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Chlorin
Chlorin
Chlorin
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Chlorin
Names
IUPAC name
2,3-Dihydroporphyrin [1]
Other names
2,3-Dihydroporphine
Identifiers
3D model (JSmol)
ChEBI
ChemSpider
  • InChI=1S/C20H16N4/c1-2-14-10-16-5-6-18(23-16)12-20-8-7-19(24-20)11-17-4-3-15(22-17)9-13(1)21-14/h1-6,9-12,22-23H,7-8H2/b13-9-,14-10-,15-9-,16-10-,17-11-,18-12-,19-11-,20-12- checkY
    Key: UGADAJMDJZPKQX-CEVVSZFKSA-N checkY
  • InChI=1/C20H16N4/c1-2-14-10-16-5-6-18(23-16)12-20-8-7-19(24-20)11-17-4-3-15(22-17)9-13(1)21-14/h1-6,9-12,22-23H,7-8H2/b13-9-,14-10-,15-9-,16-10-,17-11-,18-12-,19-11-,20-12-
    Key: UGADAJMDJZPKQX-CEVVSZFKBJ
  • C(N1)(/C=C2N=C(C=C\2)/C=C3N/C(C=C\3)=C\4)=CC=C1/C=C5CCC4=N/5
Properties
C20H16N4
Molar mass 312.36784
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
☒N verify (what is checkY☒N ?)

In organic chemistry, chlorins are tetrapyrrole pigments that are partially hydrogenated porphyrins.[2] The parent chlorin is an unstable compound which undergoes air oxidation to porphine.[3] The name chlorin derives from chlorophyll. Chlorophylls are magnesium-containing chlorins and occur as photosynthetic pigments in chloroplasts. The term "chlorin" strictly speaking refers to only compounds with the same ring oxidation state as chlorophyll.

Chlorins are excellent photosensitizing agents. Various synthetic chlorins analogues such as m-tetrahydroxyphenylchlorin (mTHPC) and mono-L-aspartyl chlorin e6 are effectively employed in experimental photodynamic therapy as photosensitizer.[4]

Chlorophylls

[edit]

The most abundant chlorin is the photosynthetic pigment chlorophyll. Chlorophylls have a fifth, ketone-containing ring unlike the chlorins. Diverse chlorophylls exists, such as chlorophyll a, chlorophyll b, chlorophyll d, chlorophyll e, chlorophyll f, and chlorophyll g. Chlorophylls usually feature magnesium as a central metal atom, replacing the two NH centers in the parent.[5]

Variation

[edit]
See also: Porphyrin § In nature
Structures comparing porphin, chlorin, bacteriochlorin, and isobacteriochlorin

Microbes produce two reduced variants of chlorin, bacteriochlorins and isobacteriochlorins. Bacteriochlorins are found in some bacteriochlorophylls; the ring structure is produced by Chlorophyllide a reductase (COR) reducing a chlorin ring at the C7-8 double boud.[6] Isobacteriochlorins are found in nature mostly as sirohydrochlorin, a biosynthetic intermediate of vitamin B12, produced without going through a chlorin. In living organisms, both are ultimately derived from uroporphyrinogen III, a near-universal intermediate in tetrapyrrole biosynthesis.[7]

Synthetic chlorins

[edit]

Numerous synthetic chlorins with different functional groups and/or ring modifications have been examined.[8]

Contracted chlorins can be synthesised by reduction of B(III)subporphyrin or by oxidation of corresponding B(III)subbacteriochlorin.[9] The B(III)subchlorins were directly synthesized as meso-ester B(III)subchlorin from meso-diester tripyrromethane, these class of compound showed very good fluorescence quantum yield and singlet oxygen producing efficiency[10][11]

See also

[edit]

Further reading

[edit]

