}(I)]. Comparisons of the characterization data of our f-element complexes with similar literature examples containing the {tacn(SiMe2NPh)3} ligand set showed minor changes in physicochemical properties resulting from the different aromatic ring substitution patterns we investigated.

Low temperature oxidized coke of the ultra-heavy oil during in-situ combustion process: Structural characterization and evolution elucidation

Fundamental knowledge on the evolution of low temperature oxidized coke was a prerequisite towards a deep understanding of coke deposition and subsequent combustion of ultra-heavy oils during in-situ combustion (ISC) process. This study investigated the structural characterization (oxidation behavior, elemental composition, functional groups, and morphology) and elucidated evolution mechanism of cokes generated from the low temperature oxidation/pyrolysis of the ultra-heavy oil during ISC process. The results shown that, compared with pyrolytic coke, the intermediate groups of C-O/C-OH (1260–1060 cm−1) were further oxidized into C = O (1850–1650 cm−1) groups and finally converted into C = C groups (“coke peak”, 1590 cm−1) in highly conjugated aromatic structures for oxidized cokes. Besides, the oxidized coking condition would result in a higher degree of substitution (γCHAr1, γCHAr4) of aromatic rings (900–700 cm−1) and promote the evolution of N- and S- functional groups. Although >78 % of C 1 s belonged to the graphitic carbon for four cokes, morphologies of oxidized cokes were relatively coarse with much looser distribution. In addition, the corresponding enthalpies were in the order cokeLTO3 (25.51 kJ·g−1) > cokeLTP (24.22 kJ·g−1) > cokeLTO2 (23.23 kJ·g−1) > cokeLTO1 (17.45 kJ·g−1), indicating a considerable contribution of low temperature oxidation reactions on derived coke morphology, oxidizability and exothermicity, which contained complicated and crucial dehydrogenation, crosslinking and polymerization reactions to accelerate coke evolution.

Development of Novel Isoindolone-Based Compounds against Trypanosoma brucei rhodesiense.

This study identified the isoindolone ring as a scaffold for novel agents against Trypanosoma brucei rhodesiense and explored the structure‐activity relationships of various aromatic ring substitutions. The compounds were evaluated in an integrated in vitro screen. Eight compounds exhibited selective activity against T. b. rhodesiense (IC50<2.2 μm) with no detectable side activity against T. cruzi and Leishmania infantum. Compound 20 showed low nanomolar potency against T. b. rhodesiense (IC50=40 nm) and no toxicity against MRC‐5 and PMM cell lines and may be regarded as a new lead template for agents against T. b. rhodesiense. The isoindolone‐based compounds have the potential to progress into lead optimization in view of their highly selective in vitro potency, absence of cytotoxicity and acceptable metabolic stability. However, the solubility of the compounds represents a limiting factor that should be addressed to improve the physicochemical properties that are required to proceed further in the development of in vivo‐active derivatives.

GC–MS and GC–IR of regioisomeric 4-N-methoxy- and dimethoxybenzyl derivatives of 3-trifluoromethylphenylpiperazine

A series of nine N,N-disubstituted piperazines were synthesized containing the structural elements of 3-trifluoromethylphenylpiperazine (3-TFMPP) in combination with each of the three regioisomeric monomethoxybenzyl-, and six regioisomeric dimethoxybenzyl substituents to yield the nine N,N-disubstituted piperazine compounds. These nine potential designer drug analogues were prepared based on common designer modifications of the known novel psychoactive substance 3-TFMPP and compared in GC–MS and GC–IR studies. The GC separation on an Rxi®-17Sil MS stationary phase showed the regioisomers of the methoxybenzyl to elute according to the position of aromatic ring substitution with the 2- isomer eluting before the 3-isomer and the 4- methoxybenzyl isomer eluting last. The six regioisomeric dimethoxybenzyl analogues eluted according to the degree of substituent crowding with the 2,3- and 2,6-isomers eluting first and the 3,5-isomer last. Numerous EI mass spectral fragment ions occur via processes initiated by one of the two nitrogen atoms of the piperazine ring. The major EI-MS fragment ions are at m/z 229 observed in all nine spectra occurs from the loss of the substituted benzyl radical and the m/z 56 cation (C3H6N)+ originates from the piperazine ring. Other characteristic fragments containing the benzyl portion of these analogues show a 30 Da variation based on the number of methoxy group substituents. The relative intensity of ions in the methoxybenzyl series as well as some unique ions in the dimethoxybenzyl series provides initial points of preliminary differentiation. These results coupled with characteristic vapor phase infrared spectra allow for the identification of each regioisomer.

Extraction of Fulvic Acid from Lignite and Characterization of Its Functional Groups.

