Chlorin e6 trimethyl ester
(Synonyms: 二氢卟吩 e6 三甲酯) 目录号 : GC68039Chlorin e6 trimethyl ester，是甲基脱镁叶绿酸-a 的衍生物，是一种可用于光动力疗法 (PDT) 的光敏剂。
Cas No.:35038-32-5
Sample solution is provided at 25 µL, 10mM.
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Quality Control & SDS
- View current batch:
- Purity: >99.00%
- COA (Certificate Of Analysis)
- SDS (Safety Data Sheet)
- Datasheet
Chlorin e6 trimethyl ester, a methyl pheophorbide-a derivative, is a photosensitizer that can be used in photodynamic therapy (PDT)[1][2].
Chlorin e6 trimethyl ester (5 mg/kg; i.p.) has no tumorcidal activity in mice[1].
[1]. Pandey RK, et, al. Chlorin and porphyrin derivatives as potential photosensitizers in photodynamic therapy. Photochemistry and Photobiology. 1991. 53(1):65-72.
[2]. Bauer D, et, al. Functionalization of chlorin e6 trimethylester towards potential amphiphilic photosensitizers for photodynamic therapy. Journal of Porphyrins and Phthalocyanines. 2019. 23(3): 243-250.
| Cas No. | 35038-32-5 | SDF | Download SDF |
| 别名 | 二氢卟吩 e6 三甲酯 | ||
| 分子式 | C37H42N4O6 | 分子量 | 638.75 |
| 溶解度 | DMSO : 10 mg/mL (15.66 mM; ultrasonic and warming and heat to 60°C) | 储存条件 | Store at -20°C |
| General tips | 请根据产品在不同溶剂中的溶解度选择合适的溶剂配制储备液；一旦配成溶液，请分装保存，避免反复冻融造成的产品失效。 储备液的保存方式和期限：-80°C 储存时，请在 6 个月内使用，-20°C 储存时，请在 1 个月内使用。 为了提高溶解度，请将管子加热至37℃，然后在超声波浴中震荡一段时间。 |
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| Shipping Condition | 评估样品解决方案：配备蓝冰进行发货。所有其他可用尺寸：配备RT，或根据请求配备蓝冰。 | ||
| 制备储备液 | |||
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1 mg | 5 mg | 10 mg |
| 1 mM | 1.5656 mL | 7.8278 mL | 15.6556 mL |
| 5 mM | 0.3131 mL | 1.5656 mL | 3.1311 mL |
| 10 mM | 0.1566 mL | 0.7828 mL | 1.5656 mL |
| 第一步：请输入基本实验信息（考虑到实验过程中的损耗，建议多配一只动物的药量） | ||||||||||
| 给药剂量 | mg/kg |  |
动物平均体重 | g | |
每只动物给药体积 | ul | |
动物数量 | 只 |
| 第二步：请输入动物体内配方组成（配方适用于不溶于水的药物；不同批次药物配方比例不同，请联系GLPBIO为您提供正确的澄清溶液配方） | ||||||||||
| % DMSO % % Tween 80 % saline | ||||||||||
| 计算重置 | ||||||||||
计算结果:
工作液浓度： mg/ml；
DMSO母液配制方法： mg 药物溶于 μL DMSO溶液（母液浓度 mg/mL，
体内配方配制方法：取 μL DMSO母液，加入 μL PEG300，混匀澄清后加入μL Tween 80，混匀澄清后加入 μL saline，混匀澄清。
1. 首先保证母液是澄清的；
2.
一定要按照顺序依次将溶剂加入，进行下一步操作之前必须保证上一步操作得到的是澄清的溶液，可采用涡旋、超声或水浴加热等物理方法助溶。
3. 以上所有助溶剂都可在 GlpBio 网站选购。
Synthesis of new chlorin e6 trimethyl and protoporphyrin IX dimethyl ester derivatives and their photophysical and electrochemical characterizations
Chemistry 2014 Oct 13;20(42):13644-55.PMID:25171181DOI:10.1002/chem.201403214.
In view of increasing demands for efficient photosensitizers for photodynamic therapy (PDT), we herein report the synthesis and photophysical characterizations of new Chlorin e6 trimethyl ester and protoporphyrin IX dimethyl ester dyads as free bases and Zn(II) complexes. The synthesis of these molecules linked at the β-pyrrolic positions to pyrano[3,2-c]coumarin, pyrano[3,2-c]quinolinone, and pyrano[3,2-c]naphthoquinone moieties was performed by using the domino Knoevenagel hetero Diels-Alder reaction. The α-methylenechromanes, α-methylenequinoline, and ortho-quinone methides were generated in situ from a Knoevenagel reaction of 4-hydroxycoumarin, 4-hydroxy-6-methylcoumarin, 4-hydroxy-N-methylquinolinone, and 2-hydroxy-1,4-naphthoquinone, respectively, with paraformaldehyde in dioxane. All the dyads as free bases and as Zn(II) complexes were obtained in high yields. All new compounds were fully characterized by 1D and 2D NMR techniques, UV/Vis spectroscopy, and HRMS. Their photophysical properties were evaluated by measuring the fluorescence quantum yield, the singlet oxygen quantum yield by luminescence detection, and also the triplet lifetimes were correlated by flash photolysis and intersystem crossing (ISC) rates. The fluorescence lifetimes were measured by a time-correlated single photon count (TCSPC) method, fluorescence decay associated spectra (FDAS), and anisotropy measurements. Magnetic circular dichroism (MCD) and circular dichroism (CD) spectra were recorded for one Zn(II) complex in order to obtain information, respectively, on the electronic and conformational states, and interpretation of these spectra was enhanced by molecular orbital (MO) calculations. Electrochemical studies of the Zn(II) complexes were also carried out to gain insights into their behavior for such applications.
