Publications by authors named "Jayeeta Bhaumik"

23 Publications

  • Page 1 of 1

Recent Advances in Functionalization of Pyrroles and their Translational Potential.

Chem Rec 2021 Apr 2;21(4):715-780. Epub 2021 Mar 2.

Department of Pharmaceutial Technology (Process Chemistry), National Institute of Pharmaceutical Education & Research (NIPER) S.A.S. Nagar, Mohali, 160062, India.

Among the known aromatic nitrogen heterocycles, pyrrole represents a privileged aromatic heterocycle ranging its occurrence in the key component of "pigments of life" to biologically active natural products to active pharmaceuticals. Pyrrole being an electron-rich heteroaromatic compound, its predominant functionalization is legendary to aromatic electrophilic substitution reactions. Although a few excellent reviews on the functionalization of pyrroles including the reports by Baltazzi in 1963, Casiraghi and Rassu in 1995, and Banwell in 2006 are available, they are fragmentary and over fifteen years old, and do not cover the modern aspects of catalysis. A review covering a comprehensive package of direct functionalization on pyrroles via catalytic and non-catalytic methods including their translational potential is described. Subsequent to statutory yet concise introduction, the classical functionalization on pyrroles using Lewis acids largely following an ionic mechanism is discussed. The subsequent discussion follows the various metal-catalyzed C-H functionalization on pyrroles, which are otherwise difficult to implement by Lewis acids. A major emphasize is given on the radical based pyrrole functionalization under metal-free oxidative conditions, which is otherwise poorly highlighted in the literature. Towards the end, the current development of pyrrole functionalization under photocatalyzed and electrochemical conditions is appended. Only a selected examples of substrates and important mechanisms are discussed for different methods highlighting their scopes and limitations. The aromatic nucleophillic substitution on pyrroles (being an electron-rich heterocycle) happened to be the subject of recent investigations, which has also been covered accentuating their underlying conceptual development. Despite great achievements over the past several years in these areas, many challenges and problems are yet to be solved, which are all discussed in summary and outlook.
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http://dx.doi.org/10.1002/tcr.202100010DOI Listing
April 2021

Co-administration of zinc phthalocyanine and quercetin via hybrid nanoparticles for augmented photodynamic therapy.

Nanomedicine 2021 Feb 3;33:102368. Epub 2021 Feb 3.

Department of Pharmaceutical Technology (Biotechnology), National Institute of Pharmaceutical Education and Research (NIPER), Sector-67, S.A.S. Nagar-160062, Punjab, India; Department of Biotechnology, National Institute of Pharmaceutical Education and Research (NIPER), Sector-67, S.A.S. Nagar-160062, Punjab, India. Electronic address:

The photodynamic anticancer activity of a photosensitizer can be further increased by co-administration of a flavonoid. However, this requires that both molecules must be effectively accumulated at the tumor site. Hence, in order to enhance the activity of zinc phthalocyanine (ZnPc, photosensitizer), it was co-encapsulated with quercetin (QC, flavonoid) in lipid polymer hybrid nanoparticles (LPNs) developed using biodegradable & biocompatible materials and prepared using a single-step nanoprecipitation technique. High stability and cellular uptake, sustained release, inherent fluorescence, of ZnPC were observed after encapsulation in the LPNs, which also showed a higher cytotoxic effect in breast carcinoma cells (MCF-7) compared to photodynamic therapy (PDT) alone. In vivo studies in tumor-bearing Sprague Dawley rats demonstrated that the LPNs were able to deliver ZnPc and QC to the tumor site with minimal systemic toxicity and increased antitumor effect. Overall, the photodynamic effect of ZnPc was synergized by QC. This strategy could be highly beneficial for cancer management in the future while nullifying the side effects of chemotherapy.
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http://dx.doi.org/10.1016/j.nano.2021.102368DOI Listing
February 2021

Development of a light activatable lignin nanosphere based spray coating for bioimaging and antimicrobial photodynamic therapy.

J Mater Chem B 2021 02 20;9(6):1592-1603. Epub 2021 Jan 20.

