Chlorophyll Derivatives Research Articles

Light‐Activated Biomedical Applications of Chlorophyll Derivatives

Back Cover: Chlorophyll derivatives can be extracted from plants, algae, and autotrophic microorganisms, and are gaining a lot of interest in nanotechnology. In fact, opportunely irradiated with light, they offer a multitude of photo-activated strategies for biomedical applications such as vision enhancement, optogenetics, antimicrobial and antitumor activities, and even generation of reactive oxygen species. This is reported by Carlotta Pucci, Chiara Martinelli, Andrea Degl'Innocenti, Andrea Desii, Daniele De Pasquale, and Gianni Ciofani in article number 2100181.

Climate change influences chlorophylls and bacteriochlorophylls metabolism in hypersaline microbial mat

This study aimed to determine the effect of the climatic change on the phototrophic communities of hypersaline microbial mats. Ocean acidification and warming were simulated alone and together on microbial mats placed into mesocosms. As expected, the temperature in the warming treatments increased by 4 °C from the initial temperature. Surprisingly, no significance difference was observed between the water pH of the different treatments despite of a decrease of 0.4 unit pH in the water reserves of acidification treatments. The salinity increased on the warming treatments and the dissolved oxygen concentration increased and was higher on the acidification treatments. A total of 37 pigments were identified belonging to chlorophylls, carotenes and xanthophylls families. The higher abundance of unknown chlorophyll molecules called chlorophyll derivatives was observed in the acidification alone treatment with a decrease in chlorophyll a abundance. This change in pigmentary composition was accompanied by a higher production of bound extracellular carbohydrates but didn't affect the photosynthetic efficiency of the microbial mats. A careful analysis of the absorption properties of these molecules indicated that these chlorophyll derivatives were likely bacteriochlorophyll c contained in the chlorosomes of green anoxygenic phototroph bacteria. Two hypotheses can be drawn from these results: 1/ the phototrophic communities of the microbial mats were modified under acidification treatment leading to a higher relative abundance of green anoxygenic bacteria, or 2/ the highest availability of CO2 in the environment has led to a shift in the metabolism of green anoxygenic bacteria being more competitive than other phototrophs.

Hydroquinone redox mediator enhances the photovoltaic performances of chlorophyll-based bio-inspired solar cells

Chlorophyll (Chl) derivatives have recently been proposed as photoactive materials in next-generation bio-inspired solar cells, because of their natural abundance, environmental friendliness, excellent photoelectric performance, and biodegradability. However, the intrinsic excitation dynamics of Chl derivatives remain unclear. Here, we show sub-nanosecond pump–probe time-resolved absorption spectroscopy of Chl derivatives both in solution and solid film states. We observe the formation of triplet-excited states of Chl derivatives both in deoxygenated solutions and in film samples by adding all-trans-β-carotene as a triplet scavenger. In addition, radical species of the Chl derivatives in solution were identified by adding hydroquinone as a cation radical scavenger and/or anion radical donor. These radical species (either cations or anions) can become carriers in Chl-derivative-based solar cells. Remarkably, the introduction of hydroquinone to the film samples enhanced the carrier lifetimes and the power conversion efficiency of Chl-based solar cells by 20% (from pristine 1.29% to 1.55%). This enhancement is due to a charge recombination process of Chl-A+/Chl-D–, which is based on the natural Z-scheme process of photosynthesis.

An Insight into Antioxidant and Antimicrobial Activities of Ethnotherapeutically Important Trans Himalayan Medicinal Plants: A Review