References

[edit]
Revisions and contributorsEdit on WikipediaRead on Wikipedia

Chlorin

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Chlorin is a heterocyclic classified as a dihydroporphyrin, characterized by a macrocyclic structure consisting of four pyrrole-like rings connected by methine bridges, where one ring is reduced to a pyrroline unit via across the 2,3-double bond of the parent . Its molecular formula is C20H16N4, and the IUPAC name is 2,3-dihydroporphyrin, though the parent chlorin is an unstable, air-sensitive species that readily oxidizes to . In nature, chlorins form the chromophoric core of chlorophylls, magnesium complexes that enable light harvesting in across , , and , as well as certain bacteriochlorophylls (such as c, d, e, and f) in green sulfur bacteria and . The reduction of the ring imparts distinct photophysical properties, including a narrowed HOMO-LUMO gap that shifts absorption bands to longer wavelengths (typically 600–700 nm), facilitating efficient energy capture in the red to near-infrared region compared to the Soret and Q-bands of porphyrins. Synthetic chlorins, often prepared by derivatization of porphyrins through methods such as reduction, dihydroxylation followed by , or reactions, have been extensively developed since the early to mimic natural analogs and enhance stability. These derivatives exhibit tunable spectral properties influenced by substituents and ring conformation, making them valuable in applications like for cancer treatment, , and dye-sensitized solar cells due to their strong absorption, , and generation capabilities. Over 1,000 synthetic chlorins have been reported, spanning more than 50 structural motifs at the reduced pyrroline subunit, underscoring their versatility in bioinorganic and materials chemistry.

Chemical Structure and Properties

Core Molecular Structure

Chlorin is a classified as a partially hydrogenated , featuring four rings where one specific pyrrole unit is reduced by saturation of the 17,18-double bond, resulting in a dihydroporphyrin structure. The International Union of Pure and Applied Chemistry (IUPAC) designates it as 2,3-dihydroporphyrin, reflecting the saturation at positions 2 and 3 in the standardized parent numbering for the reduced ring. Its molecular formula is C₂₀H₁₆N₄, with a of 312.37 g/mol. The core structure consists of four rings (labeled A, B, C, and D) linked at their α-positions by four methine (=CH–) bridges, forming a planar , while the D imparts a non-aromatic character due to interrupted conjugation. Substituents in natural and synthetic chlorins are typically attached at the β-positions of the rings (carbons 2,3,7,8,12,13,17,18), enabling diverse functionalization while preserving the macrocyclic framework. This arrangement contrasts with fully conjugated systems, as the saturation disrupts the continuous π-system in the affected ring. The parent chlorin exhibits notable instability, readily undergoing air oxidation to porphine (the unsubstituted ), which underscores its tendency to revert to the more stable aromatic form under aerobic conditions. In comparison to , which possesses 22 π-electrons (18 delocalized in the aromatic system), chlorin contains 20 π-electrons due to the reduction, leading to reduced conjugation and altered electronic properties across the .

Physical Properties

Chlorins exhibit a or pigmentation attributable to their extended π-conjugation system, which imparts intense visible color to these macrocyclic compounds. These molecules demonstrate good in common organic solvents, including and acetone, facilitating their purification and handling in laboratory settings; however, unsubstituted chlorins possess limited in , a property that can be enhanced through peripheral substitutions such as sulfonation or . Spectroscopically, chlorins feature prominent absorption bands in the red portion of the , spanning approximately 650–700 nm, arising from the reduced symmetry of their altered 20 π-electron system compared to porphyrins; this results in high molar extinction coefficients exceeding 10^5 M⁻¹ cm⁻¹, making them effective for light-harvesting applications. Fluorescence quantum yields for chlorin derivatives typically reach up to 0.2 in polar organic solvents like DMF or DMSO. The parent chlorin structure is notably air-sensitive, readily undergoing oxidation to the corresponding upon exposure to oxygen, which underscores the need for inert handling conditions. Electrochemical reduction of the chlorin occurs at the periphery with potentials around -1.0 V versus the (SCE) in nonaqueous media, reflecting the electron-accepting nature of the .