Department of Nanomaterials and Application Technology, Center of Innovative and Applied Bioprocessing (CIAB), Department of Biotechnology (DBT), Government of India, Sector 81 (Knowledge City), Punjab, India.

Many coating materials are commercially available to combat microbial infections. However, these coatings are difficult to synthesize, and are mostly composed of toxic chemicals. Lignin is an under-explored natural biopolymer with multifaceted potential. Lignin, with adhesive, UV resistant, and antimicrobial properties, is a suitable candidate to develop coating materials. Here we report a smart method to fabricate a sustainable nanospray coating from lignin which does not require any toxic chemicals or additives during synthesis. Initially, we have developed stable lignin nanospheres in a single step in aqueous medium, which were later utilized as a lignin nanospray (LNSR). The LNSR was characterized by dynamic light scattering, scanning electron microscopy, FTIR and other analytical techniques. This LNSR showed remarkable UV blocking, antioxidant and light-activated antimicrobial properties. Interestingly, for the first time, the LNSR demonstrated photoluminescence, making it useful for bioimaging. Moreover, singlet oxygen generation potential was observed in the LNSR, which could render it useful in phototheranostic applications (i.e. light assisted imaging and photodynamic therapy). Further, the LNSR was directly utilized to fabricate a sustainable coating. The nanospray coating exhibited maximum light-induced cell killing when applied to common microbes as detected by live-dead cell imaging. Taken together, the lignin nanospray coating developed via a direct pathway holds great promise to disinfect microbes in the presence of light.
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http://dx.doi.org/10.1039/d0tb02643cDOI Listing
February 2021

Recent progress in nanomaterial-based sensing of airborne viral and bacterial pathogens.

Environ Int 2021 01 25;146:106183. Epub 2020 Oct 25.

Central Scientific Instruments Organisation, Sector 30 C, Chandigarh 160030, India. Electronic address:

Airborne pathogens are small microbes that can cause a multitude of diseases (e.g., the common cold, flu, asthma, anthrax, tuberculosis, botulism, and pneumonia). As pathogens are transmitted from infected hosts via a number of routes (e.g., aerosolization, sneezing, and coughing), there is a great demand to accurately monitor their presence and behavior. Despite such need, conventional detection methods (e.g., colony counting, immunoassays, and various molecular techniques) generally suffer from a number of demerits (e.g., complex, time-consuming, and labor-intensive nature). To help overcome such limitations, nanomaterial-based biosensors have evolved as alternative candidates to realize portable, rapid, facile, and direct on-site identification of target microbes. In this review, nano-biosensors developed for the detection of airborne pathogens are listed and discussed in reference to conventional options. The prospects for the development of advanced nano-biosensors with enhanced accuracy and portability are also discussed.
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http://dx.doi.org/10.1016/j.envint.2020.106183DOI Listing
January 2021

Lignin-Bimetallic Nanoconjugate Doped pH-Responsive Hydrogels for Laser-Assisted Antimicrobial Photodynamic Therapy.

Biomacromolecules 2020 08 23;21(8):3216-3230. Epub 2020 Jul 23.

Center of Innovative and Applied Bioprocessing (CIAB), Department of Biotechnology (DBT), Government of India, Sector 81 (Knowledge City), S.A.S. Nagar 140306, Punjab, India.

Bioinspired nano-antimicrobials stand out in terms of cost effectiveness and scalability when compared to their chemically synthesized counterparts. There is limited efficacy of current antibiotics due to their interference with the immune system as well as development of antibiotic resistance. Lignin, which is a naturally abundant polyphenol-rich biopolymer, can be utilized for the fabrication of sustainable antimicrobial materials. In the present work, development of stable nanocomposite hydrogels embedded with lignin-based photodynamic nanoconjugates has been described. This could lead to complete eradication of microbial infection upon laser exposure. For designing such hydrogels, initially photosensitizer decorated lignin-metallic and lignin-bimetallic nanoconjugates were developed utilizing simple and nontoxic methods. These photodynamic nanoconjugates were then characterized and doped into a poly(acrylic acid)-based hydrogel in order to achieve efficient pH-triggered controlled release. The nanocomposite hydrogels allowed maximum transmission of light, promoting their applicability in antimicrobial photodynamic therapy. Utilization of hydrogel helped in better retention of nanoconjugates, maintaining their antimicrobial photodynamic efficacy as validated via IC measurement and live-dead cell imaging. The biocompatible pH-responsive photodynamic antimicrobial hydrogels developed herein could be potentially applicable in controlled drug delivery through the construction of wound dressings, as well as for developing antifungal, antibacterial, or antiviral nanocoatings.
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http://dx.doi.org/10.1021/acs.biomac.0c00695DOI Listing
August 2020