[Evaluation of Photo- and Cytotoxicity of Chlorin e6 Ester Derivatives and Their Liposomal Forms]
Biofizika 2015 Sep-Oct;60(5):922-30.PMID:26591603doi
Photophysical characteristics and photosensitizing activity of the chlorin e6 dimethyl and trimethyl ester derivatives in various solution and their liposomal forms were studied. It was shown that in lipid vesicles chlorin e6 ester derivatives are predominantly in the monomeric state and possess optimal photophysical properties and high photochemical activity. The rate of redistribution of the chlorin e6 dimethyl ester from lipid vesicle to cells was higher as compared with that one of the Chlorin e6 trimethyl ester. The increase of the serum concentration in the incubation medium has a different effect on processes of accumulation of the liposomal forms of the chlorin e6 dimethyl and trimethyl ester derivatives by the cells. Cell culture studies showed that application of liposomal forms of the chlorin e6 dimethyl and trimethyl ester derivatives significantly decreases their cytotoxicity but keeps high cytotoxic effect of photodynamic activity of the chlorin e6 ester derivatives.
[Pharmacokinetics and tissue distribution characteristics of the novel photosensitizer 32-(4-methoxyphenyl)-152-aspartyl-chlorin e6]
Se Pu 2021 Dec;39(12):1291-1297.PMID:34812000DOI:10.3724/SP.J.1123.2021.01010.
Photodynamic therapy (PDT) has garnered immense research interest. PDT can directly kill the cells via a combination of photosensitizer, light, and molecular oxygen. It has emerged as a promising therapeutic option for cancer treatment owing to its advantages such as minimized systemic toxicity, minimal invasiveness, high therapeutic efficacy, and potential for developing antitumor immunity. The novel photosensitizer 32-(4-methoxyphenyl)-152-aspartyl-chlorin e6 (DYSP-C34) was synthesized by introducing a 32-aryl substitution and amino acid substituent of the Chenghai chlorin (CHC). Briefly, 32-(4-methoxyphenyl) substitution was achieved via olefin metathesis reactions. The aspartic acid side chain was introduced regioselectively at C-152, followed by hydrolysis to yield the target DYSP-C34. CHC with the same chemical structure as chlorin e6 was prepared from chlorophyll a, which was extracted from Spirulina powders derived from Chenghai Lake in the Yunnan province of China. This strategy successfully endowed the resultant photosensitizer with better cellular permeability and increased water solubility. In addition, the photodynamic antitumor effects of PDT largely depend on the dose of photosensitizer used, time between photosensitizer administration and light exposure, and possibly other still poorly known variables. Determination of optimal conditions for PDT requires a coordinated interdisciplinary effort. Therefore, the pharmacokinetics and tissue distribution of DYSP-C34 in vivo are critical for the efficacy and safety of PDT. Herein, a high performance liquid chromatography-ultraviolet (HPLC-UV) detection method was established for the determination of the new photosensitizer DYSP-C34 in rat plasma. The sample preparation involved a protein-precipitation and liquid-liquid extraction method. Methanol was used to precipitate proteins and chloroform was used to extract chlorins. Then, DYSP-C34 was separated on a Unitary C18 column (250 mm×4.6 mm, 5 μm) with a mobile phase comprising methanol and 5 mmol/L tetrabutylammonium phosphate buffer solution (70∶30, v/v). The flow rate was 1.0 mL/min with UV detection using a wavelength of 400 nm at 40 ℃. Results showed that DYSP-C34 and Chlorin e6 trimethyl ester (IS) were well separated under these conditions. The method was sensitive and sufficiently precise with a good linear relationship (determination coefficient (r2)=0.9941) over the range of 1-200 μg/mL in rat plasma. At three spiked levels (8, 40, and 120 μg/mL), the average recoveries were 74.39%, 69.71%, and 65.89%, respectively. The intra-day and inter-day relative standard deviations (RSDs) were lower than 5%. The precision met the requirements of biological sample determination. Furthermore, DYSP-C34 was stable in rat plasma under various storage conditions at room temperature, three freeze-thaw cycles, and long-term cryopreservation. The validated method was successfully applied to the pharmacokinetic study of DYSP-C34 after intravenous injection of a single dose in rat plasma. The pharmacokinetic parameters after intravenous injection of DYSP-C34 (16 mg/kg) were calculated. The plasma half-life (t1/2z) was 6.98 h, the area under the plasma concentration-time curve AUC(0-∞) was 1025.01 h·mg/L and the mean retention time MRT(0-∞) was 9.19 h. In addition, the results of DYSP-C34 distribution in tumor-bearing mice showed that DYSP-C34 could accumulate in tumor tissues, with higher concentrations in liver and kidney tissues, and lower concentrations in heart, spleen, and lung tissues. In summary, a specific, simple, and accurate HPLC-UV method was developed and validated for the determination of DYSP-C34 in rat plasma and tumor-bearing mouse tissues. The pharmacokinetics of DYSP-C34 after intravenous administration in rats and the tissue distribution characteristics of tumor-bearing mice were clarified for the first time. It is significant for clinical rational drug use and pharmacodynamic research. Therefore, choosing an appropriate time for light treatment time can achieve the best photodynamic effect. The results of pharmacokinetics and tissue distribution of DYSP-C34 provide vital guidance for subsequent pharmacodynamic research and further clinical trials in terms of dosage, light time, light toxicity and side effects.
