MDPI - Publisher of Open Access Journals

12 pages, 2801 KB

Open AccessArticle

Novel Vulgarin Derivatives: Chemical Transformation, In Silico and In Vitro Studies

by Hanan G. Sary, Mohammed A. Khedr and Khaled Y. Orabi

Molecules 2023, 28(8), 3421; https://doi.org/10.3390/molecules28083421 - 13 Apr 2023

Cited by 1 | Viewed by 2938

Vulgarin, an eudesmanolide sesquiterpene isolated from Artemisia judaica, was refluxed with iodine to produce two derivatives (1 and 2), which were purified and spectroscopically identified as naproxen methyl ester analogs. The reaction mechanism by which 1 and 2 were formed is explained using a sigmatropic reaction with a 1,3 shift. The scaffold hopping via lactone ring opening enabled the new derivatives of vulgarin (1 and 2) to fit well inside the COX-2 active site with ΔG of −7.73 and −7.58 kcal/mol, respectively, which was better than that of naproxen (ΔG of −7.04 kcal/mol). Moreover, molecular dynamic simulations showed that 1 was able to achieve a faster steady-state equilibrium than naproxen. The novel derivative 1 showed promising cytotoxic activities against HepG-2, HCT-116, MCF-7, and A-549 cancer cell lines compared to those of vulgarin and naproxen. Full article

(This article belongs to the Special Issue Natural Compounds: A Lead for Drug Discovery and Development)

► Show Figures

Figure 1

23 pages, 5550 KB

Open AccessArticle

4-(Aryl)-Benzo[4,5]imidazo[1,2-a]pyrimidine-3-Carbonitrile-Based Fluorophores: Povarov Reaction-Based Synthesis, Photophysical Studies, and DFT Calculations

by Victor V. Fedotov, Maria I. Valieva, Olga S. Taniya, Semen V. Aminov, Mikhail A. Kharitonov, Alexander S. Novikov, Dmitry S. Kopchuk, Pavel A. Slepukhin, Grigory V. Zyryanov, Evgeny N. Ulomsky, Vladimir L. Rusinov and Valery N. Charushin

Molecules 2022, 27(22), 8029; https://doi.org/10.3390/molecules27228029 - 19 Nov 2022

Cited by 13 | Viewed by 4724

Abstract

A series of novel 4-(aryl)-benzo[4,5]imidazo[1,2-a]pyrimidine-3-carbonitriles were obtained through the Povarov (aza-Diels–Alder) and oxidation reactions, starting from benzimidazole-2-arylimines. Based on the literature data and X-ray diffraction analysis, it was discovered that during the Povarov reaction, [1,3] sigmatropic rearrangement leading to dihydrobenzimidazo[1,2-a]pyrimidines took place. The structures of all the obtained compounds were confirmed based on the data from ¹H- and ¹³C-NMR spectroscopy, IR spectroscopy, and elemental analysis. For all the obtained compounds, their photophysical properties were studied. In all the cases, a positive emission solvatochromism with Stokes shifts from 120 to 180 nm was recorded. Aggregation-Induced Emission (AIE) has been illustrated for compound 6c using different water fractions (fw) in THF. The compounds 6c and 6f demonstrated changes in emission maxima or/and intensities after mechanical stimulation. Full article

(This article belongs to the Special Issue Synthesis of Heteroaromatic Compounds)

► Show Figures

Figure 1

27 pages, 14624 KB

Open AccessReview

The Effect of Benzannulation on the Structures, Reactivity and Molecular Dynamics of Indenes, Pentalenes, Azulenes and Related Molecules

by Michael J. McGlinchey

Molecules 2022, 27(12), 3882; https://doi.org/10.3390/molecules27123882 - 17 Jun 2022

Cited by 3 | Viewed by 3301

Abstract

The stabilising effect of benzannulation on isoindenes formed in the course of sigmatropic shifts of (C₅H₅)Fe(CO)₂ or of organo-silyl groups, and on exocyclic allyl intermediates in the course of haptotropic shifts of organometallic fragments over polycyclic skeletons (fluorene, cyclopenta[def]phenanthrene, syn and anti dibenzpentalenes) is exemplified. This approach led to the development of the first organometallic molecular brake. Benzyne cycloadditions to anthracenes to form triptycenes also led to unexpected or multiple adducts that were characterised by X-ray crystallography. Synthetic routes to the previously elusive benz[cd]azulene system are presented. Finally, the complete mechanism of the stepwise assembly of dispiro- and diindenyltetracenes from fluorenylallenes is presented, whereby every intermediate has been unambiguously structurally characterised. Full article

(This article belongs to the Special Issue Benzannulations in Organic Synthesis)