The high altitude of the Himalayan cold desert represents a valuable habitat of natural resources. The extreme climatic condition manifested by intense mutagenic UV-radiation, physiological drought, desiccation and strong winds, makes the survival of plants really difficult. As a consequence of this atmospheric stressor, the plants produce unique metabolites which play a preventive role in intrinsic mechanism of sustenance. Many plant species of this region have been investigated in search of novel antioxidants and antimicrobials. Plants synthesize several antioxidants that aid in antioxidant defense system, thereby protecting plants against damage caused by active ROS. These compounds include chlorophyll derivatives, alkaloids, essential oils, phytosterols, phenolics and polyphenolics. Some of the antioxidants that have been isolated from plants include curcumin, quercetin, ascorbic acid, resveratrol amongst many other compounds. Additionally, the emergence of resistance to multiple antimicrobial agents has become a major threat to public health. Hence, fresh efforts towards new drug identification and development are greatly needed. Plants have long been used in traditional Indian medicine for numerous therapeutic benefits and low toxicity. Considering the growing interest in quest for search of plant based antimicrobials and antioxidants; an effort has been carried to systematically record the antioxidants and antimicrobial potential of plants of Himalayan region.

Light-Activated Biomedical Applications of Chlorophyll Derivatives.

Tetrapyrroles are the basis of essential physiological functions in most living organisms. These compounds represent the basic scaffold of porphyrins, chlorophylls, and bacteriochlorophylls, among others. Chlorophyll derivatives, obtained by the natural or artificial degradation of chlorophylls, present unique properties, holding great potential in the scientific and medical fields. Indeed, they can act as cancer-preventing agents, antimutagens, apoptosis inducers, efficient antioxidants, as well as antimicrobial and immunomodulatory molecules. Moreover, thanks to their peculiar optical properties, they can be exploited as photosensitizers for photodynamic therapy and as vision enhancers. Most of these molecules, however, are highly hydrophobic and poorly soluble in biological fluids, and may display undesired toxicity due to accumulation in healthy tissues. The advent of nanomedicine has prompted the development of nanoparticles acting as carriers for chlorophyll derivatives, facilitating their targeted administration with demonstrated applicability in diagnosis and therapy. In this review, the chemical and physical properties of chlorophyll derivatives that justify their usage in the biomedical field, with particular regard to light-activated dynamics are described. Their role as antioxidants and photoactive agents are discussed, introducing the most recent nanomedical applications and focusing on inorganic and organic nanocarriers exploited in vitro and in vivo.

Synthesis of deuterated chlorophyll derivatives and their physical properties

The 3-vinyl group of methyl pyropheophorbide-a, one of the chlorophyll-a derivatives, was chemically transformed into partially or fully deuterated vinyl, 1-hydroxyethyl, acetyl, formyl, and hydroxymethyl groups via oxidation, oxidative cleavage, reduction, dehydration, or Grignard reaction. Using commercially available sodium borodeuteride and trideuteromethyl iodide as deuterium sources, a variety of regioselectively deuterated pyropheophorbides were obtained with either no or a slight loss of the deuteration degree compared with those of the starting deuterated materials. The deuteration affected largely the related infrared vibrational bands, slightly the chemical shifts of specific proton signals, and no change of visible absorption bands in a solution.

Aggregate-forming semi-synthetic chlorophyll derivatives / Ti3C2Tx MXene hybrids for photocatalytic hydrogen evolution

Chlorophylls (Chls) are the most abundant natural pigments having excellent opt-electrical and semi-conductive properties. Ti3C2Tx MXene, one of the most extensively studied 2D noble metal-free co-catalyst, features outstanding electrochemical properties. This work compares three aggregate-forming chlorophyll derivatives (Chl-n; n = 1–3), namely, zinc methyl 3-devinyl-3-hydroxymethyl-pyropheophorbide-a (Chl-1), zinc dodecyl 3-devinyl-3-hydroxymethyl-pyropheophorbide-a (Chl-2) and zinc dodecyl 131-deoxo-3-devinyl-131-dicyanomethylene-3-hydroxymethyl-pyropheophorbide-a (Chl-3), as light-harvesting antenna pigments in the MXene-based photocatalytic system for hydrogen evolution under the white light illumination (λ > 420 nm). The hydrogen evolution reaction (HER) of these Chls depends on the peripheral substituent groups at the C13- and/or C17-positions of the chlorin macrocyclic π-system. Differences among these Chl-n sensitized Ti3C2Tx MXene (Chl-n@Ti3C2Tx) are compared in terms of their light-harvesting ability, morphology, charge transfer efficiency and photocatalytic performance. The best HER performance is found to be as high as 122 μmol/h/gcat with the Chl-3@Ti3C2Tx composite. This work leads the direction in synthesizing Chls in Chl/MXene hybrid structure suitable for highly efficient photocatalytic HER.

