Chlorophyll Derivatives Research Articles

Chlorophyll Inhibits the Digestion of Soybean Oil in Simulated Human Gastrointestinal System.

Nowadays, much available processed and highly palatable food such as cream products and fried and convenient food, which usually showed a high energy density, had caused an increase in the intake of dietary lipids, further leading to significant growth in the prevalence of obesity. Chlorophyll, widespread in fruits and vegetables, was proven to have beneficial effects on alleviating obesity. This study investigated the effects of chlorophyll on the digestive characteristics of lipids under in vitro simulated adult and infant gastrointestinal systems. Chlorophyll decreased the release rate of free fatty acid (FFA) during in vitro adult and infant intestinal digestion by 69.2% and 60.0%, respectively. Meanwhile, after gastrointestinal digestion, chlorophyll changed the FFA composition of soybean oil emulsion and increased the particle size of oil droplets. Interestingly, with the addition of chlorophyll, the activity of pancreatic lipase was inhibited during digestion, which may be related to pheophytin (a derivative of chlorophyll after gastric digestion). Therefore, the results obtained from isothermal titration calorimetry and molecular docking further elucidated that pheophytin could bind to pancreatic lipase with a strong affinity of (4.38 ± 0.76) × 107 M−1 (Ka), while the binding site was amino acid residue Trp253. The investigation not only explained why chlorophyll inhibited digestive enzyme activity to reduce lipids digestion but also provided exciting opportunities for developing novel chlorophyll-based healthy products for dietary application in preventing obesity.

Synthesis and evaluation of new pyropheophorbide-a derivatives for CAIX-targeted photodynamic therapy

A major challenge of photodynamic cancer therapy is to improve the selectivity of photosensitizers to the target pathological tissue. To overcome this issue, a series of chlorophyll derivatives containing thiadiazole sulfonamide moiety or 4-(2-aminoethyl)benzene sulfonamide moiety were designed and synthesized. These compounds showed intense absorption at 670 nm with high molar extinction coefficients, and strong fluorescence emission around 674 nm. Their singlet oxygen generation ability was also demonstrated to be excellent. They displayed obvious photo-cytotoxic effects to MDA-MB-231 cells in vitro and to tumor-bearing Balb/c nude mice in vivo. The fluorescence images exhibited that N-[2-((5-Sulfamoyl-1,3,4-thiadiazol-2-yl)amino)-2-oxoethyl]pyropheophorbide (AZ-Ppa-2) preferentially accumulated in MDA-MB-231 cell lines overexpressing CAIX (Carbonic anhydrase IX). Molecular Docking simulation revealed that AZ-Ppa-2 could closely bind to the active site residues of CAIX. Sub-organelle localization test indicated that AZ-Ppa-2 primarily localized in the lysosomes. These experiments suggested that AZ-Ppa-2, as a photosensitizer targeting CAIX, possessed an outstanding PDT anti-tumor effect with lasting regression of tumors, and deserved for further study.

New insights into chlorophyll-WSCP (water-soluble chlorophyll proteins) interactions : The case study of BnD22 (Brassica napus drought-induced 22 kDa)

The water-soluble chlorophyll-proteins (WSCP) of class II from Brassicaceae are non-photosynthetic proteins that bind chlorophylls (Chls) and chlorophyll derivatives. Their physiological roles, biochemical functions and mode of action are still unclear. It is assumed that the WSCPs have a protection function against Chl photodamage during stressful conditions. WSCPs are subdivided into class IIA and class IIB according to their apparent Chla/b binding ratio. Although their Chla/Chlb binding selectivity has been partly characterized, their Chl affinities are not yet precisely defined. For instance, WSCPs IIA do not show any Chl binding preference while WSCPs IIB have greater affinity to Chlb. In this study, we present a novel method for assessment of Chl binding to WSCPs based on the differences of Chl photobleaching rates in a large range of Chl/protein ratios. The protein we have chosen to study WSCP is BnD22, a WSCP IIA induced in the leaves of Brassica napus under water deficit. BnD22 formed oligomeric complexes upon binding to Chla and/or Chlb allowing a protective effect against photodamage. The binding constants indicate that BnD22 binds with high affinity the Chls and with a strong selectivity to Chla. Moreover, dependending of Chl/protein ratio upon reconstitution, two distinct binding events were detected resulting from difference of Chl stoichiometry inside oligomeric complexes.

