Skip to main content
NCBI home page
ACS Medicinal Chemistry Letters logoLink to ACS Medicinal Chemistry Letters
. 2026 Jul 31;17(8):1780–1786. doi: 10.1021/acsmedchemlett.6c00168

Understanding the Photodynamic Behavior of Red Emitting Re(I)dipyrrinates in Triple-Negative Breast Cancer Cells

Neha Manav a,b, Jaydeepsinh Chavda a, Dhiraj Bhatia c, Iti Gupta a,*
PMCID: PMC13488103  PMID: 42622023

Abstract

The Re­(I)­dipyrrinates complexes having oligo ethylene glycol (OEG) and thioglucose/thiogalactose sugars at the C-8 position are explored for anticancer applications. The X-ray crystal structure of Re­(I)­dipyrrinate having a thiogalactose sugar revealed distorted octrahedral geometry of the central metal. The Re­(I)­dipyrrinates showed red emission (600–900 nm) with noticeably large Stokes shifts (∼5890–6800 cm–1), a highly desirable property for bioimaging application. The Re­(I)­dipyrrinates were found to be nontoxic in dark conditions on triple negative breast cancer cells (TNBC), whereas Re­(I)­dipyrrinate with OEG group and thioglucose sugar displayed excellent phototoxicity in TNBC with IC50 values of 2.6 and 1.5 μM, respectively. The Re­(I)­dipyrrinate with OEG group displayed preferential colocalization in the lipid droplets and caused lipid peroxidation after light exposure. Additionally, all Re­(I)­dipyrrinates were nontoxic to the normal retinal pigment epithelial cells (RPE-1) both in the dark and under light irradiation, reflecting suitable behavior as the anticancer agents for photodynamic therapy.

Keywords: Triple negative breast cancer, photodynamic therapy, Re complex, red emission, ER-stress

graphic file with name ml6c00168_0011.webp

graphic file with name ml6c00168_0010.webp

Rhenium complexes have been notably explored in the literature, mainly for their applications in catalysis, in OLEDs, and in therapies owing to their high ISC. Rhenium complexes have always been a fascinating area of research in therapy, due to the diagnostic and therapeutic applicability of their radioisotopes (186Re, 188Re, and 99mTc), which can bind within the same ligand framework and emit γ radiation. − Among potential ligands, dipyrromethene (dipyrrin) scaffolds are favorable chelators for metal complexation that offer both stability and tunability by varying meso-substituents. −

Of particular interest is the meso-pentafluorophenyl group, an electron-withdrawing moiety on dipyrrin which provides the stabilization to the dipyrrin scaffold and makes the scaffold prone to Nu-substitution at para-fluorine site with thiols amines and alcohols. ,, Such substitutions are known to improve their polar media solubility, particularly tailored for biomedical applications. Moreover, the fluorine group modulates pharmacokinetics by increasing the transport rate across a lipid membrane, which promotes selective accumulation in malignant cells. They also enhance lipophilicity, singlet oxygen generation, and more importantly photostability, making them attractive for PDT. Due to their size similarity with hydrogen, F atom mimics parent molecules in the biochemical process while imparting distinct physical and chemical properties. , Furthermore, fluorinated analogs like benzochlorin have displayed higher tumor uptake and selectivity than their nonfluorinated versions, as reported by Li and co-workers. Similarly, rhenium–phenanthroline complexes having oligo-ethylene chains also aid in enhanced absorption in HeLa cells, as explored by Massi and group. For optimal biological performance, it is imperative to maintain balance between hydrophobic and hydrophilic properties. Some moieties such as oligoethylene carbohydrates, lipids, and proteins generally facilitate the cell uptake. , In particular, carbohydrate linked moieties enhance the active drugs uptake by cell and bacteria. The carbohydrate–cisplatin conjugate , have demonstrated better selectivity and effectiveness in cancer cells than cisplatin alone. It is mainly because of high metabolic activity and thus increased glucose transporters (GLUTs) expression in cancerous cells leading to higher uptake of sugar moiety. Expanding on this strategy, thio-carbohydrates, used as nucleophiles to achieve glycosylation, are more stable than oxy-carbohydrates due to Sulfur’s low affinity for protons in hydrolysis and provide stability over acid hydrolysis. Similarly, it inhibits the glycosidase reaction where the enzyme can easily cleave oxy-carbohydrates bond but remain ineffective in cleaving the bond between thio-carbohydrates.