Fulvic acid (FA) is a complex organic mixture composed of small molecules. The structure and composition of FA vary greatly because of the different raw materials used for preparing FA. In this work, FA was extracted from shallow low-rank lignite by hydrogen peroxide (H2O2) in a microwave field, and the functional groups of FA were characterized. The optimal extraction process was determined, with the H2O2 concentration being the key factor affecting the yield of FA. Thermogravimetric analysis showed that FA was mainly composed of low molecular weight and readily pyrolyzed compounds. As shown by Fourier transform infrared spectroscopy, in the process of FA extraction by H2O2 oxidation of lignite, the content of −COOH increased, long-chain aliphatic compounds decreased, stretching vibrations of aromatic ring skeletons disappeared, and aromatic ring substitution became mainly tri- or disubstitution. Fluorescence spectroscopy indicated that FA had a low degree of aromaticity. X-ray photoelectron spectroscopy qualitatively and quantitatively revealed that the main modes of carbon–oxygen bonding in FA were C–O–, COO–, and C=O. Thus, this study not only lays a foundation for studying the composition and structure of coal-based FA but also opens a new avenue for a clean and efficient utilization of lignite.

GC–MS analysis of N-(bromodimethoxybenzyl)-2-, 3-, and 4-methoxyphenethylamines: Inverse analogues of the psychoactive 25B-NBOMe drug

The substituted phenethylamine analogues in this study are derivatives of N-(2-methoxybenzyl)-4-bromo-2,5-dimethoxyphenethylamine (25B-NBOMe) having the reverse substitution pattern for the two aromatic rings. These compounds contain only a single methoxy substituent in the phenethylamine part, and a bromodimethoxy substitution pattern in the benzyl portion. The regioisomers were prepared with variations in the substitution pattern in both the bromodimethoxy substitution pattern of the benzyl part as well as the methoxy substitution pattern in the phenethylamine part. The nine regioisomeric compounds were prepared from the regioisomeric 2-, 3-, and 4- methoxyphenethylamines via N-reductive alkylation with the three regioisomeric 2,4,5-substituted bromodimethoxybenzaldehydes.The EI-MS spectra of these regioisomers gave two major bromine containing ions at m/z 229/231 (base peak) and 258/260 and two non-brominated fragments at m/z 91 and 121. The relative abundance of the m/z 91 was higher for the 2-methoxyphenethylamine substituted isomers and the relative abundance of the m/z 121 fragment was higher in the 4-methoxy substituted isomers. The gas chromatographic separation for the regioisomeric methoxyphenethylamines of each bromodimethoxybenzyl aromatic ring substitution pattern showed the 2-methoxyphenethylamine substituted isomer eluted first followed by the 3-substituted isomer and the 4-methoxyphenethylamine substituted isomer was the last to elute and the three bromodimethoxybenzyl regioisomers for the 2-methoxyphenethylamine subseries were resolved as the trifluoroacetamides. The EI-MS for the TFA derivatives of the 2-bromo-4,5-dimethoxybenzyl substituted isomer gave unique fragment ions resulting from displacement of bromine from the molecular ion. This fragmentation pathway was confirmed using the model compounds N-(2-, 3- and 4-bromobenzyl)phenethylamine trifluoroacetamides.

Index of ideality of correlation and correlation contradiction index: a confluent perusal on acetylcholinesterase inhibitors

ABSTRACT Alzheimer’s disease is one of the leading causes of disability and death in the global scenario. Acetylcholinesterase inhibitors are symptomatically involved in the therapeutic management of Alzheimer’s disease. Due to the prophetic capability of SMILES-based QSAR studies, the current method explored its efficiency for designing novel inhibitors of acetylcholinesterase enzyme. Two newly introduced validation parameters (the ideality of correlation (IIC) and the correlation contradiction index (CCI)) were studied for further validating the predictive capability of developed models. The index of ideality of correlation was found to have a positive effect on models developed in comparison to models developed without IIC. The structural features accountable for intensifying the inhibitory activity were identified by performing QSAR modelling studies on 60 acetylcholinesterase inhibitors from the literature. Based on the molecular features identified designing of new molecules was accomplished and was found to have satisfactory inhibitory potential. Docking interactions of designed molecules pointed the importance of position of nitro group, aromatic ring and alkyl substitution in influencing the inhibitory activity and binding interactions. The designed compound DD2 was found to have highest inhibitory potential (4.33) and binding affinity (−11.2 kcal mol−1).

Ab initio and NBO studies of methyl internal rotation in 1-methyl-2(1H)-quinolinone: effect of aromatic substitution to 1-methyl-2(1H)-pyridone.

