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16 pages, 4125 KiB

Open AccessArticle

Hybrid Zn-β-Aminoporphyrin–Carbon Nanotubes: Pyrrolidine and Direct Covalent Linkage Recognition, and Multiple-Photo Response

by Susana L. H. Rebelo, César A. T. Laia, Monika Szefczyk, Alexandra Guedes, Ana M. G. Silva and Cristina Freire

Molecules 2023, 28(21), 7438; https://doi.org/10.3390/molecules28217438 - 5 Nov 2023

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Abstract

To unveil and shape the molecular connectivity in (metallo)porphyrin–carbon nanotube hybrids are of main relevance for the multiple medicinal, photoelectronic, catalytic, and photocatalytic applications of these materials. Multi-walled carbon nanotubes (MWCNTs) were modified through 1,3-dipolar cycloaddition reactions with azomethine ylides generated in situ [...] Read more.

To unveil and shape the molecular connectivity in (metallo)porphyrin–carbon nanotube hybrids are of main relevance for the multiple medicinal, photoelectronic, catalytic, and photocatalytic applications of these materials. Multi-walled carbon nanotubes (MWCNTs) were modified through 1,3-dipolar cycloaddition reactions with azomethine ylides generated in situ and carrying pentafluorophenyl groups, followed by immobilization of the β-amino-tetraphenylporphyrinate Zn(II). The functionalities were confirmed via XPS and FTIR, whereas Raman spectroscopy showed disruptions on the graphitic carbon nanotube surface upon both steps. The functionalization extension, measured via TGA mass loss and corroborated via XPS, was 0.2 mmol·g⁻¹. Photophysical studies attest to the presence of the different porphyrin–carbon nanotube connectivity in the nanohybrid. Significantly different emission spectra and fluorescence anisotropy of 0.15–0.3 were observed upon variation of excitation wavelength. Vis-NIR absorption and flash photolysis experiments showed energy/charge transfer in the photoactivated nanohybrid. Moreover, evidence was found for direct reaction of amino groups with a carbon nanotube surface in the presence of molecular dipoles such as the zwitterionic sarcosine amino acid. Full article

(This article belongs to the Special Issue Organic Macrocycles and Related Organic-Inorganic Hybrid Derivatives: Synthesis and Biological Applications)

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20 pages, 4211 KiB

Open AccessArticle

opp-Dibenzoporphyrin Pyridinium Derivatives as Potential G-Quadruplex DNA Ligands

by Nuno M. M. Moura, José A. S. Cavaleiro, Maria Graça P. M. S. Neves and Catarina I. V. Ramos

Molecules 2023, 28(17), 6318; https://doi.org/10.3390/molecules28176318 - 29 Aug 2023

Cited by 1 | Viewed by 1038

Abstract

Since the occurrence of tumours is closely associated with the telomerase function and oncogene expression, the structure of such enzymes and genes are being recognized as targets for new anticancer drugs. The efficacy of several ligands in telomerase inhibition and in the regulation [...] Read more.

Since the occurrence of tumours is closely associated with the telomerase function and oncogene expression, the structure of such enzymes and genes are being recognized as targets for new anticancer drugs. The efficacy of several ligands in telomerase inhibition and in the regulation of genes expression, by an effective stabilisation of G-quadruplexes (G4) DNA structures, is being considered as a promising strategy in cancer therapies. When evaluating the potential of a ligand for telomerase inhibition, the selectivity towards quadruplex versus duplex DNA is a fundamental attribute due to the large amount of double-stranded DNA in the cellular nucleus. This study reports the evaluated efficacy of three tetracationic opp-dibenzoporphyrins, a free base, and the corresponding zinc(II) and nickel(II) complexes, to stabilise G4 structures, namely the telomeric DNA sequence (AG₃(T₂AG₃)₃). In order to evaluate the selectivity of these ligands towards G4 structures, their interaction towards DNA calf thymus, as a double-strand DNA sequence, were also studied. The data obtained by using different spectroscopic techniques, such as ultraviolet-visible, fluorescence, and circular dichroism, suggested good affinity of the free-base porphyrin and of its zinc(II) complex for the considered DNA structures, both showing a pattern of selectivity for the telomeric G4 structure. A pattern of aggregation in aqueous solution was detected for both Zn(II) and Ni(II) metallo dibenzoporphyrins and the ability of DNA sequences to induce ligand disaggregation was observed. Full article

(This article belongs to the Special Issue Organic Macrocycles and Related Organic-Inorganic Hybrid Derivatives: Synthesis and Biological Applications)