In this work, we have developed thioglycosylated and oligoethylene glycol (OEG)-linked Re­(I)­dipyrrinates. The photophysical properties of these Re­(I)­dipyrrinates were explored in different solvents. The idea was to enhance cell uptake in cancerous cells, improving the activity of photosensitizers for PDT. The thio-acetyl glycosylated Re­(I)­dipyrrinates (Re1 and Re2) were synthesised from Re­(I)­dipyrrinate (1) and made them water soluble by base treatment. − The reaction of dipyrrin 2 with Re­(CO)5Cl led to the formation of Re­(I)­dipyrrinate Re3. (Scheme ).

1.

1

Open in a new tab

a Reagents and conditions: (a) dry diethylamine (DEA), dry DMF, rt, 12 h, Ac-GAL/Ac-GLU; (b) NaOMe, rt, 24 h, 40 °C; (c) Re­(CO)5Cl, dry toluene, dry TEA, PPh3, reflux 3 h.

All starting materials and targeted Re­(I)­dipyrrinates Re1, Re2, and Re3 were well characterized by spectroscopic techniques like MALDI mass spectrometry (MALDI-TOF), IR, and 1H and 13C NMR spectroscopies. The IR spectra of Re1 and Re2 show the vibrational bands corresponding to their Re­(I)­dipyrrinate (1) before glycosylation which is like their respective dipyrrin except for the vibrations for thio-acetyl glycosylated moiety. For Re­(I) dipyrrinate the CO stretching frequency of the -OAc group lies at ∼1745 cm–1 and the C–O–C asymmetric stretching vibration is found at ∼1217–1224 cm–1. The C–H bending vibration of CH3 was observed at ∼1380 cm–1, and the C–H stretching vibration is at ∼2920 cm–1. In the cases of Re1 and Re2, the three C–O units having fac isomer arrangement, the carbonyl groups showed the typical pattern for the C–O stretching vibrations (asymmetric and symmetric). Generally, CO stretching vibrations are very delicate to the electronic environment. For rhenium dipyrrinate Re1 the vibrations have been witnessed at around 2017, 1925, 1884 cm–1; i.e., C–O stretching vibrations and similar vibration modes were also observed for Re2 and Re3. These similar IR values of the CO group around the rhenium metal center in all three compounds indicated a similar electronic environment.

The 1H NMR spectra of all-metal dipyrrinates were recorded in CDCl3. The partial 1H NMR and homo-COSY spectra of Re2 complex are shown in Figure . The α-pyrrolic protons (a/a′) of Re­(I)­dipyrrinate Ac-Re2 showed up at ∼7.48 ppm, and β-pyrrolic protons were found at 6.44 (c/c′) and 6.20 ppm (b/b′). The aliphatic protons of glucose conjugate occur below 5.30 ppm (Figure ). In general, for all reported metal dipyrrinates, the aliphatic protons for glycosylated moiety and oligoethylene moiety are observed below 5.5 ppm and the β-pyrrolic protons for all metal dipyrrinates observed between 6.0 and 6.2 ppm and α-pyrrolic protons ∼7.4-7.5 ppm accompanied by other aromatic protons between 7.0 and 7.5 ppm. In 19F NMR, peaks were found to be two doublets which further split into doublets due to the different magnetic and chemical environments of five F atoms and observed around −131, −132, −138, −139 ppm corresponding to 4-F atoms. This indicates the F atom of pentafluorophenyl ring has been selectively substituted by a thio-glycosyl group. The 19F NMR signals of Re1 and Re2 were found to be influenced by the different substituent around the metal center, as the environment is not symmetric; hence all F atoms (-ortho, -meta) present on meso-position of dipyrrin ring were found to face the different chemical environment which can be seen as four different signals for individual F atoms. Both water-soluble complexes (WSRe1 and WSRe2) were characterized by ESI-HRMS (Figures S23 and S25) and their HPLC purities (Figures S24 and S26) also tested.

1.

1

Open in a new tab

Partial 1H NMR and 1H–1H COSY spectra of Re2 in CDCl3.

The single crystals of Re­(I)­dipyrrinate Re2 were grown by slow evaporation of n-pentane/CHCl3 solution over 2–3 weeks. The plate-shaped crystal in the monoclinic form was obtained for Re­(I)­dipyrrinate Re2 in red color with the P21/c (No. 14) space group. Before single-crystal analysis, the measured crystal size was 0.16 mm × 0.29 mm × 0.73 mm.