Development of agri-biomass based lignin derived zinc oxide nanocomposites as promising UV protectant-cum-antimicrobial agents.

J Mater Chem B 2020 01 4;8(2):260-269. Epub 2019 Dec 4.

Department of Nanomaterials and Application Technology, Center of Innovative and Applied Bioprocessing (CIAB), Sector 81 (Knowledge City), S.A.S. Nagar, 140306, Punjab, India.

Agri-biomass derived lignin is one of the most abundant natural nontoxic organic polymers. However, a major portion of lignin is underutilized, which is being left in the fields or thrown into rivers, causing waste accumulation. Utilization of the low-cost biomass-derived lignin serves a dual purpose by reducing agri-waste and by converting it into value-added materials. Here we describe the valorization of agri-biomass based lignin via its direct utilization in the green and one-step synthesis of zinc oxide nanocomposites. Lignin offered an easy and sustainable synthesis of nanocomposites in a water-ethanol mixture without the need to use any toxic material. The lignin derived nanomaterials showed excellent potential as antioxidant, UV-blocking and antimicrobial agents due to the synergistic effect of lignin and zinc oxide. Further, these nanocomposites were incorporated as an additive into a commonly used body cream to impart UV-blocking and antimicrobial properties. This one-step, cost-effective and green synthesis technique of lignin derived zinc oxide nanocomposites not only contributes to agro-waste reduction, but at the same time helps in the production of value-added materials.
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http://dx.doi.org/10.1039/c9tb01569hDOI Listing
January 2020

Engineering Lignin Stabilized Bimetallic Nanocomplexes: Structure, Mechanistic Elucidation, Antioxidant, and Antimicrobial Potential.

ACS Biomater Sci Eng 2019 Jul 19;5(7):3212-3227. Epub 2019 Jun 19.

Department of Nanomaterials and Application Technology, Center of Innovative and Applied Bioprocessing (CIAB), Sector 81 (Knowledge City), S.A.S. Nagar, Punjab 140306, India.

Lignin, being a natural antioxidant and antimicrobial underutilized biopolymer derived mainly from agro-waste, is a material of great interest. In this study, lignin was chosen as a matrix to synthesize silver-gold bimetallic and monometallic nanocomplexes to explore the synergistic antioxidant and antimicrobial properties of the lignin stabilized nanoagents. The synthesis of the nanocomplexes was carried out using a one pot method, utilizing lignin as the sole source for reducing, capping, and stabilizing the nanoagents. Further, characterization studies were performed to determine the exact structure of the nanocomplexes. The developed nanocomplexes were found to possess substantial phenolic and flavonoid contents, which contributed to their high antioxidant activity. Further, the antioxidant and antimicrobial activity of the lignin-bimetallic and monometallic nanocomplexes was evaluated and compared with pristine lignin. Moreover, the mechanism behind the antimicrobial activity of the nanocomplexes was elucidated through various methods, namely, reactive oxygen generation, nucleic acid leakage, and DNA cleavage studies. The obtained results were greatly supported by scanning electron microscopy, transmission electron microscopy, and live-dead cell imaging techniques. This study is a contribution in converting waste to value added functional nanomaterials for potential antioxidant and antimicrobial applications.
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http://dx.doi.org/10.1021/acsbiomaterials.9b00233DOI Listing
July 2019

Development of Gelatin Nanoparticle-Based Biodegradable Phototheranostic Agents: Advanced System to Treat Infectious Diseases.

ACS Biomater Sci Eng 2018 Feb 23;4(2):473-482. Epub 2018 Jan 23.