Derivatives of Natural Chlorophylls as Agents for Antimicrobial Photodynamic Therapy.

The rapid growth of drug-resistant bacteria all over the world has given rise to a major research challenge, namely a search for alternative treatments to which bacteria will be unable to develop resistance. Photodynamic therapy is an approach of this kind. It involves the use of photosensitizers in combination with visible light at a certain wavelength to excite the former and generate reactive oxygen species. Various synthetic heterocyclic compounds are used as photosensitizers. Of these, derivatives of natural chlorophylls have a special place due to their properties. This review deals with the use of such compounds in antimicrobial PDT.

Visible Light-Induced Antibacterial Activity of Pigments Extracted from Dregs of Green and Black Teas.

Chlorophyll and its derivatives are potential natural sensitizers frequently applied in antimicrobial photodynamic therapy. Chlorophyll derivatives are formed naturally during tea processing, but they do not contribute to the color of tea infusions and thus are presumably left in the tea dregs. The present study aimed to investigate (i) the chlorophyll remnants in the pigments recovered from dregs of green and black teas and (ii) the antibacterial activity of pigments extracted from the tea dregs upon illumination using a light-emitting diode (LED) as the light source. Pigment analysis using high-performance liquid chromatography (HPLC) revealed the presence of main degradation products of chlorophylls, such as pheophytin and its epimers, pyropheophytin, and pheophorbides. In vitro assays demonstrated significant reductions in the number of viable bacteria in the presence of the pigments after 30 min of incubation with LED light irradiation. The descending order of bacterial susceptibility was Listeria monocytogenes > Staphylococcus aureus > Escherichia coli > Salmonella typhi. At an equivalent irradiation intensity, the blue and red LEDs could stimulate a comparable inactivation effect through photodynamic reactions. These findings demonstrated the valorization potential of tea dregs as a source of chlorophyll derivatives with visible light-induced antibacterial activity.

Late-Holocene palaeoenvironmental reconstruction from a lake in the Amazon Rainforest-Tropical Savanna (Cerrado) boundary in Brazil using a multi-proxy approach

As an ecotone, the region between the Amazon Rainforest and Tropical Savanna (Cerrado) biomes is, by definition, more susceptible to climate change. Therefore, understanding palaeoenvironmental dynamics is essential to address the future responses of such transition areas to climatic fluctuations. In this context, we present a new sediment record for the Late-Holocene retrieved from Barro-Preto, currently an oxbow lake located in an ecotone at the southern Brazilian Amazon border. Our multi-proxy data include carbon and nitrogen isotopes, as well as bulk TOC, chlorophyll derivatives, grain-size and microcharcoal analyses, all anchored on a radiocarbon-dated chronology. The sedimentary process recorded at the Barro-Preto Lake responded to both local and regional climate dynamics. It was influenced by river excursions associated to local responses to precipitation changes by the activation of the palaeochannel connecting the main-stem river and the Barro-Preto lake. This activation was evidenced by the presence of different colour lithology laminations accompanied by coarser sediments and also by climate conditions known to influence the Amazon region. Depositional processes linked to lake dynamics and different oxbow lake cycle stages were also important to explain the changes verified in the Barro-Preto record, endorsing the use of this lake formation for palaeoclimatic reconstructions. The record indicated a rising humidity trend, reflected by a progressive increase in lacustrine productivity, in accordance to other studies carried out in the Amazon region concerning the Late-Holocene, associated with a more southward displacement of the Intertropical Convergence Zone. Despite this rising humidity trend, dry episodic events during the Late-Holocene were evidenced by charcoal data, also coherent with regional Amazon studies, albeit exhibiting increased intensity, suggesting that the transitional nature of the environment might have influenced susceptibility to fires.