Quasi-Bilayer All-Small-Molecule Solar Cells Based on a Chlorophyll Derivative and Non-Fullerene Materials with Untraditional Energy Alignments

Quasi-Bilayer All-Small-Molecule Solar Cells Based on a Chlorophyll Derivative and Non-Fullerene Materials with Untraditional Energy Alignments

Natural Chlorophyll Derivative Assisted Defect Passivation and Hole Extraction for MAPbI3 Perovskite Solar Cells with Efficiency Exceeding 20%

Natural Chlorophyll Derivative Assisted Defect Passivation and Hole Extraction for MAPbI₃ Perovskite Solar Cells with Efficiency Exceeding 20%

Chlorophyll derivative intercalation into Nb2C MXene for lithium-ion energy storage

Chlorophyll derivative intercalation into Nb2C MXene for lithium-ion energy storage

Intracellular bound chlorophyll residues identify 1 Gyr-old fossils as eukaryotic algae

The acquisition of photosynthesis is a fundamental step in the evolution of eukaryotes. However, few phototrophic organisms are unambiguously recognized in the Precambrian record. The in situ detection of metabolic byproducts in individual microfossils is the key for the direct identification of their metabolisms. Here, we report a new integrative methodology using synchrotron-based X-ray fluorescence and absorption. We evidence bound nickel-geoporphyrins moieties in low-grade metamorphic rocks, preserved in situ within cells of a ~1 Gyr-old multicellular eukaryote, Arctacellularia tetragonala. We identify these moieties as chlorophyll derivatives, indicating that A. tetragonala was a phototrophic eukaryote, one of the first unambiguous algae. This new approach, applicable to overmature rocks, creates a strong new proxy to understand the evolution of phototrophy and diversification of early ecosystems.

Chlorophyll derivative sensitized monolayer Ti3C2Tx MXene nanosheets for photocatalytic hydrogen evolution

Hydrogen production by photocatalytically splitting water is considered as a promising strategy for solar to chemical energy conversion to solve global energy problems. Ti3C2Tx is a two-dimensional transition metal titanium carbide material with excellent electrochemical properties. Nevertheless, the application of Ti3C2Tx as a co-catalyst in photocatalysis presents many challenges, which is mainly due to its lower photocatalytic activity. In this work, monolayer Ti3C2Tx nanosheets were prepared as efficient co-catalysts for the photocatalytic water splitting for H2 evolution through the delamination and exfoliation process of pristine two-dimensional titanium carbide Ti3C2Tx MXene. In addition, a chlorophyll-a derivative (Chl) was used as an effective visible light harvester by a simple one-step deposition process on monolayer Ti3C2Tx nanosheets, and a novel noble metal-free Chl@monolayer Ti3C2Tx photocatalyst was successfully synthesized for the photocatalytic water splitting to hydrogen evolution reaction (HER). It was found that the optimal Chl@monolayer Ti3C2Tx composite had the best HER performance as high as 106 μmol/h/gcat, which was much higher than that of the pristine Chl@Ti3C2Tx composite.

Bioprospecting of Less-Polar Fractions of Ericaria crinita and Ericaria amentacea: Developmental Toxicity and Antioxidant Activity.

Ericaria crinita and Ericaria amentacea from the Adriatic Sea (Croatia) were investigated with respect to the presence of less-polar compounds for the first time after fractionation by solid-phase extraction (SPE). The composition of less-polar fractions of freeze-dried E. crinita (FdEc) and E. amentacea (FdEa) were analyzed by high-performance liquid chromatography–high-resolution mass spectrometry with electrospray ionization (UHPLC-ESI-HRMS). The major identified compounds were: amides of higher aliphatic acids (palmitoleamide, linoleamide, palmitamide, oleamide and erucamide) and related compounds, carotenoid (fucoxanthin), chlorophyll derivatives (pheophytin a and b and their derivatives) and higher terpenes (loliolide, isoamijiol with its oxidation product), β-stigmasterol and (3β,6α)-14-methylergosta-8,24(28)-diene-3,6-diol). The toxic effects observed on the less-polar fractions obtained from Ericaria species on zebrafish Danio rerio embryos could be associated with the high abundance of all five detected amides. The antioxidant activity of the fractions was evaluated by means of five independent assays, including the reduction of the radical cation (ABTS), the oxygen radical absorbance capacity (ORAC), ferric-reducing antioxidant power (FRAP), the 2,2-diphenyl-1-picryl-hydrazyl (DPPH) assay and the Folin–Ciocalteu method. A higher antioxidant activity of E. amentacea in comparison to that of the E. crinita fractions was found with IC50 concentrations of 0.072 and 1.177 mg/mL, respectively. The correlation between the activity and the chemical composition revealed that the synergistic effect of different compounds impacted their antioxidant response.