Department of Biotechnology Department of Pharmaceutical Technology (Biotechnology), and Department of Pharmaceutical Technology (Process Chemistry), National Institute of Pharmaceutical Education and Research (NIPER), Sector-67, S.A.S. Nagar 160062, Punjab, India.

Rose bengal (RB)-conjugated and -entrapped gelatin nanoparticle (GNP)-based biodegradable nanophototheranostic (Bd-NPT) agents have been developed for the efficient antimicrobial photodynamic therapy. The study reveals that the use of gelatin nanoparticles could bypass the chemicals such as potassium iodide, EDTA, calcium chloride and polymyxin nonapeptide for the penetration of drug into the cell membrane to achieve antimicrobial activity. We demonstrated that the singlet oxygen generated by the biodegradable gelatin nanoparticles (BdGNPs) could damage the microbial cell membrane and the cell dies. The key features of the successive development of this work include the environmentally benign amidation of RB with GNPs, which was so far unexplored, and the entrapment of RB into the gelatin nanoparticles (GNP). The RB-GNP exhibited potent and broad-spectrum antimicrobial activity and could be useful in treating multi-drug-resistant microbial infections.
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http://dx.doi.org/10.1021/acsbiomaterials.7b00751DOI Listing
February 2018

Development of nanobiocatalysts through the immobilization of Pseudomonas fluorescens lipase for applications in efficient kinetic resolution of racemic compounds.

Bioresour Technol 2017 Sep 11;239:464-471. Epub 2017 May 11.

Department of Pharmaceutical Technology (Biotechnology), National Institute of Pharmaceutical Education and Research, Sector 67, S.A.S. Nagar, 160062 Punjab, India. Electronic address:

The present work reports covalent immobilization of Pseudomonas fluorescens lipase (PFL) on functionalized multiwalled carbon nanotubes (MWCNTs) as a nanobiocatalyst (NBC). This nanobiocatalyst facilitates efficient kinetic resolution of (RS)-1-phenylethanol into (S)-1-phenylethanol [C=49.7%, ee=99.5%, ee=98.1% and E value=191.4]. The immobilized preparation (MWCNTs-PFL) showed ten-fold increase in activity, thermal stability upto 80 °C and recyclability (8 cycles). MWCNTs-PFL nanobioconjugate demonstrated better stability and enhanced activity compared to covalently immobilized PFL on other matrices (silver nanoparticles, gold nanoparticles and chitosan beads) used for the study. A statistical design [response surface methodology (RSM)] employed for the optimization of enzyme immobilization parameters made this study statistically more significant. Overall, the newly developed nanobiocatalyst has applications towards the kinetic resolution of racemic compounds.
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http://dx.doi.org/10.1016/j.biortech.2017.05.050DOI Listing
September 2017

Chemoenzymatic Route for the Synthesis of (S)-Moprolol, a Potential β-Blocker.

Chirality 2016 Apr 28;28(4):313-8. Epub 2016 Jan 28.

Department of Pharmaceutical Technology, National Institute of Pharmaceutical Education and Research, Nagar, Punjab, India.

A biocatalytic route for the synthesis of a potential β-blocker, (S)-moprolol is reported here. Enantiopure synthesis of moprolol is mainly dependent on the chiral intermediate, 3-(2-methoxyphenoxy)-propane-1,2-diol. Various commercial lipases were screened for the enantioselective resolution of (RS)-3-(2-methoxyphenoxy)propane-1,2-diol to produce the desired enantiomer. Among them, Aspergillus niger lipase (ANL) was selected on the basis of both stereo- and regioselectivity. The optimized values of various reaction parameters were determined such as enzyme (15 mg/mL), substrate concentration (10 mM), organic solvent (toluene), reaction temperature (30 °C), and time (18 h).The optimized conditions led to achieving >49% yield with high enantiomeric excess of (S)-3-(2-methoxyphenoxy)propane-1,2-diol. The lipase-mediated catalysis showed regioselective acylation with dual stereoselectivity. Further, the enantiopure intermediate was used for the synthesis of (S)-moprolol, which afforded the desired β-blocker.
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http://dx.doi.org/10.1002/chir.22574DOI Listing
April 2016

Bioinspired Nanotheranostic Agents: Synthesis, Surface Functionalization, and Antioxidant Potential.