Conductivity of solution-processed films of a metal-free chlorophyll derivative: drop casting vs. spin coating

Conductivity of solution-processed films of a metal-free chlorophyll derivative: drop casting vs. spin coating

Synthesis of 20-substituted chlorophyll derivatives with F-ring and optical properties of their less distorted chlorin π-systems

Under acidic conditions, methyl bacteriopheophorbides-d bearing a variety of substituents at the 20-position were dehydrated in a 1-hydroxyethyl group at the 3-position to give methyl 20-substituted pyropheophorbides-a. In the same pot, the resulting 3-vinyl group was successively cyclized at the 5-position to afford the corresponding 3,5-ethano-chlorins as analogs of sedimentary porphyrins with two exo-five-membered rings. The 20-substitution is essential to the cyclization to produce the additionally fused F-ring. After the ring closure, the 20-bromine atom and acetyl group were removed by the action of the same acid to give the 20-unsubstituted product. The steric size of the 20-substituents affected the cyclization as well as the electronic absorption and emission of the 3,5-ethano-chlorins in a solution. The F-ring fusion suppressed the conformational distortion of the chlorin π-plane, partially regulating the optical properties: decrease of red shifts in Qy maxima by the 20-substitution and reduction of almost all Stokes shifts.

The Combination Effects of Immersion and Moderate Electric Field (MEF) Treatments on Enhancement of Deliverable Iron From Kale Leaves (Brassica oleracea L. Var. Sabellica)

Abstract Objectives Due to anti-nutrients found in leafy greens and the physical-chemical properties of inorganic iron found in plant sources, iron bioavailability is lower relative to heme iron rich in red meat. We tested a series of novel food processing techniques (i.e., vacuum treatment, bath-immersion, and moderate electric field (MEF) to improve iron content and potential delivery, using kale (Brassica oleracea L. var. sabellica) as our model green leafy vegetable. Methods A ferrous sulfate (FeSO4) solution was prepared and fresh kale samples (n = 3 per treatment) were immersed in the solution alone (control), treated with vacuum alone, vacuum + water bath (30–50°C), or vacuum + water bath + MEF (15 V/cm at frequency of 60 Hz at 40–60°C) for up to 15 min. Effects of immersion (24 h at 4°C) after each treatment step were also tested. Treated samples were rinsed in deionized water before freezing and lyophilization prior to analysis. Concentrations of chlorophyll and iron chlorophyll derivatives were measured in both lipophilic and polar leaf extracts using ultra high liquid chromatography-diode array detection (UHPLC-DAD). Atomic absorption spectrometry was used to measure iron concentrations. Differences between treatment groups were analyzed with one-way ANOVA, followed by Tukey's posthoc testing for pairwise comparisons (P < 0.05 considered statistically significant). Results Vacuum followed by immersion produced kale with ∼1500x more iron than the kale control, while MEF-treated kale had the greatest increase in iron concentration without immersion (∼4000x than control). Two novel metabolites, tentatively iron chlorophyllin derivatives, were observed in the lipophilic extracts of the MEF and immersed kale samples, and identifies are being pursued via UHPLC-high resolution mass spectrometry metabolomics. Conclusions The novel food processing techniques employed here produced kale with iron concentrations significantly higher than the kale control, as well as other iron-rich plant foods (e.g., ∼40x times higher than black beans). Future testing will determine if this” iron-enhanced” kale has the potential to better deliver iron as compared to untreated kale, an FeSO4 supplement, or a heme-rich source. Funding Sources This research was supported by OARDC via a SEEDS grant and also via Hatch #W4122.

Shengxuening Extracted from Silkworm Excrement Mitigates Myelosuppression via SCF-Mediated JAK2/STAT3 Signaling.