1-methyl-2(1H)-quinolinone (MeQone) forms the framework of several hundred alkaloid molecules both natural and synthetic being used for various biological applications. From chemical structure point of view, the molecules can also be seen as an aromatic ring fused to 1-methyl-2(1H)-pyridone (1-MPY). In this work, we present theoretical investigations on internal rotation of methyl group in MeQone in light of 1-MPY. We looked into the change in the three-fold (V3) methyl internal rotation barrier resulted from the aromatic ring substitution to 1-MPY. The V3 term in two molecules were calculated using density functional theory and Hartree-Fock theory with different basis sets. MeQone has calculated V3 term (in S0 state) three times higher in magnitude compared with that of 1-MPY. The role of aromatic substitution in increase of V3 term is investigated using natural bond orbital (NBO) analyses. In the NBO analysis, it is found that the aromatic ring as highly delocalized π-system lowers the magnitude of hyperconjugation energy in MeQone compared with 1-MPY. This is due to the extension of delocalization of π-electrons to pyridone ring which lowers the orbital overlap. However, the Lewis energy increases substantially and make the overall barrier energy higher in MeQone compared with 1-MPY. From our study, we conclude that in the molecules such as 1-MPY and MeQone where the methyl group has two single bonds vicinal to it, the overall hyperconjugation energy is always barrier forming with nonlocal interactions playing significant role. Also, the Lewis energy plays the decisive role in barrier formation, and its magnitude can be tuned by tuning the π-electron delocalization. We have also looked into the change in methyl group conformation upon electronic excitation to S1 state. In 1-MPY, the methyl group rotated by 60° upon excitation whereas in MeQone, there was no conformational change. Strong π*-σ* interaction in LUMO in top-of-barrier conformation is responsible for the change in the methyl group conformation in 1-MPY, whereas same π*-σ* interaction in LUMO of minimum energy conformation results in unchanged excited state conformation in MeQone. Graphical abstract.

Structure fragmentation studies of ring-substituted N-trifluoroacetyl-N-benzylphenethylamines related to the NBOMe drugs.

The halogenated derivatives of N-(2-methoxy)benzyl-2,5-dimethoxyphenethylamine (25-NBOMe) such as the 4-bromo analogue (25B-NBOMe) represent a new class of hallucinogenic or psychedelic drugs. The purpose of this study was to determine the role of the electron-donating groups (halogen and dimethoxy) in the pathway of decomposition for the distonic molecular radical cation in the electron ionization mass spectrometry (EI-MS) process of the trifluoroacetamide (TFA) derivatives. The systematic removal of substituents from the 4-halogenated 2,5-dimethoxyphenethylamine portion of the N-dimethoxybenzyl NBOMe analogues allowed an evaluation of structural effects on the formation of major fragment ions in the EI-MS of the TFA derivatives. All six regioisomeric dimethoxybenzyl-substituted analogues (2,3-, 2,4-, 2,5-, 2,6-, 3,4- and 3,5-dimethoxy) for the four series of phenethyl aromatic ring substitution patterns were prepared, derivatized and analyzed via gas chromatography coupled with EI-MS. The analogues yield two unique radical cation fragments from the decomposition of the common distonic molecular radical cation. The substituted phenylethene radical cation (m/z 164) is the base peak or second most abundant ion in all six TFA-2,5-dimethoxyphenethylamine isomers. The dimethoxybenzyltrifloroacetamide radical cation (m/z 263) is the base peak or second most abundant ion in the 2- and 3-monomethoxyphenethylamine isomers. However, the 2- and 3-methoxyphenylethene radical cation (m/z 134) is among the five most abundant ions for each of these twelve isomers. Only one isomer in the phenethylamine series yields the corresponding unsubstituted phenylethene radical cation at m/z 104. The decomposition of the hydrogen-rearranged distonic molecular radical cation favors formation of the dimethoxybenzyltrifloroacetamide (m/z 263) species for the less electron-rich phenethyl aromatic rings. The addition of electron-donating groups to the aromatic ring of the phenethyl group as in the NBOMe-type molecules shifts the decomposition of the common distonic molecular radical cation to favor the formation of the electron-rich substituted phenylethene radical cation.

Tailoring Ultrafast Singlet Fission by the Chemical Modification of Phenazinothiadiazoles.

Quantum chemistry and time-resolved spectroscopy are applied to rationalize how singlet fission (SF) is affected by systematic chemical modifications introduced into phenazinothiadiazoles (PTD). Substitution of the terminal aromatic ring of TIPS-tetracene by a thiadiazole group leads to a considerable change in the relative energies of its S1 and T1 states. Thus, in contrast to TIPS-tetracene, SF becomes exothermic for various PTD derivatives, which show S1-2T1 energy differences as high as 0.15 eV. This enables SF in PTD as corroborated by femtosecond transient absorption spectroscopy and TD-DFT calculations. The latter report T-T spectra consistent with thin film UV-vis femtosecond transient absorption of PTDs at long delays. TD-DFT calculations also show that the S1-T1 energy gap can be rationally tuned by introducing N atoms into the aromatic scaffold and by the halogenation of one side ring of the PTD. In addition, the specific S1-to-1(T1T1) electronic coupling depends on the crystal morphology and the electronic properties simultaneously. Thus, both of them govern the strength and the interplay between direct and superexchange couplings, which in the most favorable cases accelerate SF to rate constants beyond (100 fs)-1. Remarkably, direct coupling was found to contribute considerably to the total effective coupling and even to dominate it for some PTDs investigated here. A quantum yield of 200% is obtained on the early picosecond time scale for all compounds studied here, which is reduced to 100% due to triplet-triplet annihilation after a few nanoseconds.