Chemical Properties and Reactivity

Chlorins exhibit distinctive reactivity compared to fully aromatic porphyrins due to the reduced , which introduces a site of higher and facilitates specific transformations. One key reaction is the oxidation back to the , achieved through the loss of two hydrogens from the saturated C2–C3 bond in the reduced ring. This re-aromatization is readily catalyzed by exposure to air in solution or by chemical oxidants such as 2,3-dichloro-5,6-dicyano-1,4-benzoquinone (DDQ), often proceeding under mild conditions to yield the corresponding in high efficiency. Metalation of chlorins involves coordination of divalent metals at the central atoms, forming stable complexes that modify the electronic and steric properties of the . Common metals include Mg²⁺ and Zn²⁺, which insert via ligand exchange in solvents like or , often facilitated by bases or heat; these complexes, such as magnesium chlorins, mimic natural chlorophylls and exhibit altered potentials. The binding constants for such metalations typically fall in the range of 10⁶–10⁸ M⁻¹, reflecting strong affinity driven by the tetradentate N-donor ligation. The in chlorins increases local , enhancing reactivity toward electrophiles compared to porphyrins, with substitution often observed at meso-positions or activated β-sites. In acidic media, chlorins undergo at the two uncoordinated inner atoms, forming dicationic that alter the macrocycle's planarity and properties. This diprotonation occurs stepwise, with the pKₐ for the inner NH groups typically around 5–6, influenced by the reduced ring's electron-donating effect that slightly raises basicity compared to porphyrins. Chlorins display significant photoreactivity, particularly in the generation of singlet oxygen (¹O₂) upon visible light irradiation, owing to their efficient intersystem crossing to the triplet state. The quantum yield for singlet oxygen production (Φ_Δ) is approximately 0.5–0.7 for many unsubstituted or symmetrically substituted chlorins, making them potent photosensitizers; this process involves energy transfer from the excited triplet chlorin to ground-state oxygen.

Biological Occurrence and Role

In Chlorophyll and Photosynthesis

a serves as the primary photosynthetic in , , and , enabling the capture of energy essential for . Its molecular formula is C₅₅H₇₂MgN₄O₅, featuring a central magnesium coordinated within the chlorin macrocycle, a hydrophobic phytyl tail at the C17 propionate for anchoring, and a distinctive ring (ring V) attached at the C13² position, which contributes to its stability and spectral properties. This structure allows a to absorb strongly at approximately 430 nm in the and 662 nm in the , reflecting and imparting the characteristic color to photosynthetic tissues. Other chlorophyll variants, such as chlorophylls b, d, and f, share the core chlorin scaffold but differ in peripheral substituents, enhancing the spectral range of light absorption in photosynthetic organisms. Chlorophyll b features an aldehyde group (-CHO) at the C7 position instead of the methyl group found in chlorophyll a, shifting its absorption maxima to 453 nm and 642 nm and broadening the utilizable spectrum for energy capture. Chlorophyll d features a formyl group at the C3 position instead of the vinyl group found in chlorophyll a, with absorption peaks around 450 nm and 690 nm, while chlorophyll f features a formyl group at the C2 position instead of the methyl group found in chlorophyll a, absorbing maximally near 707 nm. All these chlorophylls share the core chlorin scaffold, biosynthetically formed by reduction of the porphyrin precursor to introduce the characteristic reduced pyrrole ring D, through subsequent modifications including metal insertion and esterification. In photosynthesis, chlorophyll molecules are integral to both antenna complexes and reaction centers, facilitating efficient light harvesting and . Within light-harvesting complexes like LHCII, hundreds of chlorophylls arranged in protein scaffolds absorb photons and transfer excitation energy via to the reaction centers with efficiencies exceeding 90%, minimizing energy loss. In (PSII), the specialized pair —composed of two molecules—absorbs light to initiate charge separation, oxidizing water and generating oxygen, while uses similar chlorophyll-based pairs for NADP⁺ reduction. This organization ensures rapid energy funneling from peripheral antennas to core reaction centers, supporting the high of oxygenic photosynthesis. The prevalence of chlorins in oxygenic reflects an evolutionary adaptation, as their D extends the Q-band absorption into the far-red region compared to porphyrins, allowing terrestrial to exploit diffuse more effectively under shaded or canopy conditions. This red-shift optimizes energy capture in environments where blue light is filtered out, providing a over earlier porphyrin-based systems in anoxygenic . Chlorophylls are typically extracted and isolated from thylakoid membranes using solvents like 80% acetone or , yielding approximately 1-2% of leaf dry weight, depending on and growth conditions; this disrupts membranes to release pigments for quantification and analysis.