ACS Biomater Sci Eng 2015 Jun 19;1(6):382-392. Epub 2015 May 19.

Department of Pharmaceutical Technology (Biotechnology), National Institute of Pharmaceutical Education and Research (NIPER), Sector-67, S.A.S. Nagar 160062, Punjab, India.

Bioinspired synthesis of nanomaterials is highly advantageous as a natural and cost-effective resource. Development of noble metal nanotheranostic agents was achieved through bioinspired synthetic routes. These biosynthesized nanoparticles were characterized by various analytical techniques including absorption spectroscopy, FTIR and electron microscopy (SEM and TEM). A large number of medicinal plants were screened, among which (PF, vajradanti) and (CS, green tea) were found to produce nanomaterials with higher yields. Plant (PF and CS) mediated metallic nanoparticles had added advantage of metal reduction and simultaneous phytochemical capping over chemically synthesized procedures, which require multiple reagents. Antioxidant potential of the nanomaterials was determined by in vitro antioxidant assays confirming substantial antioxidant properties, which was due to the presence of phytochemicals on the nanoparticle surface. Flavonoids and catechins on the nanomaterial surface served as the supplier of hydroxyl groups for further derivatization. The surface of the nanoparticles was engineered by conjugating imaging and therapeutic moieties, resulting in the formation of theranostic nanoagents. The multimodal agents were characterized and the extent of drug loading was determined to validate the efficacy of those nanoconjugates. These bioinspired multimodal nanoprobes can serve as essential diagnostic and therapeutic tools in ongoing biomedical research.
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http://dx.doi.org/10.1021/ab500171aDOI Listing
June 2015

Biocatalytic Approach for the Synthesis of Enantiopure Acebutolol as a β₁-Selective Blocker.

Chirality 2015 Jun 15;27(6):382-91. Epub 2015 May 15.

Department of Pharmaceutical Technology (Biotechnology), National Institute of Pharmaceutical Education and Research (NIPER), Punjab, India.

A new chemoenzymatic route is reported to synthesize acebutolol, a selective β1 adrenergic receptor blocking agent in enantiopure (R and S) forms. The enzymatic kinetic resolution strategy was used to synthesize enantiopure intermediates (R)- and (S)-N-(3-acetyl-4-(3-chloro-2-hydroxypropoxy)phenyl)butyramide from the corresponding racemic alcohols. The results showed that out of eleven commercially available lipase preparations, two enzyme preparations (Lipase A, Candida antarctica, CLEA [CAL CLEA] and Candida rugosa lipase, 62316 [CRL 62316]) act in enantioselective manner. Under optimized conditions the enantiomeric excess of both (R)- and (S)-N-(3-acetyl-4-(3-chloro-2-hydroxypropoxy)phenyl)butyramide were 99.9 and 96.8%, respectively. N-alkylation of both the (R) and (S) intermediates with isopropylamine gave enantiomerically pure (R and S)- acebutolol with a yield 68 and 72%, respectively. This study suggests a high yielding, easy and environmentally green approach to synthesize enantiopure acebutolol.
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http://dx.doi.org/10.1002/chir.22444DOI Listing
June 2015

Quantum dot/antibody conjugates for in vivo cytometric imaging in mice.

Proc Natl Acad Sci U S A 2015 Feb 20;112(5):1350-5. Epub 2015 Jan 20.

Edwin L. Steele Laboratory, Massachusetts General Hospital and Harvard Medical School, Boston, MA 02114.