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13 pages, 3482 KiB

Open AccessArticle

Synthesis and Characterization of Bulky Substituted Hemihexaphyrazines Bearing 2,6-Diisopropylphenoxy Groups

by Evgenii N. Ivanov, Verónica Almeida-Marrero, Oskar I. Koifman, Viktor V. Aleksandriiskii, Tomas Torres and Mikhail K. Islyaikin

Molecules 2023, 28(15), 5740; https://doi.org/10.3390/molecules28155740 - 29 Jul 2023

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Abstract

New substituted [30]trithiadodecaazahexaphyrines (hemihexaphyrazines) were synthesized by a crossover condensation of 2,5-diamino-1,3,4-thiadiazole with 4-chloro-5-(2,6-diisopropylphenoxy)- or 4,5-bis-(2,6-diisopropylphenoxy)phthalonitriles. The compounds were characterized by ¹H-, ¹³C-NMR, including COSY, HMBC, and HSQC spectroscopy, MALDI TOF spectrometry, elemental analysis, IR and UV-Vis absorbance and fluorescence techniques. Full article

(This article belongs to the Special Issue Organic Macrocycles and Related Organic-Inorganic Hybrid Derivatives: Synthesis and Biological Applications)

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16 pages, 2247 KiB

Open AccessArticle

DNA-Interactive and Damage Study with meso-Tetra(2-thienyl)porphyrins Coordinated with Polypyridyl Pd(II) and Pt(II) Complexes

by Bernardo Almeida Iglesias, Níckolas Pippi Peranzoni, Sophia Iwersen Faria, Luana Belo Trentin, André Passaglia Schuch, Otávio Augusto Chaves, Renan Ribeiro Bertoloni, Sofia Nikolaou and Kleber Thiago de Oliveira

Molecules 2023, 28(13), 5217; https://doi.org/10.3390/molecules28135217 - 5 Jul 2023

Cited by 2 | Viewed by 2112

Abstract

We report the DNA-binding properties of three porphyrins with peripheral thienyl substituents (TThPor, PdTThPor and PtTThPor). The binding capacity of each porphyrin with DNA was determined by UV-Vis and steady-state fluorescence emission spectroscopy combined with molecular docking calculations. The results [...] Read more.

We report the DNA-binding properties of three porphyrins with peripheral thienyl substituents (TThPor, PdTThPor and PtTThPor). The binding capacity of each porphyrin with DNA was determined by UV-Vis and steady-state fluorescence emission spectroscopy combined with molecular docking calculations. The results suggest that the interaction of these compounds probably occurs via secondary interactions via external grooves (minor grooves) around the DNA macromolecule. Moreover, porphyrins containing peripheral Pd(II) or Pt(II) complexes (PdTThPor and PtTThPor) were able to promote photo-damage in the DNA. Full article

(This article belongs to the Special Issue Organic Macrocycles and Related Organic-Inorganic Hybrid Derivatives: Synthesis and Biological Applications)

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17 pages, 2901 KiB

Open AccessArticle

A Remarkable Difference in Pharmacokinetics of Fluorinated Versus Iodinated Photosensitizers Derived from Chlorophyll-a and a Direct Correlation between the Tumor Uptake and Anti-Cancer Activity

by Taur Prakash Pandurang, Joseph Cacaccio, Farukh A. Durrani, Mykhaylo Dukh, Ajyal Z. Alsaleh, Munawwar Sajjad, Francis D’Souza, Dalip Kumar and Ravindra K. Pandey

Molecules 2023, 28(9), 3782; https://doi.org/10.3390/molecules28093782 - 27 Apr 2023

Cited by 2 | Viewed by 1520

Abstract

To investigate and compare the pharmacokinetic profile and anti-cancer activity of fluorinated and iodinated photosensitizers (PSs), the 3-(1′-(o-fluorobenzyloxy)ethyl pyropheophorbide and the corresponding meta-(m-) and para (p-) fluorinated analogs (methyl esters and carboxylic acids) were synthesized. Replacing iodine [...] Read more.