Synthesis, dark and photoinduced cytotoxicity of 1-alkoxy-2-iodoethyl derivatives of chlorophyll a

Synthesis, dark and photoinduced cytotoxicity of 1-alkoxy-2-iodoethyl derivatives of chlorophyll a

A new megastigmane, known porphyrinic and galloylated bioactive derivatives from the leaves of Gymnosporia senegalensis

Investigation of the non-polar (rich in chlorophyll) and polar fractions of the ethyl acetate extract of Gymnosporia senegalensis (Lam.) Loes. leaves led to the isolation of nine compounds, including one new megastigmane derivative, (3 R*,5 S*,6 R*,7 E,9ξ)-7-megastigmene-3,6,9-triol-3- O-β-D-(6′- O-galloyl)glucopyranoside (1), four known galloylated derivatives (2, 3, 8, 9), three known chlorophyll derivatives (4–6), and one known fatty acid (7). The structures of the isolates were determined by means of spectroscopic and spectrometric data, as well as by comparison with literature values. The extracts and isolated compounds were tested for their antibacterial, antifungal, and antioxidant activities. The isolates showed weak to high antimicrobial activities with phaeophytin A (4) being the most active one whereas phaeophorbide-a (5) and Chlorine e6 trimethyl ester (6) exhibited the highest antioxidant activities.

Could chlorophyllins improve the safety profile of beta-d-N4-hydroxycytidine versus N-hydroxycytidine, the active ingredient of the SARS-CoV-2 antiviral molnupiravir?

Plain Language Summary Could natural plant pigment (chlorophyll) derivatives (chlorophyllins) improve the safety of the antiviral Molnupiravir, used to treat COVID-19 disease? Molnupiravir, a specific SARS-CoV-2 antiviral, may cause adverse genetic changes and thereby create potential host cell damage (through genotoxicity and DNA stressors). In our opinion, this side effect of treatment could be reduced if the antiviral was taken as a combined therapy with chlorophyllins. Specifically, we hypothesise that chlorophyllins might improve the overall effectiveness of molnupiravir, typically used to treat patients suffering from COVID-19. Chlorophyllins, antioxidants derived from natural plant chlorophyll, are safe, effective and non-toxic antioxidants that could combat possible genotoxic flow-on effects of molnupiravir. In addition, as they possess antiviral properties, treatment with chlorophyllins may enhance the overall antiviral effect via a mechanism different to molnupiravir.

Effects of different processing methods on the chlorophyll structure in kiwifruit.

Kiwifruit puree was treated with high and normal temperatures and pressures as independent variables to determinate the structural changes of chlorophyll derivatives. Two groups of colored elution samples were identified as single component compounds by High Performance Liquid Chromatography (HPLC). In addition, the structures of the two compounds were identified and analyzed by High Resolution Mass Spectrometry (HRMS) and Nuclear Magnetic Resonance (NMR). The results of HRMS and NMR demonstrate that components 1 and 2 were hydroxymethylbilane (HMB) and red chlorophyll catabolite (RCC), respectively, and indicate that HMB and RCC were the main pigments in the chlorophyll compounds after high temperature and pressure treatment. Furthermore, the cleavage pathway of the RCC in kiwifruit puree has been discussed, which provides a theoretical basis for the color protection of kiwifruit products in the course of processing.