Multiplexed, phenotypic, intravital cytometric imaging requires novel fluorophore conjugates that have an appropriate size for long circulation and diffusion and show virtually no nonspecific binding to cells/serum while binding to cells of interest with high specificity. In addition, these conjugates must be stable and maintain a high quantum yield in the in vivo environments. Here, we show that this can be achieved using compact (∼15 nm in hydrodynamic diameter) and biocompatible quantum dot (QD) -Ab conjugates. We developed these conjugates by coupling whole mAbs to QDs coated with norbornene-displaying polyimidazole ligands using tetrazine-norbornene cycloaddition. Our QD immunoconstructs were used for in vivo single-cell labeling in bone marrow. The intravital imaging studies using a chronic calvarial bone window showed that our QD-Ab conjugates diffuse into the entire bone marrow and efficiently label single cells belonging to rare populations of hematopoietic stem and progenitor cells (Sca1(+)c-Kit(+) cells). This in vivo cytometric technique may be useful in a wide range of structural and functional imaging to study the interactions between cells and between a cell and its environment in intact and diseased tissues.
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http://dx.doi.org/10.1073/pnas.1421632111DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4321304PMC
February 2015

Biosynthesis of silver nanoparticles: Elucidation of prospective mechanism and therapeutic potential.

J Colloid Interface Sci 2014 Feb 22;415:39-47. Epub 2013 Oct 22.

Department of Pharmaceutical Technology (Biotechnology), National Institute of Pharmaceutical Education and Research, Sector-67, S.A.S. Nagar 160062, Punjab, India.

The synthesis of silver nanoparticles (AgNPs) was accomplished using Syzygium cumini fruit extract at room temperature. Various techniques were used to characterize the newly synthesized silver nanoparticles and their size was determined to be 10-15nm. Important findings of this study were the identification of biomolecules responsible for the synthesis of silver nanoparticles and elucidate the mechanism of biosynthesis. Flavonoids present in S. cumini were mainly responsible for the reduction and the stabilization of nanoparticles. The antioxidant properties of AgNPs were evaluated using various assays. The nanoparticles were also found to destroy Dalton lymphoma cell lines under in vitro condition. Silver nanoparticles (100μg/mL) decreased the viability of Dalton lymphoma (DL) cell lines up to 50%. The studies describing the biosynthesis of silver nanoparticles by fruit extract followed by the investigation of synthesis mechanism and anti-cancer activities may be useful for nanobiotechnology research opening a new arena in this field.
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http://dx.doi.org/10.1016/j.jcis.2013.10.018DOI Listing
February 2014

Targeted nanoagents for the detection of cancers.

Mol Oncol 2010 Dec 8;4(6):511-28. Epub 2010 Sep 8.

Center for Systems Biology, Harvard Medical School and Massachusetts General Hospital, Boston, MA 02114, USA.

Nanotechnology has enabled a renaissance in the diagnosis of cancers. This is due, in part to the ability to develop agents bearing multiple functionalities, including those utilized for targeting, imaging, and therapy, allowing for the tailoring of the properties of the nanomaterials. Whereas many nanomaterials exhibit localization to diseased tissues via intrinsic targeting, the addition of targeting ligands, such as antibodies, peptides, aptamers, and small molecules, facilitates far more sensitive cancer detection. As such, this review focuses upon some of the most poignant examples of the utility of affinity ligand targeted nanoagents in the detection of cancer.
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http://dx.doi.org/10.1016/j.molonc.2010.08.003DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2981649PMC
December 2010

High-yielding syntheses of hydrophilic conjugatable chlorins and bacteriochlorins.

Org Biomol Chem 2009 Sep 2;7(17):3430-6. Epub 2009 Jul 2.

Center for Molecular Imaging Research, Harvard Medical School and Massachusetts General Hospital, 149 13th St., Rm 5406, Charlestown, MA 02129, USA.

Next-generation photodynamic therapy agents based upon the conjugation of multiple photosensitizers to a targeting backbone will allow for more efficacious light-based therapies. To this end, we have developed glucose-modified chlorins and bacteriochlorins featuring a reactive carboxylic acid linker for conjugation to targeting moieties. The photosensitizers were synthesized in relatively high yields from meso-tetra(p-aminophenyl)porphyrin, and resulted in neutral, hydrophilic chromophores with superb absorption profiles in the far-red and near-infrared portions of the electromagnetic spectrum. In addition, conjugation of these photosensitizers to a model nanoscaffold (crosslinked dextran-coated nanoparticles) demonstrated that the inclusion of hydrophilic sugar moieties increased the number of dyes that can be loaded while maintaining suspension stability. The described compounds are expected to be particularly useful in the synthesis of a number of targeted nanotherapeutic systems.
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http://dx.doi.org/10.1039/b908713cDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2749955PMC
September 2009

Synthesis and photophysical properties of sulfonamidophenyl porphyrins as models for activatable photosensitizers.