Shengxuening (SXN) is a Chinese patent medicine with main ingredients (including chlorophyll derivatives and sodium iron chlorophyllin) extracted from silkworm excrement. SXN exhibited efficacy in clinical trials of renal anemia and iron deficiency anemia; however, the specific mechanisms remain unclear. This study found that SXN increased the number of peripheral blood cells and improved the bone marrow morphology in myelosuppressed mouse model, reversed the reduction in body weight and spleen indices, and increased the serum levels of erythropoietin and granulocyte-macrophage colony-stimulating factor. Quantitative real-time PCR array and Western blot analysis showed the enhanced expression of stem cell factor (SCF), JAK2, and STAT3 in the liver. These results suggested that SXN promoted the recovery of hemopoietic function in myelosuppressed models by increasing the secretion of hematopoietic factors and activating the JAK2/STAT3 pathway. Therefore, this medicine may be applied as therapeutic pharmaceutical drug to mitigate myelosuppression.

The Origin, Physicochemical Properties, and Removal Technology of Metallic Porphyrins from Crude Oils

Crude oil is an indispensable energy feedstock for daily activities, although some amounts of metallic porphyrins components with undesired characteristics have been identified. These constituents are assumed to originate from the geochemical process of chlorophyll and heme derivatives. In addition, their chemical structures have been thoroughly characterized using spectroscopy techniques, while several analytical methods were adopted in the detection and concentration quantification in the crude oils. The metallic porphyrins have several demerits, including the deactivation of used catalysts, contamination of the treated petrochemical products, and corrosion of the industrial equipment. Also, the removal process is considered challenging due to the strong interaction with the asphaltene fraction of crude oil. This review article, therefore, provides brief information on the origin, physicochemical properties, and possible removal technology of metallic porphyrins from crude oil samples. Besides, a better understanding of chemistry contributes a useful insight towards the development and establishment of better futuristic processing technology.

Recovery of ascorbic acid, phenolic compounds and carotenoids from acerola by-products: An opportunity for their valorization

Ascorbic acid, phenolic compounds and carotenoids were extracted from acerola (Malpighia emarginata DC.) by-products using gas-expanded liquids (GXLs) based on carbon dioxide expanded ethanol at 40 °C and 7 MPa. The by-products generated in the processing of acerola: bagasse (seed and peel) and non-pomace (from the juice clarification step), were studied separately. The overall extraction yields obtained were 3.8 and 12.9 g/100 g for bagasse and non-pomace, respectively. Ascorbic acid was not detected in the bagasse extract, while 158.2 mg/gextract was found in non-pomace extract, and 193.7 mg/g was found in the acerola juice powder. The higher the concentration of ascorbic acid, the higher the antioxidant activity of the extracts. The phytochemical profile obtained by LC-Q-TOF-MS/MS showed a higher number of phenolic compounds (hydroxycinnamic acids and flavonoids) in the bagasse and non-pomace extracts when compared to acerola juice. In addition, GXL promoted the extraction of a pool of carotenoids (lutein and β-carotene), pheophytin and chlorophyll derivatives detected by LC-APCI-MS/MS. The obtained extracts, rich in bioactive compounds, open an opportunity for the valorization of acerola by-products, meeting the current demand for natural nutraceuticals rich in vitamin C and polyphenols.

Metabolite Profiling of Christia vespertilionis Leaf Metabolome via Molecular Network Approach

Christia vespertilionis (L.f.) Bakh. f. is an ornamental plant with unique butterfly-shaped leaves, hence its vernacular name “butterfly wing” or “rerama” in Malay. In Malaysia, the green-leafed variety of this plant has gained popularity in recent years due to testimonial reports by local consumers of its medicinal uses, which include treatment for cancer. Despite these popular uses, there is very limited information on the phytochemistry of the leaf of this plant, presenting a significant gap in the cheminformatics of the plant species. Herein, we report a substantially detailed phytochemical profile of the leaf metabolome of the green-leafed variety of C. vespertilionis, obtained by deploying an untargeted tandem mass spectrometry-based molecular networking approach. The detailed inspection of the molecular network map generated for the leaf metabolome enabled the putative identification of 60 metabolites, comprising 13 phenolic acids, 20 flavonoids, 2 benzyltetrahydroisoquinoline-type alkaloids, 4 hydroxyjasmonic acid derivatives, 2 phenethyl derivatives, 3 monoacylglycerols, 4 fatty acid amides, 2 chlorophyll derivatives, 4 carotenoids, 2 organic acids, 1 nucleoside, and 3 amino acids. Flavonoids are the major class of metabolites that characterize the plant leaves. Employing a mass-targeted isolation approach, two new derivatives of apigenin-6-C-β-glucoside, the major constituents of the plant leaf, were successfully purified and spectroscopically characterized as apigenin-6-C-β-glucoside 4′-O-α-apiofuranoside (28) and apigenin-6-C-β-[(4″,6″-O-dimalonyl)-glucoside] 4′-O-α-apiofuranoside (47). This work provides further information on the chemical space of the plant leaf, which is a prerequisite to further research towards its valorization as a potential phytopharmaceutical product.