Visible-light-induced hydrogen evolution from water on hybrid photocatalysts consisting of synthetic chlorophyll-a derivatives with a carboxy group in the 20-substituent adsorbed on semiconductors

Chlorophyll (Chl) derivatives have attracted much attention as photosensitizers in dye-sensitized solar cells. In contrast, only a few studies have been reported as Chl-based photosensitizers in photocatalytic hydrogen evolution from water, and therefore systematic studies should be required to obtain the optimal Chl photosensitizers for the photocatalytic water splitting system. In this study, we prepared four carboxylated Chl derivatives with different linkers at the 20-position, and investigated the effects of the linker length and π-conjugation between a chlorin macrocycle and a carboxy anchor. Hydrogen evolution rates on the Pt-loaded TiO2 adsorbing the Chl derivatives are significantly affected by the kind of linkers. The results indicated that (1) π-conjugation of a chlorin moiety with a carboxy anchor and (2) an appropriate linker length are of great importance to the photocatalytic activity probably due to the balance of electron injection to and back electron transfer from TiO2.

Chlorophyll derivatives/MXene hybrids for photocatalytic hydrogen evolution: Dependence of performance on the central coordinating metals

Development of efficient photocatalytic hydrogen evolution reaction (HER) with illumination of visible light is challenging. In this work, five chlorophyll derivatives (M-Chls; M = H2/Cu/Ni/Co/Zn) with different central ions in its cyclic tetrapyrrole ring including free base, copper, nickel, cobalt, and zinc were synthesized and employed as the effective visible-light harvester for efficient HER. In addition, two-dimensional (2D) noble metal-free co-catalyst Ti3C2Tx MXene was used as an excellent electron capturer due to its outstanding conductivity property. These M-Chls are modified on the surface of Ti3C2Tx MXene with 2D accordion-like morphology by means of a simple deposition process to form noble metal-free Chl/Ti3C2Tx-based photocatalysts for HER. It is found that the best HER performance as high as 49 μmol/h/gcat was achieved with the Co-Chl@Ti3C2Tx hybrid, which was much higher than those of other M-Chl@Ti3C2Tx composites. This research provides a specific way to synthesize low-cost and environmentally friendly natural Chls for developing highly efficient photocatalytic HER through molecular engineering.

Interactions of chlorophyll-derived photosensitizers with human serum albumin are determined by the central metal ion

Two structurally similar derivatives of chlorophyll a, chlorophyllide a (Chlide) and zinc-pheophorbide a (Zn-Pheide), differing only in central metal ion (Mg2+ or Zn2+, respectively) substituting the tetrapyrrole ring, were investigated with regard to their binding to human serum albumin (HSA). Chlide and Zn-Pheide are very promising photosensitizers with potential application in photodynamic therapy, therefore it is desirable to investigate their interactions with serum proteins. The studies included absorption and steady-state fluorescence spectroscopy, as well as molecular docking. It was found that both investigated compounds form complexes with HSA. Experimental data revealed two classes of binding sites for each compound. The affinities (Ka) for the first class were in the range of 105 and 106 M−1 for Chlide and Zn-Pheide, respectively, while the second class was characterized by the affinities of the order of 104 M−1 for both derivatives. Molecular docking simulations together with displacement studies revealed that the primary binding site of the studied compounds is the heme site, localized in the subdomain IB, however the best characterized binding sites of HSA, namely the Sudlow’s sites I and II are also involved. The interactions between the derivatives of chlorophyll and HSA were found to be predominantly hydrophobic and to a lesser extent hydrogen bonding. Our results demonstrate that the centrally bound metal ion determines both the affinity and mode of binding to HSA, which may be a feature differentiating these compounds in terms of their pharmacokinetics. Communicated by Ramaswamy H. Sarma

Synthesis and evaluation of new fluorinated pyropheophorbide-a derivatives for photodynamic therapy

The discovery of new photosensitizers with excellent photodynamic anti-tumor effects remains a challenge for photodynamic therapy and diagnosis. Here a series of chlorophyll derivatives containing fluorine-substituted alkyl side chain were designed and synthesized. These compounds exhibited strong absorption at 660–665 nm with excellent molar extinction coefficients. Their singlet oxygen generation ability was also proved to be excellent. Upon excitation with a 411 nm laser, strong fluorescence emission around 660–670 nm was observed. They also showed obvious photodynamic antitumor activity to A549 cell in vitro and to tumor-bearing mice in vivo. Their photodynamic anti-proliferative abilities were confirmed in vivo with histotomy. Flow cytometry test showed that new compounds could induce late period cell apoptosis or necrosis. Sub-organelle localization test indicated that they primarily localized in the endoplasmic reticulum. Among them, compound F-C4-Ppa possesses the most outstanding anti-tumor effect and therefore, it is a promising anti-tumor drug candidate in photodynamic therapy and photo-imaging diagnosis.