Other Natural Chlorins

Beyond the well-known roles in oxygenic , chlorins serve diverse functions in and biosynthetic pathways. In anoxygenic phototrophs, such as , bacteriochlorophyll a functions as a key , featuring a bacteriochlorin core with an at the C3¹ position that contributes to its near-infrared absorption spectrum spanning 800-870 nm, enabling efficient light harvesting in low-light, anaerobic environments. This supports energy conversion in like Rhodopseudomonas species, where the integrates into light-harvesting complexes for quantum-efficient phototrophy under dim conditions. Sirohydrochlorin represents another critical natural isobacteriochlorin, a reduced acting as a biosynthetic intermediate in the production of siroheme and (cobalamin). Derived from uroporphyrinogen III through methylation at C2 and C7 followed by oxidation, sirohydrochlorin is an isobacteriochlorin bearing eight groups, which facilitate its role as a in enzymes like sulfite and reductases. This 's ferrochelation yields siroheme, essential for assimilatory across bacteria and , while its pathway diverges to support ring formation in B12 synthesis. Chlorophyllide, the de-phytylated derivative of , occurs naturally in and during early developmental stages of plants, serving as a transient intermediate in turnover and . In such as , chlorophyllide a arises from hydrolytic removal of the tail by chlorophyll dephytylase enzymes, aiding in repair and chlorophyll recycling under stress. Similarly, in higher plants, it accumulates briefly during phases, where re-phytylation by chlorophyll synthase restores full functionality for membrane integration. Chlorins also feature prominently in among green sulfur , where pigments like c, d, and e—structurally chlorins with meso-methylated rings—enable capture in deeply shaded, sulfidic aquatic niches. These , such as Chlorobium tepidum, house these chlorins in chlorosomes for efficient energy transfer, supporting autotrophic growth via oxidation without oxygen production. Additionally, chlorin derivatives contribute to cofactors in certain diazotrophic microbes, where sirohydrochlorin intermediates link tetrapyrrole metabolism to pathways. The evolutionary diversity of chlorins underscores their adaptability in extremophiles, particularly for absorption in niche habitats. In thermophilic and anaerobic extremophiles like nonsulfur , variants optimize near-IR harvesting (beyond 800 nm) for survival in low-light hydrothermal or sediment environments, reflecting ancient photosynthetic innovations predating oxygenic lineages. This spectral tuning, conserved across phyla like Chlorobiaceae, highlights chlorins' role in enabling phototrophy in extreme conditions such as high temperatures or chemical gradients.