The X-ray crystal structure of Re­(I)­dipyrrinate Re2 (CCDC 2022651) is shown in Figure and its crystallographic parameters were arranged in Table ST1 in Supporting Inforamtion. From the crystal, it was observed that the Re­(I) center along with two carbonyl ligands is in the plane of the dipyrrin core; however the third carbonyl and triphenylphosphine, trans position, spread out in a different direction which is vertically aligned to plane of dipyrrin. Selected bond distances, dihedral angles, and bond distances of Re2 are shown in Table ST2 in Supporting Information. The observed dihedral angles between the plane of dipyrrin and attached meso-substituent [C4–C5–C31–C36 and C6–C5–C31–C32] are 77.52(1)° and 78.72(1)°. The dihedral angle of Re2 was found to be 12° higher than that of Re­(I)­dipyrrinate (1). The complex Re2 has distorted octahedral geometry and remains as C s symmetry as previously reported Re­(I) dipyrrinates. The bond distances of Re–N1 and Re–N2 are 2.157(6) and 2.142(7) Å which are comparable to Re­(I)­dipyrrinate (1) at 2.168(18) and 2.172(15) Å, respectively. The observed bond angle between N1–Re–N2 for Re2 was 84.22(2)°. The distance between three carbonyls and rhenium center (Re–C­(O)) was also analogous with the previous report and observed between 1.907(8) and 1.932(9). Along with this, the observed Re–P length was 2.501(2) Å, which was marginally greater than reported in mixed ligand Re­(I)­dicarbonyl complexes (Table ST2 in Supporting Information).

2.

2

Open in a new tab

ORTEP diagram of rhenium dipyrrinate Re2, thermal ellipsoids are shown at the 50% probability level.

The UV–vis absorption studies of Re­(I)­dipyrrinates Re1, Re2, and Re3 were performed in a range of solvents including toluene, hexane, DMSO, and DMF. Representative UV–visible and emission spectra in toluene are shown in Figure a and Table ST3. The intense absorption band detected around 480–500 nm in toluene can be assigned to π → π* transitions and thus designated as a ligand centered transition as this transition is similar to the free ligand dipyrrin and also similar to already reported dipyrrin complex. ,− Subsequent extinction coefficients (ε) of the major absorption bands occurred from 20 000 to 26 300 M–1 cm–1 in toluene (Table ST3). Apart from this, toward the lower energy side, i.e., around wavelength 320 nm due to high energy intra-ligand transition. The hump at ∼440 nm is attributed to S0 → S2 transitions , in Re­(I)­dipyrrinates (Re1, Re2, and Re3) which matches results of already reported Re­(I)­dipyrrinates. Absorption studies in different solvents such as DMF, hexane, DMSO, and CHCl3 are shown in Supporting Information (Figure S27).

3.

3

Open in a new tab

Photophysical studies of Re­(I)­dipyrrinates in toluene: (a) molar extinction coefficient (2.4 μM concentration); (b) normalized emission in toluene; λex = 485 nm; (c) photostability property of Re3 after light irradiation (Luzchem photoreactor, 400–700 nm, 24 J/cm2).

The emission range for Re­(I)­dipyrrinates observed in the NIR region was from ∼620 to 850 nm in toluene, DMF, DMSO, and hexane (Figure b and Figure S28), which was highly red-shifted. The emission maxima of Re­(I)­dipyrrinates were found to independent of solvent behavior and thus observed around the same maxima. However, a comparison of Re­(I)­dipyrrinates (Re1–Re3) confirmed that fluorophenyl carbohydrate derivatives (Re1, Re2) were retaining the emission maxima and pattern similar to their starting rhenium complex (1) and are ∼100 nm red shifted compared with Re3. The comparative emission studies of Re­(I)­dipyrrinates Re1–Re3 in deoxygenated and oxygenated solvents (DMSO, DMF, and hexane) were also performed and shown in Figure S29. For all three Re­(I)­dipyrrinates, a large Stokes shift of ∼5890–6800 cm–1 was detected in a range of solvents such as toluene, DMSO, DMF, and hexane (Table ST3) and the Stokes shift for Re2 in toluene solvent, which is around 6755 cm–1 (255 nm), is shown in Supporting Information (Figure S30). The high Stokes shift value is advantageous in overcoming the cellular autofluorescence, which arises from the fluorophores in cytoplasm or mitochondria of the cell after light excitation. The photostability study suggested that Re3 is quite photostable even after light irradiation for 90 min (Figure c). The singlet oxygen quantum yields of all Re­(I)­dipyrrinates (Re1–Re3) were recorded in phosphate buffer (PBS) using methylene blue (ϕΔ = 0.52 in water) as a standard. The result suggested that Re1 (ϕΔ = 0.88) showed excellent singlet oxygen quantum yield compared to Re3 (ϕΔ = 0.52) in PBS. The singlet oxygen plots of all complexes are shown in the Supporting Information (Figure S31).

