Porphyrin Synthetic Methods for Bioorganic Applications

用于生物有机应用的卟啉合成方法

• 批准号: 7155556
• 负责人: JONATHAN SIDNEY LINDSEY
• 金额: $ 27.8万
• 依托单位: NORTH CAROLINA STATE UNIVERSITY RALEIGH
• 依托单位国家: 美国
• 财政年份: 1986
• 资助国家: 美国
• 起止时间: 1986-12-01 至 2007-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7155556
• 关键词: Address; Affect; Amines; Ammonium; Antibodies; Attention; Basic Science; Binding; Biological; Cells; Collaborations; Coupling; Deglutition; Depth; Development; Diagnostic; Environment; Esters; Family; Family member; Flow Cytometry; Foundations; Glycol; Glycols; Goals; Grant; Hand; Imagination; Imidates; Investigation; Isothiocyanates; Label; Lecithin; Light; Maleimides; Metals; Methanol; Methodology; Methods; Molecular; N-hydroxysuccinimide; Numbers; Organic solvent product; Penetration; Photochemistry; Porphyrins; Positioning Attribute; Property; Pyrroles; Range; Reagent; Research; Research Personnel; Route; Scientist; Solutions; Structure; Sulfhydryl Compounds; Tail; Tetrapyrroles; Therapeutic; Tissues; Ursidae Family; Water; Work; absorption; alkyl group; antibody conjugate; aqueous; bacteriochlorin; base; chlorin; cyanine dye; dehydrogenation; design; inorganic phosphate; insight; next generation; oxidation; physical property; prevent; programs; sound; water solubility

The long-term objective of this proposal is to develop synthetic methodology that can be used to gain deep insight into the biological properties of porphyrinic molecules and can be exploited in diagnostic and therapeutic applications. The term "porphyrinic" encompasses tetrapyrrole macrocycles that are fully unsaturated (porphyrins) or partially reduced (hydroporphyrins; such as chlorins or bacteriochlorins). The specific objective is to develop powerful routes for the synthesis of water-soluble, bioconjugatable porphyrins and hydroporphyrins. Hydroporphyrins absorb strongly in the red/near-IR spectral region, an ideal wavelength of light for deep penetration of cells and tissues. Such compounds are anticipated to have widespread biological applications where active targeting with a red/near-IR label is required, yet hydroporphyrins with the requisite molecular design features have not been available synthetically. The hydroporphyrins will bear one conjugatable handle, one or more water-solubilizing groups, structural features to prevent dehydrogenation and suppress oxidation, and tunable photochemistry via alteration of the centrally coordinated metal. Strategies for the rational synthesis of bacteriochlorins will be developed, including the derivatization of porphyrins, the derivatization of chlorins, and synthesis de novo. In the development of new synthetic routes, attention will be paid to issues of simplicity, scope, and scale, thereby enabling widespread utilization by a broad range of scientists from diverse fields. New molecular motifs will be investigated for achieving water solubility, a key requirement for use in biomolecule labeling studies. The basic science for the use of hydroporphyrin-biomolecule conjugates will be addressed by first characterizing the intrinsic properties of the hydroporphyrins, then characterizing the loading, non-covalent binding, aggregation, photostability, and brightness of hydroporphyrin-antibody conjugates. This work will open the door to applications such as multicolor/multiparameter labeling of cells and intracellular components, and provide a sound basis for the design and development of next-generation molecules for use in diverse therapeutic applications where active-targeting strategies are sought.