To investigate and compare the pharmacokinetic profile and anti-cancer activity of fluorinated and iodinated photosensitizers (PSs), the 3-(1′-(o-fluorobenzyloxy)ethyl pyropheophorbide and the corresponding meta-(m-) and para (p-) fluorinated analogs (methyl esters and carboxylic acids) were synthesized. Replacing iodine with fluorine in PSs did not make any significant difference in fluorescence and singlet oxygen (a key cytotoxic agent) production. The nature of the delivery vehicle and tumor types showed a significant difference in uptake and long-term cure by photodynamic therapy (PDT), especially in the iodinated PS. An unexpected difference in the pharmacokinetic profiles of fluorinated vs. iodinated PSs was observed. At the same imaging parameters, the fluorinated PSs showed maximal tumor uptake at 2 h post injection of the PS, whereas the iodinated PS gave the highest uptake at 24 h post injection. Among all isomers, the m-fluoro PS showed the best in vivo anti-cancer activity in mice bearing U87 (brain) or bladder (UMUC3) tumors. A direct correlation between the tumor uptake and PDT efficacy was observed. The higher tumor uptake of m-fluoro PS at two hours post injection provides a solid rationale for developing the corresponding ¹⁸F-agent (half-life 110 min only) for positron imaging tomography (PET) of those cancers (e.g., bladder, prostate, kidney, pancreas, and brain) where ¹⁸F-FDG-PET shows limitations. Full article

(This article belongs to the Special Issue Organic Macrocycles and Related Organic-Inorganic Hybrid Derivatives: Synthesis and Biological Applications)

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16 pages, 6185 KiB

Open AccessFeature PaperArticle

Four Routes to 3-(3-Methoxy-1,3-dioxopropyl)pyrrole, a Core Motif of Rings C and E in Photosynthetic Tetrapyrroles

by Khiem Chau Nguyen, Anh Thu Nguyen Tran, Pengzhi Wang, Shaofei Zhang, Zhiyuan Wu, Masahiko Taniguchi and Jonathan S. Lindsey

Molecules 2023, 28(3), 1323; https://doi.org/10.3390/molecules28031323 - 30 Jan 2023

Cited by 3 | Viewed by 1827

Abstract

The photosynthetic tetrapyrroles share a common structural feature comprised of a β-ketoester motif embedded in an exocyclic ring (ring E). As part of a total synthesis program aimed at preparing native structures and analogues, 3-(3-methoxy-1,3-dioxopropyl)pyrrole was sought. The pyrrole is a precursor to [...] Read more.

The photosynthetic tetrapyrroles share a common structural feature comprised of a β-ketoester motif embedded in an exocyclic ring (ring E). As part of a total synthesis program aimed at preparing native structures and analogues, 3-(3-methoxy-1,3-dioxopropyl)pyrrole was sought. The pyrrole is a precursor to analogues of ring C and the external framework of ring E. Four routes were developed. Routes 1–3 entail a Pd-mediated coupling process of a 3-iodopyrrole with potassium methyl malonate, whereas route 4 relies on electrophilic substitution of TIPS-pyrrole with methyl malonyl chloride. Together, the four routes afford considerable latitude. A long-term objective is to gain the capacity to create chlorophylls and bacteriochlorophylls and analogues thereof by facile de novo means for diverse studies across the photosynthetic sciences. Full article

(This article belongs to the Special Issue Organic Macrocycles and Related Organic-Inorganic Hybrid Derivatives: Synthesis and Biological Applications)

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Review

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27 pages, 5738 KiB

Open AccessReview

Recent Synthetic Advances on the Use of Diazo Compounds Catalyzed by Metalloporphyrins

by Mário M. Q. Simões, José A. S. Cavaleiro and Vitor F. Ferreira

Molecules 2023, 28(18), 6683; https://doi.org/10.3390/molecules28186683 - 18 Sep 2023

Viewed by 1440

Abstract

Diazo compounds are organic substances that are often used as precursors in organic synthesis like cyclization reactions, olefinations, cyclopropanations, cyclopropenations, rearrangements, and carbene or metallocarbene insertions into C−H, N−H, O−H, S−H, and Si−H bonds. Typically, reactions from diazo compounds are catalyzed by transition [...] Read more.

Diazo compounds are organic substances that are often used as precursors in organic synthesis like cyclization reactions, olefinations, cyclopropanations, cyclopropenations, rearrangements, and carbene or metallocarbene insertions into C−H, N−H, O−H, S−H, and Si−H bonds. Typically, reactions from diazo compounds are catalyzed by transition metals with various ligands that modulate the capacity and selectivity of the catalyst. These ligands can modify and enhance chemoselectivity in the substrate, regioselectivity and enantioselectivity by reflecting these preferences in the products. Porphyrins have been used as catalysts in several important reactions for organic synthesis and also in several medicinal applications. In the chemistry of diazo compounds, porphyrins are very efficient as catalysts when complexed with low-cost metals (e.g., Fe and Co) and, therefore, in recent years, this has been the subject of significant research. This review will summarize the advances in the studies involving the field of diazo compounds catalyzed by metalloporphyrins (M−Porph, M = Fe, Ru, Os, Co, Rh, Ir) in the last five years to provide a clear overview and possible opportunities for future applications. Also, at the end of this review, the properties of artificial metalloenzymes and hemoproteins as biocatalysts for a broad range of applications, namely those concerning carbene-transfer reactions, will be considered. Full article