The dynamic light scattering (DLS) study of Re3 was carried out, and the plots exhibited aggregation behavior even at low concentrations (50 nM) up to 96 h (Figure S32). The shake-flask method was used to determine the log P values of all the Re­(I)­dipyrrinates (Re1, Re2, Re3, WS-Re1, and WS-Re2). Their partition coefficients were evaluated in a 1:1 ratio in a mixture of 2-octanol and PBS. As expected, the water-soluble complexes were found to be more hydrophilic in nature than their acetylated counterparts, according to the obtained log P values. The lop P values of Re3 and WS-glycosylated Re complexes were found to be between 2.3 and 3.2 (Supporting Information, Table ST4). This experiment demonstrated good cell permeability of Re3 with an OEG chain and water-soluble glycosylated complexes for biological applications.

The photocytotoxicity studies of all Re­(I)­dipyrrinates were carried out on breast cancer cell line (MDA-MB-231 cells) and RPE-1 (human retinal pigment epithelial-1). Antitumor activity was assessed by MTT assays (Table ) in light and dark conditions on both the cells. Among all these Re­(I)­dipyrrinates, Re3 and WSRe1 showed excellent cell growth inhibition after light irradiation with IC50 values of 2.58 μM and 1.45 μM, respectively, against MDA-MB-231 cells. While in the absence of light both compounds showed minimal cytotoxicity with IC50 values of 33.02 μM and 24.44 μM, respectively. In a further check of the cytotoxicity of noncancerous cells (RPE-1), results suggested that all Re complexes were nontoxic to cells even after light irradiation (Table ). , Flow cytometry experiments were carried out to understand the cellular uptake of Re3 in MDA-MB-231 and RPE1 cells. Interestingly, flow cytometry data suggested that Re3 showed higher cellular uptake in TNBC cells (Figure S34 in Supporting Information) as compared to RPE1 cells. These results can be correlated with photocytotoxicity activity of Re3 in TNBC.

1. Anti-proliferative activity of rhenium­(I)­dipyrrinates.

  antiproliferative activity (μM)
  MDA-MB-231
 RPE-1
compd dark light PI dark light PI
Re1 40.9 ± 2.1 31.76 ± 2.2 1.28 >50 >50  
Re2 34.15 ± 1.0 32.00 ± 1.8 1.06 >50 >50  
Re3 33.02 ± 2.0 2.58 ± 3.1 12.79 28.45 ± 0.4215 19.24 ± 1.0019 1.47
WSRe1 24.44 ± 5.9752 1.45 ± 4.1165 16.85 >50 32.45 ± 2.6547 >1.54
WSRe2 13.68 ± 6.0029 10.66 ± 2.0490 1.28 >50 40.85 ± 1.2524 >1.22
Open in a new tab
a

PI: photocytotoxicity index.

The most potent Re­(I)­dipyrrinate (Re3) was selected for intracellular colocalization based on the outcomes of photocytotoxicity. Confocal microscopy was used to examine the colocalization of Re3 (20 μM) after it was incubated in MDA-MB-231 cells for 12 h at 37 °C (Figure ). The specific dyes for endoplasmic reticulum (ER) and lipid droplet (LDs) were incubated for 30 min for colocalization studies. The results indicated that compound Re3 demonstrated effective colocalization in ER and LDs (Figure ) with Pearson’s correlation coefficient (PCC) values of around 0.55 and 0.85, respectively.

4.

4

Open in a new tab

Subcellular colocalization of compound Re3 (20 μM), showing red emission in MDA-MB-231 cells after 12 h incubation with both trackers (10 μM). Scale bar: 10 μm.

The level of reactive oxygen species (ROS) generated upon light irradiation of the photosensitizer (PS) is the primary determinant of the therapeutic impact of PDT drugs. Using confocal microscopy, the dichlorofluorescein diacetate (DCFDA) test was used to investigate photosensitizer (Re3)-mediated ROS production in cancer cells (Figure ). By measuring the emission intensity of the oxidized product of DCFDA (DCF dye) at 525 nm, the amount of ROS produced in this experiment was determined. After being treated with MDA-MB-231 breast cancer cells, Re3 (20 μM) was left in the dark for 12 h. Two sets of plates were exposed to light (Luzchem photoreactor, 400–700 nm, 45 min) and darkness, respectively. Following this, DCFDA (10 μM) was added to each plate, and they were incubated for 30 min. Both the light and dark plates showed bright green fluorescence (Figure ); the intensity of the fluorescence was much greater in the light condition. The findings indicated that the molecule could generate ROS in cancer cells following light irradiation that triggered the death of cancer cells.