ASSESSEMENT OF CHLOROPHYLL PHOTOTOXICITY ON HONEY BEE, APIS MELLIFERA (HYMENOPTERA: APIDAE).

This study evaluated the eco-toxicological parameters of two chlorophyll derivatives, copper chlorophyllin(Cu-chlorophyllin) and magnesium chlorophyllin (Mg-chlorophyllin) on viability of honeybee. Chlorophyll and its derivatives have a wide range of applications such as coloring in food additivesand photopesticide against medical and agricultural pests. The results of Cu-chlorophyllin andMg-chlorophyllin using different concentrations in honey bee's feeding bait indicated their efficiencyon honey bee's viability as a functionwas 10% within the range 10-6 -7x10-6 M/L and reached 25% at 10-5 M/L compared to 5% mortalityin control samples. The LC50 of both derivatives showed the Mg-chlorophyllin was less toxic thanCu-chlorophyllin on bee's viability. The maximum mortality was 14% & 21% for Mg-chlorophyllinand Cu-chlorophyllin respectively. Semi-field experiment revealed that the natural activity of honeybee workers outside the hive reduced the effect of chlorophyll derivatives on honey viability oflaboratory testing obtained data.

COVID-19 Therapy: Could a Copper Derivative of Chlorophyll a Be Used to Treat Lymphopenia Associated With Severe Symptoms of SARS-CoV-2 Infection?

OPINION article Front. Med., 12 March 2021Sec. Infectious Diseases – Surveillance, Prevention and Treatment Volume 8 - 2021 | https://doi.org/10.3389/fmed.2021.620175

Direct Assembly in Aqueous Solutions of Stable Chlorophyllide Complexes with Type II Water-soluble Chlorophyll Proteins.

Water-soluble chlorophyll-binding proteins (WSCPs) from Brassicaceae constitute a small family of non-photosynthetic proteins that may provide a useful benchmark and model system for studying molecular aspects of chlorophyll-protein interactions such as the tuning of absorption and emission spectra, and binding selectivity. WSCP apo-proteins are readily expressed by recombinant DNA techniques and can be assembled in vitro with natural and synthetic chlorophyll derivatives. The complexes with native chlorophylls are exceptionally stable toward thermal dissociation and protein denaturation due to hydrophobic interactions with the chlorophyll's phytyl chains that stabilize the core of the WSCP tetrameric complexes. However, assembly requires the use of detergents or water-in-oil emulsions to introduce the hydrophobic pigments into the water-soluble apo-proteins. Here, we explore the direct assembly of recombinant WSCPs with the water-soluble phytyl-free chlorophyll analogue chlorophyllide a in aqueous solutions. We show that the complexes formed by mixing chlorophyllide and WSCP apo-proteins are exclusively tetrameric, and while they lack the extreme thermostability of the respective chlorophyll complexes, they are still thermostable up to around 60°C. Their absorption and CD spectra are very similar to the chlorophyll complexes albeit slight peak shifts and broadening of the bands indicate variations in pigment and protein conformations, and less rigid structures. Simplifying the assembly process of WSCPs opens new possibilities for their use in modelling natural chlorophyll-protein complexes, and as templates for designing novel artificial protein-pigment complexes.