International Journal of Molecular Sciences

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5 pages, 176 KiB

Open AccessEditorial

Highlights from the Special Issue Titled “Recent Advances in Organic Chemistry: Molecules Synthesis and Reactions”

by Rachid Chahboun and José Justicia

Int. J. Mol. Sci. 2025, 26(6), 2787; https://doi.org/10.3390/ijms26062787 - 19 Mar 2025

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Abstract

Organic synthesis, the art and science of constructing complex organic compounds from simpler ones, is one of the most important fields of research in organic chemistry [...] Full article

(This article belongs to the Special Issue Recent Advances in Organic Chemistry: Molecules Synthesis and Reactions)

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14 pages, 1733 KiB

Open AccessArticle

Facile Synthesis of Pyridyl Rosamines as Potential Photosensitizers

by Éva Bakos, Henrietta Ágoston, Rebeka Ignácz, Attila Hunyadi, Miklós Poór, János Erostyák, Zoltán Kele, Csilla Özvegy-Laczka and Erzsébet Mernyák

Int. J. Mol. Sci. 2025, 26(4), 1482; https://doi.org/10.3390/ijms26041482 - 10 Feb 2025

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Abstract

Rosamines represent one of the most promising groups of xanthene dyes. Their excellent photophysical properties allow their widespread application. Their use as photosensitizers in photodynamic therapy has recently gained considerable attention. Here, we report the facile, effective, microwave-assisted synthesis of rosamine dyes. Pyridylbenzaldehyde [...] Read more.

Rosamines represent one of the most promising groups of xanthene dyes. Their excellent photophysical properties allow their widespread application. Their use as photosensitizers in photodynamic therapy has recently gained considerable attention. Here, we report the facile, effective, microwave-assisted synthesis of rosamine dyes. Pyridylbenzaldehyde derivatives were reacted with 1,3-dialkylaminophenols or 8-hydroxyjulolidine in toluene without any additive. The resulting pyridyl rosamines were investigated for their cytotoxic effect against the A431 human epidermoid carcinoma cell line to estimate their potential as photosensitizers. The compounds displayed light-induced toxicity in the submicromolar or occasionally in the low nanomolar range. One of the julolidine-based derivatives exhibited a phototoxic index above 100, indicating an increase in light-induced cytotoxic efficacy of two orders of magnitude compared to its negligible dark toxicity. This compound is a particularly promising candidate for the development of novel pyridyl-rosamine-based photosensitizers for photodynamic therapy of skin cancer. Full article

(This article belongs to the Special Issue Recent Advances in Organic Chemistry: Molecules Synthesis and Reactions)

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19 pages, 8747 KiB

Open AccessArticle

Stereoview Images of Hydrogen-Bonded Quinoxalines with a Helical Axis; Pyrimidines and a Pyridazine That Form Extended Tapes

by Michael John Plater and William T. A. Harrison

Int. J. Mol. Sci. 2024, 25(22), 12329; https://doi.org/10.3390/ijms252212329 - 17 Nov 2024

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Abstract

Different supramolecular motifs are formed by the crystallisation of amino-substituted derivatives of quinoxaline, pyrimidine and pyridazine. These were made from the corresponding mono- or dichlorinated heterocycles by a nucleophilic displacement reaction. The pyridine-type nitrogen atoms activate the chlorine atoms because they can stabilise [...] Read more.

Different supramolecular motifs are formed by the crystallisation of amino-substituted derivatives of quinoxaline, pyrimidine and pyridazine. These were made from the corresponding mono- or dichlorinated heterocycles by a nucleophilic displacement reaction. The pyridine-type nitrogen atoms activate the chlorine atoms because they can stabilise a negative charge, which forms when the amine attacks the ring. One amino group can be attached under mild conditions in hot ethanol or acetonitrile, but the first then deactivates the ring so the second requires more forceful conditions using a pressure vessel at 150 °C. Butylamine is frequently used because it reduces the polarity of the product, making it easier to purify and isolate. The extended structure of the quinoxaline derivatives 16–18 show a common ‘pincer’ hydrogen-bond motif, with a quinoxaline nitrogen atom accepting two N–H···N hydrogen bonds, giving a spiral or helical axis. The chain symmetries are 4₁, 2₁ and 3₁, respectively, depending on the substituents. A stereoview of each is shown. The pyrimidine derivatives 19, 12, 20, 14 and 21 form hydrogen-bonded tapes and compound 20 forms inversion dimers. Full article