J Org Chem 2009 Aug;74(16):5894-901

Center for Systems Biology, Massachusetts General Hospital and Harvard Medical School, 149 13th Street, Room 5406, Charlestown, Massachusetts 02129, USA.

The ability to localize agents to specific anatomic sites remains an important aspect in designing more efficient therapeutics. Light-activated therapies, in particular, allow for the focal ablation of target tissues and cells. In order to increase the specificity of these agents, stimuli-activated systems have been developed, which are nonphototoxic in the absence of activation. To this end, we propose a novel paradigm for excited state quenching and activation based upon the direct conjugation of quenching moieties to the porphyrinic macrocycle. Model compounds, based upon meso-(p-aminophenyl)porphyrins were synthesized bearing 1 to 4 sulfonamide-linked 2,4-dinitrobenzene. The singlet oxygen and fluorescence quantum yields of these compounds were obtained and compared, as well as the kinetics of activation with relevant activating agents. In addition, methods were developed to further modify the porphyrin in order to modulate the polarity and effect conjugation to biomolecules or nanoparticulate scaffolds. These systems may prove useful in the treatment of a number of disease states, such as cancer and bacterial infection.
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http://dx.doi.org/10.1021/jo900832yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2888918PMC
August 2009

Imidazole metalloporphyrins as photosensitizers for photodynamic therapy: role of molecular charge, central metal and hydroxyl radical production.

Cancer Lett 2009 Sep 5;282(1):63-76. Epub 2009 Apr 5.

Wellman Center for Photomedicine, Massachusetts General Hospital, Boston, MA, USA.

The in vitro photodynamic therapy activity of four imidazole-substituted metalloporphyrins has been studied using human (HeLa) and mouse (CT26) cancer cell lines: an anionic Zn porphyrin and a homologous series of three cationic Zn, Pd or InCl porphyrins. A dramatic difference in phototoxicity was found: Pd cationic>InCl cationic>Zn cationic>Zn anionic. HeLa cells were more susceptible than CT26 cells. Induction of apoptosis was demonstrated using a fluorescent caspase assay. The anionic Zn porphyrin localized in lysosomes while the cationic Zn porphyrin localized in lysosomes and mitochondria, as assessed by fluorescence microscopy. Studies using fluorescent probes suggested that the cationic Pd porphyrin produced more hydroxyl radicals as the reactive oxygen species. Thus, the cationic Pd porphyrin has high potential as a photosensitizer and gives insights into characteristics for improved molecular designs.
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http://dx.doi.org/10.1016/j.canlet.2009.02.054DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2782654PMC
September 2009

Synthesis of porphyrins bearing 1-4 hydroxymethyl groups and other one-carbon oxygenic substituents in distinct patterns.

Tetrahedron 2007 Oct;63(43):10657-10670

Department of Chemistry, North Carolina State University, Raleigh, NC 27695-8204, USA.

Porphyrins that bear one-carbon oxygenic substituents (hydroxymethyl, formyl, ester) directly attached to the macrocycle afford a compact architecture that is attractive for diverse applications. Routes to 9 porphyrins bearing such groups in distinct architectures (A(4)-, trans-A(2)-, trans-A(2)B(2)-, trans-AB- and trans-AB(2)C-porphyrins) have been explored (A = hydroxymethyl), including porphyrins bearing two one-carbon units in different oxidation states (hydroxymethyl/ester, formyl/ester). The hydroxymethyl group was introduced via TBDMS-protected dipyrromethane precursors.
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http://dx.doi.org/10.1016/j.tet.2007.07.108DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2084395PMC
October 2007

Rational routes to formyl-substituted chlorins.

J Org Chem 2007 Jul 22;72(15):5839-42. Epub 2007 Jun 22.

Department of Chemistry, North Carolina State University, Raleigh, NC 27695-8204, USA.