Green Plant Pigment, Chlorophyllin, Ameliorates Non-alcoholic Fatty Liver Diseases (NAFLDs) Through Modulating Gut Microbiome in Mice.

Non-alcoholic fatty liver diseases (NAFLDs) along with metabolic syndrome and Type-2 diabetes (T2D) are increasingly prevalent worldwide. Without an effective resolution, simple hepatic steatosis may lead to non-alcoholic steatohepatitis (NASH), characterized by hepatocyte damage, chronic inflammation, necrosis, fatty degeneration, and cirrhosis. The gut microbiome is vital for metabolic homeostasis. Conversely, dysbiosis contributes to metabolic diseases including NAFLD. Specifically, diet composition is critical for the enterotype of gut microbiota. We reasoned that green pigment rich in vegetables may modulate the gut microbiome for metabolic homeostasis. In this study, C57BL/6 mice under a high fat diet (HFD) were treated with sodium copper chlorophyllin (CHL), a water-soluble derivative of chlorophyll, in drinking water. After 28 weeks of HFD feeding, liver steatosis was established accompanied by gut microbiota dysbiosis, intestinal impairment, endotoxemia, systemic inflammation, and insulin resistance. Administration of CHL effectively alleviated systemic and intestinal inflammation and maintained tight junction in the intestinal barrier. CHL rebalanced gut microbiota in the mice under high fat feeding and attenuated hepatic steatosis, insulin resistance, dyslipidemia, and reduced body weight. Fecal flora transplants from the CHL-treated mice ameliorated steatosis as well. Thus, dietary green pigment or the administration of CHL may maintain gut eubiosis and intestinal integrity to attenuate systemic inflammation and relieve NASH.

Synthesis and photodynamic effect of 3-substituted methyl pyropheophorbide-a derivatives as novel photodynamic therapeutic agents for cancer treatment

The unique ability of chlorophyll derivatives to accumulate in tumor tissues and cause a photodynamic effect under laser radiation has been successfully used in photodynamic therapy (PDT). Previous research on modified peripheral substituents in chlorophyll showed that the presence and position of substituents in chlorin derivatives remarkably affect biological activities. Herein, we synthesized methyl pyropheophorbide-a (MPPa) derivatives, which are chlorophyll-a derivatives with heterocyclic aromatic substituents or pyrazole moieties on the peripheral positions. Then, we examined the PDT effects of these new derivatives in vitro and in vivo.

Knock down of NON-YELLOW COLOURING 1-like gene or chlorophyllin application enhanced chlorophyll accumulation with antioxidant roles in suppressing heat-induced leaf senescence in perennial ryegrass.

Loss of chlorophyll and oxidative damage co-occur during heat-induced leaf senescence. This study aimed to determine the functions of a chlorophyll catabolic gene, NON-YELLOW COLOURING 1 (NYC1)-like (NOL), in regulating heat-induced leaf senescence and to characterize antioxidant roles of a chlorophyll derivative, sodium copper chlorophyllin (SCC), in suppressing heat-induced leaf senescence. In two separate experiments, one by comparing NOL RNAi transgenic and wild-type plants, and the other by analysing the effects of SCC treatment, perennial ryegrass (Lolium perenne) was exposed to heat stress (38/35 °C, day/night) or optimal temperature (25/20 °C). Results showed that both knock down of LpNOL and application of SCC suppressed heat-induced leaf senescence, as manifested by increased chlorophyll content, reduced electrolyte leakage, down-regulation of chlorophyll-catabolic genes and senescence-related genes, as well as enhanced antioxidant capacity in the peroxidase pathway for H2O2 scavenging. Ex vivo SCC incubation protected membranes from H2O2 damage in mesophyll protoplasts of perennial ryegrass. The suppression of leaf senescence by knocking down NOL or chlorophyllin application was associated with enhanced chlorophyll accumulation playing antioxidant roles in protecting leaves from heat-induced oxidative damage.