(This article belongs to the Special Issue Recent Advances in Organic Chemistry: Molecules Synthesis and Reactions)

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13 pages, 4395 KiB

Open AccessArticle

NBS-Mediated C(sp²)-H Bond Chlorination of Enaminones: Using DCE as Chlorine Source

by Menglin Peng, Yunhua Xie, Siyu Song, Zhilai Zhang, Yuanzheng Wei, Huimin Hu, Yongchao Wang and Fuchao Yu

Int. J. Mol. Sci. 2024, 25(22), 12073; https://doi.org/10.3390/ijms252212073 - 10 Nov 2024

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Abstract

Commercial DCE is excavated as both a “Cl” source and a solvent for the vinyl C(sp²)-H chlorination. The strategy involves a metal-free NBS-mediated C(sp²)-H chlorination of enaminones, and affords diverse, functionalized α-chlorinated enaminones with a Z-configuration. This [...] Read more.

Commercial DCE is excavated as both a “Cl” source and a solvent for the vinyl C(sp²)-H chlorination. The strategy involves a metal-free NBS-mediated C(sp²)-H chlorination of enaminones, and affords diverse, functionalized α-chlorinated enaminones with a Z-configuration. This mild and effective approach not only advances the vinyl C(sp²)-H chlorination, employing DCE as the “Cl” source, but also provides a new strategy for accessing chlorinated enaminone derivatives. Full article

(This article belongs to the Special Issue Recent Advances in Organic Chemistry: Molecules Synthesis and Reactions)

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13 pages, 2686 KiB

Open AccessArticle

Synthesis and Biological Evaluation of Novel Furopyridone Derivatives as Potent Cytotoxic Agents against Esophageal Cancer

by Xingyu Ren, Jiaojiao Zhang, Anying Dai, Pengzhi Sun, Yibo Zhang, Lu Jin and Le Pan

Int. J. Mol. Sci. 2024, 25(17), 9634; https://doi.org/10.3390/ijms25179634 - 5 Sep 2024

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Abstract

Cancer continues to be a major global health issue, ranking among the top causes of death worldwide. To develop novel antitumor agents, this study focused on the synthesis of a series of 21 novel furanopyridinone derivatives through structural modifications and functional enhancements. The [...] Read more.

Cancer continues to be a major global health issue, ranking among the top causes of death worldwide. To develop novel antitumor agents, this study focused on the synthesis of a series of 21 novel furanopyridinone derivatives through structural modifications and functional enhancements. The in vitro anti-tumor activities of these compounds were investigated through the cytotoxicity against KYSE70 and KYSE150 and led to the identification of compound 4c as the most potent compound. At a concentration of 20 µg/mL, compound 4c demonstrated a remarkable 99% inhibition of KYSE70 and KYSE150 cell growth after 48 h. IC₅₀ was 0.655 µg/mL after 24 h. Additionally, potential anti-tumor cellular mechanisms were explored through molecular docking, which was used to predict the binding mode of 4c with METAP2 and EGFR, suggesting that the C=O part of the pyridone moiety likely played a crucial role in binding. This study provided valuable insights and guidance for the development of novel anticancer drugs with novel structural scaffolds. Full article

(This article belongs to the Special Issue Recent Advances in Organic Chemistry: Molecules Synthesis and Reactions)

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14 pages, 3444 KiB

Open AccessArticle

Sequential Nucleophilic Aromatic Substitution Reactions of Activated Halogens

by M. John Plater and William T. A. Harrison

Int. J. Mol. Sci. 2024, 25(15), 8162; https://doi.org/10.3390/ijms25158162 - 26 Jul 2024

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Abstract

Building blocks have been identified that can be functionalised by sequential nucleophilic aromatic substitution. Some examples are reported that involve the formation of cyclic benzodioxin and phenoxathiine derivatives from 4,5-difluoro-1,2-dinitrobenzene, racemic quinoxaline thioethers, and sulfones from 2,3-dichloroquinoxaline and (2-aminophenylethane)-2,5-dithiophenyl-4-nitrobenzene from 1-(2-aminophenylethane)-2-fluoro-4,5-dinitrobenzene. Four X-ray [...] Read more.