Two distinct approaches have been developed for the synthesis of chlorins bearing formyl groups: (1) reaction of an acetal-substituted 1-acyldipyrromethane with 2,3,5,6-tetrahydro-1,3,3-trimethyldipyrrin to give upon hydrolysis a 5-formylchlorin and (2) Pd-mediated coupling of a bromochlorin with a one-carbon synthon (hydroxymethyl tributyltin or CO) to give a 13-, 15-, or 3,13-formylchlorin. The zinc chlorins exhibit long-wavelength peak absorption maxima ranging from 626 to 667 nm, indicating the wavelength tunability afforded by formyl substitution.
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http://dx.doi.org/10.1021/jo0707885DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2525510PMC
July 2007

Masked imidazolyl-dipyrromethanes in the synthesis of imidazole-substituted porphyrins.

J Org Chem 2006 Nov;71(23):8807-17

Department of Chemistry, North Carolina State University, Raleigh, North Carolina 27695-8204, USA.

Imidazole-substituted metalloporphyrins are valuable for studies of self-assembly and for applications where water solubility is required. Rational syntheses of porphyrins bearing one or two imidazol-2-yl or imidazol-4-yl groups at the meso positions have been developed. The syntheses employ dipyrromethanes, 1-acyldipyrromethanes, and 1,9-diacyldipyrromethanes bearing an imidazole group at the 5-position. The polar, reactive imidazole unit was successfully masked by use of (1) the 2-(trimethylsilyl)ethoxymethyl (SEM) group at the imidazole pyrrolic nitrogen, and (2) a dialkylboron motif bound to the pyrrole of the dipyrromethane and coordinated to the imidazole imino nitrogen. The nonpolar nature of such doubly masked imidazolyl-dipyrromethanes facilitated handling. Selected masked dipyrromethanes were characterized by 11B and 15N NMR spectroscopy. Five distinct methods were examined to obtain trans-A2B2-, trans-AB2C-, and trans-AB-porphyrins. Each porphyrin contained one or two SEM-protected imidazole units. The SEM group could be removed with TBAF or HCl. Two zinc(II) porphyrins and a palladium(II) porphyrin bearing a single imidazole moiety were prepared and subjected to alkylation (with ethyl iodide, 1,3-propane sultone, or 1,4-butane sultone) to give water-soluble imidazolium- porphyrins. This work establishes the foundation for the rational synthesis of a variety of porphyrins containing imidazole units.
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http://dx.doi.org/10.1021/jo061461rDOI Listing
November 2006

Refined Synthesis of 2,3,4,5-Tetrahydro-1,3,3-trimethyldipyrrin, a Deceptively Simple Precursor to Hydroporphyrins.

Org Process Res Dev 2005 ;9(5):651-659

Department of Chemistry, North Carolina State University, Raleigh, North Carolina 27695-8204, USA. Email:

2,3,4,5-Tetrahydro-1,3,3-trimethyldipyrrin (1) is a crucial building block in the rational synthesis of chlorins and oxochlorins. The prior 5-step synthesis of 1 from pyrrole-2-carboxaldehyde (2) employed relatively simple and well-known reactions yet suffered from several drawbacks, including limited scale (>/= 0.5 g of 1 per run). A streamlined preparation of 1 has been developed that entails four steps: (i) nitro-aldol condensation of 2 and nitromethane under neat conditions to give 2-(2-nitrovinyl)pyrrole (3), (ii) reduction of 3 with NaBH(4) to give 2-(2-nitroethyl)pyrrole (4), (iii) Michael addition of 4 with mesityl oxide under neat conditions or at high concentration to give gamma-nitrohexanonepyrrole 5, and (iv) reductive cyclization of 5 with zinc/ammonium formate to give 1. Several multistep transformations have been established, including the direct conversion of 2 --> 1. The advantages of the new procedures include (1) fewer steps, (2) avoidance of several problematic reagents, (3) diminished consumption of solvents and reagents, (4) lessened reliance on chromatography, and (5) scalability. The new procedures facilitate the preparation of 1 at the multigram scale.
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http://dx.doi.org/10.1021/op050087eDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2614668PMC
January 2005