该提案的长期目标是开发合成方法，可用于深入了解卟啉分子的生物学特性，并可用于诊断和治疗应用。术语“卟啉”涵盖完全不饱和的(卟啉)或部分还原的(氢卟啉；例如二氢卟酚或菌绿素)的四吡咯大环。具体目标是开发合成水溶性、可生物共轭的卟啉和氢卟啉的强大途径。氢卟啉在红色/近红外光谱区域有强烈吸收，这是深度渗透细胞和组织的理想光波长。此类化合物预计将具有广泛的生物应用，其中需要红色/近红外标记的主动靶向，但具有必要的分子设计特征的氢卟啉尚未合成。氢卟啉将具有一个可共轭的手柄、一个或多个水溶性基团、防止脱氢和抑制氧化的结构特征，以及通过改变中心配位金属来调节光化学。将开发菌绿素的合理合成策略，包括卟啉衍生化、二氢卟酚衍生化和从头合成。在开发新的合成路线时，将关注简单性、范围和规模的问题，从而能够被不同领域的广泛科学家广泛利用。将研究新的分子基序以实现水溶性，这是生物分子标记研究中使用的关键要求。使用氢卟啉-生物分子缀合物的基础科学将通过首先表征氢卟啉的内在性质，然后表征氢卟啉-抗体缀合物的负载、非共价结合、聚集、光稳定性和亮度来解决。这项工作将为细胞和细胞内成分的多色/多参数标记等应用打开大门，并为下一代分子的设计和开发提供良好的基础，以用于寻求主动靶向策略的各种治疗应用。

项目成果

Progress Towards Synthetic Chlorins with Graded Polarity, Conjugatable Substituents, and Wavelength Tunability.

具有梯度极性、可共轭取代基和波长可调性的合成二氢卟酚的进展。

• DOI: 10.1142/s1088424615500042
• 发表时间: 2015
• 期刊: Journal of porphyrins and phthalocyanines
• 影响因子: 1.5
• 作者: Ra,Doyoung;Gauger,KellyA;Muthukumaran,Kannan;Balasubramanian,Thiagarajan;Chandrashaker,Vanampally;Taniguchi,Masahiko;Yu,Zhanqian;Talley,DanielC;Ehudin,Melanie;Ptaszek,Marcin;Lindsey,JonathanS
• 通讯作者: Lindsey,JonathanS

Hydrophilic tetracarboxy bacteriochlorins for photonics applications.

• DOI: 10.1039/c3ob41791c
• 发表时间: 2014-01
• 期刊: Organic & biomolecular chemistry
• 影响因子: 3.2
• 作者: J. Jiang;Pothiappan Vairaprakash;Kanumuri Ramesh Reddy;Tuba Sahin;M. Pavan;E. Lubian;J. Lindsey

Synthetic chlorins bearing auxochromes at the 3- and 13-positions.

在 3 位和 13 位带有助色团的合成二氢卟酚。

• DOI: 10.1021/jo060208o
• 发表时间: 2006
• 期刊: The Journal of organic chemistry
• 作者: Laha,JoydevK;Muthiah,Chinnasamy;Taniguchi,Masahiko;McDowell,BrianE;Ptaszek,Marcin;Lindsey,JonathanS
• 通讯作者: Lindsey,JonathanS

Extending the short and long wavelength limits of bacteriochlorin near-infrared absorption via dioxo- and bisimide-functionalization.

• DOI: 10.1021/jp512818g
• 发表时间: 2015-03
• 期刊: The journal of physical chemistry. B
• 作者: Pothiappan Vairaprakash;Eunkyung Yang;Tuba Sahin;M. Taniguchi;M. Krayer;J. Diers;Alfred Wang

In vitro photodynamic therapy and quantitative structure-activity relationship studies with stable synthetic near-infrared-absorbing bacteriochlorin photosensitizers.

• DOI: 10.1021/jm901908s
• 发表时间: 2010-05-27
• 期刊: JOURNAL OF MEDICINAL CHEMISTRY
• 影响因子: 7.3
• 作者: Huang, Ying-Ying;Mroz, Pawel;Zhiyentayev, Timur;Sharma, Sulbha K.;Balasubramanian, Thiagarajan;Ruzie, Christian;Krayer, Michael;Fan, Dazhong;Borbas, K. Eszter;Yang, Eunkyung;Kee, Hooi Ling;Kirmaier, Christine;Diers, James R.;Bocian, David F.;Holten, Dewey;Lindsey, Jonathan S.;Hamblin, Michael R.
• 通讯作者: Hamblin, Michael R.