(This article belongs to the Special Issue Organic Macrocycles and Related Organic-Inorganic Hybrid Derivatives: Synthesis and Biological Applications)

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94 pages, 27725 KiB

Open AccessReview

Tolyporphins–Exotic Tetrapyrrole Pigments in a Cyanobacterium—A Review

by Kathy-Uyen Nguyen, Yunlong Zhang, Qihui Liu, Ran Zhang, Xiaohe Jin, Masahiko Taniguchi, Eric S. Miller and Jonathan S. Lindsey

Molecules 2023, 28(16), 6132; https://doi.org/10.3390/molecules28166132 - 18 Aug 2023

Cited by 1 | Viewed by 1251

Abstract

Tolyporphins were discovered some 30 years ago as part of a global search for antineoplastic compounds from cyanobacteria. To date, the culture HT-58-2, comprised of a cyanobacterium–microbial consortium, is the sole known producer of tolyporphins. Eighteen tolyporphins are now known—each is a free [...] Read more.

Tolyporphins were discovered some 30 years ago as part of a global search for antineoplastic compounds from cyanobacteria. To date, the culture HT-58-2, comprised of a cyanobacterium–microbial consortium, is the sole known producer of tolyporphins. Eighteen tolyporphins are now known—each is a free base tetrapyrrole macrocycle with a dioxobacteriochlorin (14), oxochlorin (3), or porphyrin (1) chromophore. Each compound displays two, three, or four open β-pyrrole positions and two, one, or zero appended C-glycoside (or –OH or –OAc) groups, respectively; the appended groups form part of a geminal disubstitution motif flanking the oxo moiety in the pyrroline ring. The distinct structures and repertoire of tolyporphins stand alone in the large pigments-of-life family. Efforts to understand the cyanobacterial origin, biosynthetic pathways, structural diversity, physiological roles, and potential pharmacological properties of tolyporphins have attracted a broad spectrum of researchers from diverse scientific areas. The identification of putative biosynthetic gene clusters in the HT-58-2 cyanobacterial genome and accompanying studies suggest a new biosynthetic paradigm in the tetrapyrrole arena. The present review provides a comprehensive treatment of the rich science concerning tolyporphins. Full article

(This article belongs to the Special Issue Organic Macrocycles and Related Organic-Inorganic Hybrid Derivatives: Synthesis and Biological Applications)

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12 pages, 3164 KiB

Open AccessReview

Amino Acid Derivatives of Chlorin-e₆—A Review

by Maria da Graça H. Vicente and Kevin M. Smith

Molecules 2023, 28(8), 3479; https://doi.org/10.3390/molecules28083479 - 14 Apr 2023

Cited by 4 | Viewed by 1405

Abstract

Details of the structural elucidation of the clinically useful photodynamic therapy sensitizer NPe6 (15) are presented. NPe6, also designated as Laserphyrin, Talaporfin, and LS-11, is a second-generation photosensitizer derived from chlorophyll-a, currently used in Japan for the treatment of human lung, [...] Read more.

Details of the structural elucidation of the clinically useful photodynamic therapy sensitizer NPe6 (15) are presented. NPe6, also designated as Laserphyrin, Talaporfin, and LS-11, is a second-generation photosensitizer derived from chlorophyll-a, currently used in Japan for the treatment of human lung, esophageal, and brain cancers. After the initial misidentification of the structure of this chlorin-e₆ aspartic acid conjugate as (13), NMR and other synthetic procedures described herein arrived at the correct structure (15), confirmed using single crystal X-ray crystallography. Interesting new features of chlorin-e₆ chemistry (including the intramolecular formation of an anhydride (24)) are reported, allowing chemists to regioselectively conjugate amino acids to each available carboxylic acid on positions 13¹ (formic), 15² (acetic), and 17³ (propionic) of chlorin e₆ (14). Cellular investigations of several amino acid conjugates of chlorin-e₆ revealed that the 13¹-aspartylchlorin-e₆ derivative is more phototoxic than its 15²- and 17³-regioisomers, in part due to its nearly linear molecular conformation. Full article

(This article belongs to the Special Issue Organic Macrocycles and Related Organic-Inorganic Hybrid Derivatives: Synthesis and Biological Applications)

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