Structural Variations

Isomers and Derivatives

Chlorins exhibit positional isomerism arising from the site of saturation in the . The chlorin is a 17,18-dihydroporphyrin, where the is reduced, leading to a characteristic asymmetry and red-shifted absorption compared to . Less common positional isomers include 7,8-dihydroporphyrins, in which the reduction occurs at the B ring beta positions (7,8) instead of the 17,18 positions, altering the electronic and synthetic ; these variants are typically accessed through targeted reductions of precursors. These non- positional isomers are less stable and rarely occur in nature, with synthetic access often challenging due to issues. Substitutional derivatives of the chlorin core expand its functional diversity through modifications at meso or beta positions. Chlorin e6, a key example, incorporates chains at the C13² and C15¹ positions of ring D, along with a at C3 on ring A, enhancing its amphiphilic nature for biomedical applications. Pheophorbide a, obtained by demetallation and hydrolysis of , retains the chlorin scaffold with a free-base core, a methoxycarbonyl at C13², and a at C17, making it a for design. Rhodochlorin, derived from chlorophyll degradation, features a 15¹-carboxylic acid substitution and an exocyclic ring modification on the standard chlorin scaffold, influencing its solubility and coordination behavior. These derivatives often arise from natural degradation pathways, with substitution patterns that briefly reference reactivity trends like altered potentials. The of chlorins centers on a predominantly planar , enabling efficient π-conjugation, though subtle ruffling distortions—alternating up-and-down displacements of beta carbons—can arise from peripheral steric crowding or metal coordination. Chiral centers in substituents, such as the (S) configuration at C13² and C15¹ in chlorophyll-derived chlorins, impart overall molecular without affecting the planarity directly. Naming conventions for chlorins build on the system, employing a standardized numbering from 1 to 20 for ring atoms and meso carbons at 5, 10, 15, and 20. Substituents on the isocyclic ring E are designated with superscripts and Greek letters (e.g., C13² for the beta position), as in chlorin p6, a trimethyl variant used in formulations. Variations in stability among chlorin isomers and derivatives are influenced by electronic effects; electron-withdrawing groups at beta positions (2,3,7,8,12,13,17,18) reduce electron density, thereby enhancing resistance to oxidative degradation. For example, beta-chlorination of meso-tetraphenylchlorins improves photooxidative stability by stabilizing the against attack. Bacteriochlorins represent a class of reduced distinguished from chlorins by the presence of two reduced rings located on opposite sides of the , typically at positions 7,8 and 17,18. This structural feature results in a tetrahydroporphyrin core with the molecular formula C₂₀H₁₈N₄. Unlike chlorins, which feature a single reduced ring, bacteriochlorins exhibit enhanced absorption in the near-infrared region, with characteristic bands between 700 and 800 nm, making them valuable for applications requiring deep tissue penetration of light. Isobacteriochlorins, a related subclass, feature reductions in two adjacent rings rather than opposite ones, leading to a distinct arrangement of saturated bonds. A prominent natural example is sirohydrochlorin, an isobacteriochlorin intermediate in corrinoid that serves as a cofactor in enzymes facilitating during sulfite and nitrite reduction. These non-opposite reductions alter the macrocycle's symmetry and electronic distribution compared to standard bacteriochlorins. The electronic properties of bacteriochlorins arise from their 18 π-electron , which supports an Q_y absorption band in the near-infrared due to lowered and altered orbital interactions relative to . This system also imparts a lower oxidation potential compared to chlorins, typically ~0.2 less positive, facilitating easier one-electron oxidation and enhancing their utility in redox-active processes. Bacteriochlorins generally display higher quantum yields than chlorins, often exceeding 0.2, owing to reduced non-radiative decay pathways, though their greater degree of reduction confers lower stability toward aerial oxidation, prone to dehydrogenation back to chlorin or porphyrin structures. Bacteriochlorins are synthetically accessible through of porphyrins, with (generated from and oxygen or other oxidants) serving as a mild that targets the β-pyrrole double bonds to yield the desired trans-reduced product in moderate to high yields. This method allows for the preparation of symmetrically substituted bacteriochlorins from readily available precursors, enabling further derivatization for tailored properties. Natural bacteriochlorophylls, such as those in photosynthetic , incorporate bacteriochlorin cores but with additional substituents that extend their absorption further into the near-infrared.

Biosynthesis and Synthesis

Biosynthetic Pathways

The biosynthesis of chlorins, the core macrocyclic structures in chlorophyll pigments, begins with the formation of δ-aminolevulinic acid (ALA), a committed precursor derived from and , though the pathway proper initiates from ALA itself. Two molecules of ALA are condensed by ALA dehydratase to form porphobilinogen (PBG). Four PBG units are then polymerized by PBG deaminase to hydroxymethylbilane, which uroporphyrinogen III synthase cyclizes and rearranges to uroporphyrinogen III, the first asymmetric intermediate. Uroporphyrinogen III undergoes sequential of its acetate side chains by uroporphyrinogen decarboxylase, effectively converting them to methyl groups and yielding coproporphyrinogen III. Oxidative of the propionate side chains on coproporphyrinogen III is catalyzed by coproporphyrinogen , producing protoporphyrinogen IX, which is then oxidized to by protoporphyrinogen . Chlorin formation diverges from the pathway at through the insertion of magnesium by magnesium chelatase, forming Mg-protoporphyrin IX, followed by at C13² and cyclization to create the isocyclic , yielding protochlorophyllide a. The critical reduction to the chlorin structure occurs via protochlorophyllide oxidoreductase (POR), which stereospecifically reduces the C17=C18 double bond in ring D of protochlorophyllide a to produce chlorophyllide a. This step transforms the fully conjugated system into the characteristic chlorin with a reduced . Subsequent esterification of chlorophyllide a with phytyl , catalyzed by chlorophyll synthase, yields , the primary chlorin-based pigment. Key enzymes in chlorin biosynthesis include uroporphyrinogen III synthase, which ensures the correct isomer formation early in the pathway, and magnesium chelatase, a heterotrimeric complex (subunits ChlD, ChlI, ChlH) that commits to the chlorophyll branch by inserting Mg²⁺ in an ATP-dependent manner. In plants, the POR-mediated reduction is light-dependent and functions under aerobic conditions, relying on protochlorophyllide as substrate accumulated in etioplasts. In contrast, many bacteria employ a dark-operative POR (DPOR), a nitrogenase-like complex that operates anaerobically without light. Regulation of chlorin biosynthesis in plants is tightly controlled, with light inducing the POR reaction to convert accumulated protochlorophyllide to chlorophyllide, preventing photooxidative damage during greening; this light dependency limits chlorophyll synthesis in dark-grown seedlings until illumination. The pathway yields approximately 10⁹ chlorophyll molecules per chloroplast in mature plant cells, reflecting high efficiency in thylakoid assembly. In bacterial variations, the pathway shares early steps but diverges in anaerobes where precorrin-2 methyltransferase (also known as uroporphyrinogen III methyltransferase) acts on uroporphyrinogen III to produce precorrin-2, which is further oxidized to sirohydrochlorin, an isobacteriochlorin intermediate that can branch toward synthesis or other tetrapyrroles like siroheme, adapting to low-oxygen environments.