Building blocks have been identified that can be functionalised by sequential nucleophilic aromatic substitution. Some examples are reported that involve the formation of cyclic benzodioxin and phenoxathiine derivatives from 4,5-difluoro-1,2-dinitrobenzene, racemic quinoxaline thioethers, and sulfones from 2,3-dichloroquinoxaline and (2-aminophenylethane)-2,5-dithiophenyl-4-nitrobenzene from 1-(2-aminophenylethane)-2-fluoro-4,5-dinitrobenzene. Four X-ray single-crystal structure determinations are reported, two of which show short intermolecular N–O^…N “π hole” contacts. Full article

(This article belongs to the Special Issue Recent Advances in Organic Chemistry: Molecules Synthesis and Reactions)

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9 pages, 1962 KiB

Open AccessCommunication

Synthesis of 3,4-Disubstituted Maleimide Derivatives via Phosphine-Catalyzed Isomerization of α-Succinimide-Substituted Allenoates Cascade γ′-Addition with Aryl Imines

by Zhenzhen Gao, Xiaoming Zhou, Baoshen Nie, Hanchong Lu, Xiaotong Chen, Jiahui Wu, Xuekun Wang and Lei Li

Int. J. Mol. Sci. 2024, 25(13), 6916; https://doi.org/10.3390/ijms25136916 - 24 Jun 2024

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Abstract

3,4-disubstituted maleimides find wide applications in various pharmacologically active compounds. This study presents a highly effective approach for synthesizing derivatives of 3,4-disubstituted maleimides through the direct isomerization of α-succinimide-substituted allenoates, followed by a cascade γ′-addition and aryl imines using PR₃ as a [...] Read more.

3,4-disubstituted maleimides find wide applications in various pharmacologically active compounds. This study presents a highly effective approach for synthesizing derivatives of 3,4-disubstituted maleimides through the direct isomerization of α-succinimide-substituted allenoates, followed by a cascade γ′-addition and aryl imines using PR₃ as a catalyst. The resulting series of 3,4-disubstituted maleimides exhibited excellent stereoselectivities, achieving yields of up to 86%. To our knowledge, the phosphine-mediated γ′-addition reaction of allenoates is seldom reported. Full article

(This article belongs to the Special Issue Recent Advances in Organic Chemistry: Molecules Synthesis and Reactions)

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12 pages, 2185 KiB

Open AccessArticle

Synthesis and Study of Building Blocks with Dibenzo[b,f]oxepine: Potential Microtubule Inhibitors

by Piotr Tobiasz, Filip Borys, Marta Kucharska, Marcin Poterała and Hanna Krawczyk

Int. J. Mol. Sci. 2024, 25(11), 6155; https://doi.org/10.3390/ijms25116155 - 3 Jun 2024

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Abstract

The synthesis of biphenylmethoxydibenzo[b,f]oxepine or photoswitchable fluorinated dibenzo[b,f]oxepine derivatives with one or three azo bonds, potential microtubule inhibitors, is described. Our studies provide a concise method for constructing derivatives containing the dibenzo[b,f]oxepine skeleton. An analysis of products [...] Read more.

The synthesis of biphenylmethoxydibenzo[b,f]oxepine or photoswitchable fluorinated dibenzo[b,f]oxepine derivatives with one or three azo bonds, potential microtubule inhibitors, is described. Our studies provide a concise method for constructing derivatives containing the dibenzo[b,f]oxepine skeleton. An analysis of products was run using experimental and theoretical methods. Next, we evaluated the E/Z isomerization of azo-dibenzo[b,f]oxepine derivatives, which could be photochemically controlled using visible-wavelength light. Full article

(This article belongs to the Special Issue Recent Advances in Organic Chemistry: Molecules Synthesis and Reactions)

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14 pages, 4002 KiB

Open AccessArticle

Sustainable and Safe N-alkylation of N-heterocycles by Propylene Carbonate under Neat Reaction Conditions

by Andrea Czompa, Dóra Bogdán, Balázs Balogh, Eszter Erdei, Patrik Selymes, Attila Csomos and István M. Mándity

Int. J. Mol. Sci. 2024, 25(10), 5523; https://doi.org/10.3390/ijms25105523 - 18 May 2024

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Abstract

A new, eco-friendly process utilising the green solvent propylene carbonate (PC) has been developed to perform N-alkylation of N-, O- and/or S-containing heterocyclic compounds. PC in these reactions served as both the reagent and solvent. Importantly, no genotoxic alkyl [...] Read more.