Photochemistry of free and bound Zn-chlorophyll analogues to synthetic peptides depend on the quinone and pH
J Photochem Photobiol B 2015 Nov;152(Pt B):416-24.PMID:26232025DOI:10.1016/j.jphotobiol.2015.07.013.
A synthetic peptide was used as a scaffold to bind Zn-Chlorophyll (ZnChl) analogues through histidine ligation to study their photochemistry in the presence of different type of quinones. The Chl analogues were chlorin e6 (Ce6), Chlorin e6 trimethyl ester, pyropheophorbide a, and pheophorbide a while the quinones were PPBQ, DMBQ, NPHQ, DBTQ, DCBQ and PBQ. The binding of each ZnChl analogue to the peptide was verified by native gel electrophoresis. First the photo-stability of the ZnChl analogues were tested under continuous light. The ZnCe6 and ZnCe6TM analogues showed the least stability judged by the loss of optical signal intensity at their Qy band. The photoactivity of each ZnChl analogue was measured in the presence of each of the six quinones using time-resolved EPR spectroscopy. DMBQ was found to be the most efficient electron acceptor when all four ZnChl analogues were compared. The light-induced electron transfer between the ZnChl analogues complexed with the peptide and DMBQ were also measured using time-resolved EPR spectroscopy. The ZnCe6-peptide complex exhibited the highest photoactivity. The electron transfer in the complex was faster and the photoactivity yield was higher than those values obtained for free ZnCe6 and DMBQ. The fast phase of kinetics can be attributed to intra-protein electron transfer in the complex since it was not observed in the presence of DMBQ-glutathione adduct. Unlike free ZnCe6, the ZnCe6-peptide complex was robust and demonstrated very similar photoactivity efficiency in pH values 10, 8.0 and 5.0. The electron transfer kinetics were pH dependent and appeared to be modulated by the peptide charge and possibly fold. The charge recombination rate was slowed by an order of magnitude when the pH value was changed from 10.0 to 5.0. The implications of constructing the photoactive peptide complexes in terms of artificial photosynthesis are discussed.
Alkyl ether analogs of chlorophyll-a derivatives: Part 1. Synthesis, photophysical properties and photodynamic efficacy
Photochem Photobiol 1996 Jul;64(1):194-204.PMID:8787014DOI:10.1111/j.1751-1097.1996.tb02442.x.
The synthesis, preliminary in vivo biological activity, singlet oxygen and fluorescence yields of a series of alkyl ether derivatives of chlorophyll-alpha analogs are described. For short-chain carbon ethers (1-7 carbon units), it was observed that the biological activity increased by increasing the length of the carbon chain, being maximum in compounds with n-hexyl and n-heptyl chains. Related sensitizers prepared by reacting 2-(1-bromoethyl)-2-devinylpyropheophorbide-alpha with (sec)alcohols were found to be less effective. Under similar treatment conditions, photosensitizers containing cis- and trans- 3-hexenyl side chains were ineffective. Thus, both stereochemical and steric factors caused differences in sensitizing activity. In general, pyropheophorbide-alpha analogs were found to be more active than related chlorin e6 derivatives, in which the isocyclic ring (ring "E") was cleaved. Related photosensitizers in the 9-deoxy- series were found to be as effective as the corresponding pyropheophorbide-alpha analogs. The photosensitizers prepared from pyropheophorbide-alpha methyl ester and Chlorin e6 trimethyl ester have long wavelength absorption at 660 nm (epsilon 45 000 to 50 000). Reduction of the carbonyl group in the pyropheophorbide-alpha to methylene (ring E) resulted in a blue shift to 648 nm (epsilon 38 000).