Chemical Synthesis Methods

Chlorins, being partially reduced porphyrins, are commonly synthesized in the laboratory through of the corresponding precursors, enabling control over substitution patterns for targeted applications. Classical methods focus on the stereoselective addition of across one of the β,β'-double bonds in the . One established approach involves (OsO₄)-mediated of porphyrin N-oxides, followed by reduction of the resulting intermediates to yield chlorins; this method typically affords regioisomeric chlorins in combined yields of 50-70%, depending on the substituents. Alternatively, reduces porphyrins directly to chlorins under mild, solvent-free conditions, achieving representative yields of 50-70% for meso-aryl-substituted derivatives while minimizing over-reduction to bacteriochlorins. For the preparation of asymmetrically substituted chlorins, which are challenging to access via simple reductions, the dipyrromethane approach offers versatility. This method entails acid-catalyzed condensation of dipyrromethane units (derived from precursors) with aldehydes to form oligopyrromethene intermediates, followed by oxidative cyclization to a and selective reduction to the chlorin; it enables precise control over peripheral substituents and has been applied to synthesize stable, asymmetric chlorins in overall yields exceeding 20% from simple building blocks. A more recent strategy utilizes ring-contracted precursors like B(III) subporphyrins, which are reduced with p-toluenesulfonylhydrazide under basic conditions to generate meso-substituted subchlorins that can be further elaborated to full chlorins, or alternatively, oxidation of subbacteriochlorins provides access to the same scaffold. These transformations proceed in high yields (>80%) for meso-aryl chlorins, offering an efficient route to electronically tuned variants with reduced synthetic steps compared to traditional porphyrin-based methods. Post-2021 advancements have emphasized functionalization of existing chlorins to expand structural diversity. Palladium-catalyzed cross-coupling reactions, such as Suzuki-Miyaura couplings at β-positions enabled by prior borylation, allow selective introduction of aryl or alkyl groups on chlorin frameworks, facilitating the synthesis of multifunctional derivatives with yields up to 70% for β-substituted products. Additionally, streamlined total syntheses of biologically relevant chlorins like chlorin e6 have been reported, achieving the target in approximately 20 steps from achiral precursors through sequential dipyrromethane assembly and reduction, though semi-synthetic routes from natural sources remain more scalable for practical production. Purification of synthetic chlorins typically involves silica gel column chromatography under inert atmospheres (e.g., nitrogen or argon) to prevent air-induced oxidation back to porphyrins, with elution using hexane-ethyl acetate mixtures; this step is crucial as chlorins exhibit moderate stability but can form mixtures requiring careful fractionation to isolate pure isomers in >95% purity.