A new, eco-friendly process utilising the green solvent propylene carbonate (PC) has been developed to perform N-alkylation of N-, O- and/or S-containing heterocyclic compounds. PC in these reactions served as both the reagent and solvent. Importantly, no genotoxic alkyl halides were required. No auxiliary was necessary when using anhydrous PC. Product formation includes nucleophilic substitution with the concomitant loss of water and carbon dioxide. Substrates prepared, including the newly invented PROTAC drugs, are widely used. Full article

(This article belongs to the Special Issue Recent Advances in Organic Chemistry: Molecules Synthesis and Reactions)

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9 pages, 1506 KiB

Open AccessCommunication

Chiral Thianthrenes

by M. John Plater and William T. A. Harrison

Int. J. Mol. Sci. 2024, 25(8), 4311; https://doi.org/10.3390/ijms25084311 - 13 Apr 2024

Cited by 2 | Viewed by 1180

Abstract

The absolute configuration and stability of two thianthrene chiral sulfoxides has been determined by means of X-ray single-crystal structure determinations. The analyses and configurations allow verification that the diastereomeric sulfoxides are stable in solution and are not interconverting, which has been suggested in [...] Read more.

The absolute configuration and stability of two thianthrene chiral sulfoxides has been determined by means of X-ray single-crystal structure determinations. The analyses and configurations allow verification that the diastereomeric sulfoxides are stable in solution and are not interconverting, which has been suggested in some studies of sulfoxides. The two thianthrene sulfoxides have slightly different R_f values, which allowed their separation using flash chromatography on silica. The spots run back-to-back, which posed a challenge for their separation. The pure, separated compounds in solution remain as separate, single spots on a Thin Layer Chromatography (TLC) plate. Full article

(This article belongs to the Special Issue Recent Advances in Organic Chemistry: Molecules Synthesis and Reactions)

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Review

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39 pages, 10969 KiB

Open AccessReview

Click Chemistry as an Efficient Toolbox for Coupling Sterically Hindered Molecular Systems to Obtain Advanced Materials for Nanomedicine

by Neyra Citlali Cabrera-Quiñones, Luis José López-Méndez, Carlos Cruz-Hernández and Patricia Guadarrama

Int. J. Mol. Sci. 2025, 26(1), 36; https://doi.org/10.3390/ijms26010036 - 24 Dec 2024

Cited by 1 | Viewed by 1566

Abstract

Since its conceptualization, click chemistry in all its variants has proven to be a superior synthesis protocol, compared to conventional methods, for forming new covalent bonds under mild conditions, orthogonally, and with high yields. If a term like reactive resilience could be established, [...] Read more.

Since its conceptualization, click chemistry in all its variants has proven to be a superior synthesis protocol, compared to conventional methods, for forming new covalent bonds under mild conditions, orthogonally, and with high yields. If a term like reactive resilience could be established, click reactions would be good examples, as they perform better under increasingly challenging conditions. Particularly, highly hindered couplings that perform poorly with conventional chemistry protocols—such as those used to conjugate biomacromolecules (e.g., proteins and aptamers) or multiple drugs onto macromolecular platforms—can be more easily achieved using click chemistry principles, while also promoting high stereoselectivity in the products. In this review, three molecular platforms relevant in the field of nanomedicine are considered: polymers/copolymers, cyclodextrins, and fullerenes, whose functionalization poses a challenge due to steric hindrance, either from the intrinsic bulk behavior (as in polymers) or from the proximity of confined reactive sites, as seen in cyclodextrins and fullerenes. Their functionalization with biologically active groups (drugs or biomolecules), primarily through copper-catalyzed azide–alkyne cycloaddition (CuAAC), strain-promoted azide–alkyne cycloaddition (SPAAC), inverse electron-demand Diels–Alder (IEDDA) and thiol–ene click reactions, has led to the development of increasingly sophisticated systems with enhanced specificity, multifunctionality, bioavailability, delayed clearance, multi-targeting, selective cytotoxicity, and tracking capabilities—all essential in the field of nanomedicine. Full article

(This article belongs to the Special Issue Recent Advances in Organic Chemistry: Molecules Synthesis and Reactions)

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