► Show Figures

Figure 1

33 pages, 20368 KB

Open AccessReview

Symmetry Breaking in NMR Spectroscopy: The Elucidation of Hidden Molecular Rearrangement Processes

by Michael J. McGlinchey

Symmetry 2014, 6(3), 622-654; https://doi.org/10.3390/sym6030622 - 4 Aug 2014

Cited by 14 | Viewed by 16683

Abstract

Variable-temperature NMR spectroscopy is probably the most convenient and sensitive technique to monitor changes in molecular structure in solution. Rearrangements that are rapid on the NMR time-scale exhibit simplified spectra, whereby non-equivalent nuclear environments yield time-averaged resonances. At lower temperatures, when the rate of exchange is sufficiently reduced, these degeneracies are split and the underlying “static” molecular symmetry, as seen by X-ray crystallography, becomes apparent. Frequently, however, such rearrangement processes are hidden, even when they become slow on the NMR time-scale, because the molecular point group remains unchanged. Judicious symmetry breaking, such as by substitution of a molecular fragment by a similar, but not identical moiety, or by the incorporation of potentially diastereotopic (chemically non-equivalent) nuclei, allows the elucidation of the kinetics and energetics of such processes. Examples are chosen that include a wide range of rotations, migrations and other rearrangements in organic, inorganic and organometallic chemistry. Full article

(This article belongs to the Special Issue Chemical Applications of Symmetry)

► Show Figures

Graphical abstract

16 pages, 754 KB

Open AccessArticle

¹⁷O-Dynamic NMR and DFT Investigation of Bis(acyloxy)iodoarenes

by Luca Fusaro, Francesca Mocci, Michel Luhmer and Giovanni Cerioni

Molecules 2012, 17(11), 12718-12733; https://doi.org/10.3390/molecules171112718 - 26 Oct 2012

Cited by 9 | Viewed by 9819

Abstract

Bis(acetoxy)iodobenzene and related acyloxy derivatives of hypervalent I(III) were studied by variable temperature solution-state ¹⁷O-NMR and DFT calculations. The ¹⁷O-NMR spectra reveal a dynamic process that interchanges the oxygen atoms of the acyloxy groups. For the first time, coalescence events could be detected for such compounds, allowing the determination of activation free energy data which are found to range between 44 and 47 kJ/mol. The analysis of the ¹⁷O linewidth measured for bis(acetoxy)iodobenzene indicates that the activation entropy is negligible. DFT calculations show that the oxygen atom exchange arises as a consequence of the [1,3]-sigmatropic shift of iodine. The calculated activation barriers are in excellent agreement with the experimental results. Both the ¹⁷O-NMR and DFT studies show that the solvent and chemical alterations, such as modification of the acyl groups or para- substitution of the benzene ring, hardly affect the energetics of the dynamic process. The low I-O Wiberg bond index (0.41–0.42) indicates a possible explanation of the invariance of both the energy barrier and the ¹⁷O chemical shift with para-substitution. Full article

(This article belongs to the Special Issue Organic Iodine Chemistry 2012)

► Show Figures

Graphical abstract

8 pages, 214 KB

Open AccessArticle

Theoretical Studies of [2,3]-Sigmatropic Rearrangements of Allylic Selenoxides and Selenimides

by Craig A. Bayse and Sonia Antony

Molecules 2009, 14(9), 3229-3236; https://doi.org/10.3390/molecules14093229 - 28 Aug 2009

Cited by 4 | Viewed by 11633

Abstract

Density-functional theory is used to model the endo and exo transition states for [2,3]-sigmatropic rearrangement of allylic aryl-selenoxides and -selenimides. The endo transition state is generally preferred for selenoxides if there is no substitution at the 2 position of the allyl group. Based upon the relative energies of the endo and exo transition states, enantioselectivity of rearrangements is expected to be greatest for molecules with substitutions at the 1- or (E)-3- position of the allyl group. Ortho substitution of a nitro group on the ancillary selenoxide phenyl ring reduces the activation barriers, increases the difference between the endo and exo activation barriers and shifts the equilibrium toward products. Full article

(This article belongs to the Special Issue Selenium and Tellurium Chemistry)

► Show Figures

Figure 1

6 pages, 33 KB

Open AccessArticle

Photomediated Transformation of Salannin, a Tetranortriterpenoid from Azadirachta indica A. Juss

by Geetha Gopalakrishnan, N. D. Pradeep Singh and V. Kasinath

Molecules 2001, 6(6), 551-556; https://doi.org/10.3390/60600551 - 31 May 2001

Cited by 6 | Viewed by 8683

Abstract

Photolysis of Salannin (1), an important bioactive compound from Azadirachta indica A.Juss (Neem), affords Δ¹⁷-isosalanninolide (2), a hitherto unknown compound, along with isosalanninolide (3) and salanninolide (4). A probable mechanism has been suggested. While the mechanism of formation of 2 involves both a [4+2] cycloaddition and a [1,3] sigmatropic shift in the furan and D-rings, respectively, formation of 3 and 4 involves the decomposition of an ozonoide-like peroxide intermediate. Full article

► Show Figures

Figure 1

Search Results (7)

Further Information

Guidelines

MDPI Initiatives

Follow MDPI

Saved Queries

Search Filter Reset All

Years

Feature Papers

Subjects

Journals

Article Types

Countries / Regions

Search Results (7)

Further Information

Guidelines

MDPI Initiatives

Follow MDPI