Applications

Photodynamic Therapy

In photodynamic therapy (PDT), synthetic chlorins serve as second-generation photosensitizers that, upon intravenous administration and subsequent illumination with red light, absorb photons at wavelengths typically between 650 and 690 nm to reach an excited triplet state, transferring energy to ground-state molecular oxygen to generate cytotoxic singlet oxygen (¹O₂) and other reactive oxygen species via Type II and Type I mechanisms, respectively. This oxidative stress induces apoptosis, necrosis, and vascular shutdown in targeted tumor cells while sparing surrounding healthy tissue due to selective light delivery. Chlorins accumulate preferentially in malignant tissues through the enhanced permeability and retention (EPR) effect, where leaky tumor vasculature facilitates their uptake and prolonged retention compared to normal cells. Prominent chlorin-based photosensitizers include temoporfin (mTHPC, marketed as Foscan®), a tetra(hydroxyphenyl)chlorin approved by the in 2001 for palliative treatment of advanced head and neck via intravenous injection at 0.15 mg/kg, followed by activation 96 hours later using a 652 nm delivering 2.5–5 J/cm². Temoporfin exhibits a terminal plasma of 65 hours, enabling effective tumor localization, with clinical trials demonstrating tumor response rates exceeding 80% in head and neck cancers and complete responses in up to 100% of early-stage lesions when combined with delivery. Another key compound is talaporfin sodium (Laserphyrin®), a chlorin e6 derivative approved in in 2015 for salvage PDT in locally recurrent after chemoradiotherapy, administered intravenously at 40 mg/m² and activated 4 hours later with a 664 nm at 100 J/cm², achieving an 88.5% complete response rate in phase II trials with minimal skin photosensitivity (0% incidence). Compared to first-generation porphyrin photosensitizers like porfimer sodium (Photofrin®), chlorins offer superior therapeutic profiles due to their intense absorption in the red spectral region (ε ≈ 30,000–50,000 M⁻¹ cm⁻¹ at 650–690 nm versus ~3,000 M⁻¹ cm⁻¹ at 630 nm for s), enabling deeper tissue penetration (up to 1–2 cm) and higher singlet oxygen quantum yields (0.4–0.8), alongside faster clearance from the body (photosensitivity lasting 2–4 weeks versus 4–6 weeks). As of 2025, clinical applications have expanded beyond initial approvals, with ongoing phase II/III trials evaluating chlorin e6-based formulations like Photolon for skin cancers (97.7% response rate in across 172 patients) and talaporfin for brain tumors such as gliomas, where median survival extends to 15–20 months in recurrent cases. Furthermore, chlorin-mediated PDT modulates the by releasing tumor antigens and stimulating immune responses, prompting investigations into combinations with , such as checkpoint inhibitors, to enhance abscopal effects in metastatic skin and brain cancers. Recent preclinical studies as of 2025 highlight the potential of nanocarrier-enhanced chlorins to improve delivery and efficacy in PDT.

Emerging Uses in Materials Science

Chlorins are gaining attention in photovoltaics as sensitizers in dye-sensitized solar cells (DSSCs), leveraging their intense absorption in the red to near-infrared (NIR) spectrum for enhanced light harvesting. A chlorin e6 derivative, modified with alkyl substituents and carboxylic acid anchoring groups, has achieved a power conversion efficiency of up to 6.7% under standard AM 1.5G conditions, highlighting the role of structural tuning in optimizing electron injection and charge recombination suppression. Zinc chlorins, in particular, surpass traditional porphyrin dyes in NIR response due to the reduced pyrrole ring that red-shifts the Q-band, enabling broader solar spectrum utilization and improved short-circuit current densities. In technologies, chlorins enable sensitive -based detection of through . A chlorin e6-copper(II) complex serves as a turn-off for Cu²⁺ with a of 0.212 μM (13.5 ppb) and restores for As(V) at 1.375 ppb, offering high selectivity in aqueous environments via specific binding to the macrocycle's and carboxyl sites. This mechanism, with binding constants exceeding 10⁵ M⁻¹, supports sub-ppm sensitivity suitable for of trace pollutants. Chlorins function as biomimetic catalysts in systems, mimicking natural complexes to drive CO₂ reduction. Fluorinated chlorin chromophores, paired with iron catalysts and sacrificial electron donors, achieve turnover numbers up to 1790 for CO production under red (630 nm), with initial turnover frequencies of 194 h⁻¹ and quantum yields around 0.88%. The process involves sequential two-electron reductions to form chlorinphlorin intermediates that efficiently transfer electrons to the catalyst, demonstrating over 240 hours of stable operation with >95% selectivity for CO from CO₂. Recent advancements address stability challenges in chlorin-based materials through hybridization with nanomaterials like . Few-layer -chlorin e6 hybrids exhibit improved photostability and dispersibility in aqueous media, enhancing durability for prolonged device operation without aggregation, as evidenced by maintained and structural integrity post-irradiation. These composites bridge synthetic tunability with robust scaffolds, paving the way for scalable applications in optoelectronic and catalytic devices.

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