5.

5

Open in a new tab

Intracellular ROS detection DCF detection with and without Re3 (20 μM) in MDA-MB-231 cells in light and dark. Light source: 400–700 nm, 24 J/cm2, 45 min. Scale bar: 10 μm.

The type of intracellular ROS generation was detected by taking dihydrorhodamine 123 (DHR 123; superoxide sensor) and singlet oxygen sensor green (SOSG; probe for detecting singlet oxygen). Figure clearly depicted a rise in the intensity of green color with Re3 in TNBC cells, implying that Re3 could generate significant amount of superoxide (O2 •–) and singlet oxygen after incubation with DHR 123 and SOSG, respectively.

6.

6

Open in a new tab

Selective ROS detection by DHR123 and SOSG after Re3 (20 μM) in MDA-MB-231 cells. Light source: 400–700 nm, 24 J/cm2, 45 min. Scale bar: 10 μm.

To understand the mechanism of cell death by the Re3 complex, an immunofluorescence study (IHC) was carried out with glutathione peroxidase 4 (GPX4; lipid peroxidation biomarker) antibodies. It is observed that an expression of GPX4 enzyme is significantly higher in control cells as compared to the cells treated with Re3 complex. The diminution of green emission of the GPX4 biomarker in TNBC cells after treatment with the Re3 complex supported this observation (Figure ). GPX4 is an antioxidant enzyme that monitors and regulates the lipid peroxide levels. As per the literature, the elevation of lipid peroxides is intertwined with the inhibition of the GPX4 enzyme and the ferroptosis process. The subcellular colocalization studies of the Re3 complex were carried out in light (Figure ). At zero minute (under dark conditions), a higher amount of Re3 complex was accumulated in LDs (PCC = 0.78) compared to ER. After light irradiation (at 45 min), the LDs were ruptured noticeably, and compound localization was higher in ER (PCC = 0.78). The confocal images of Figures and suggested that the Re3 complex may be involved in ROS-mediated lipid peroxidation, which in turn leads to ferroptotic cell death.

7.

7

Open in a new tab

Effect of Re3 (20 μM) on GPX4 expression in MDA-MB-231 cells by immunocytochemistry. Scale bar: 10 μm.

8.

8

Open in a new tab

Effect of light (400–700 nm, 24 J/cm2) on cellular colocalization after Re3 (20 μM) in MDA-MB-231 cells at different time intervals. Scale bar: 10 μm.

In summary, three Re­(I) dipyrrinates were developed and examined for the anticancer applications using PDT. X-ray crystal analysis of Re­(I) dipyrrinate with thiogalactose unit showed distorted octahedral geometry of the central metal. Re­(I) dipyrrinates displayed bright red emission with large Stokes shifts (5890–6800 cm–1). All three complexes were nontoxic in dark conditions against TNBC cells. Re­(I) dipyrrinate with OEG and water-soluble thioglucose groups exhibited remarkable phototoxicities in TNBC cells with IC50 values of 2.6 and 1.5 μM, respectively. Confocal images revealed substantial colocalization of Re3 complex in LDs and caused ROS mediated lipid peroxidation. Furthermore, Re­(I) dipyrrinates were nontoxic to normal epithelial cells under light and dark conditions. In a nutshell, Re­(I) dipyrrinates have excellent potential to be explored as PDT agents for cancer diagnosis and treatment in the future.

Supplementary Material

ml6c00168_si_001.cif (4.1MB, cif)
ml6c00168_si_002.pdf (156.1KB, pdf)
ml6c00168_si_003.pdf (1.2MB, pdf)

Acknowledgments

I.G. is grateful to IIT Gandhinagar and ANRF for infrastructure and financial support. N.M. is thankful to ANRF, GoI, for NPDF Fellowship (PDF/2023/002568). J.C. is grateful to the Department of Science and Technology (DST), GoI, for INSPIRE Fellowship (IF190158). D.B. acknowledges ANRF, GoI for ARG funding.

Glossary

Abbreviations

OEG

oligoethylene glycol

TNBC

triple-negative breast cancer

PDT

photodynamic therapy

ER

endoplasmic reticulum

LDs

lipid droplets

PS

photosensitizer

ROS

reactive oxygen species.

The Supporting Information is available free of charge at https://pubs.acs.org/doi/10.1021/acsmedchemlett.6c00168.

  • Crystallographic information results (CIF)

  • checkCIF/PLATON report (PDF)

  • Synthetic procedure and characterization data including mass, 1H, 13C, 19F, 31P NMR, and HPLC purity of the reported compounds; photophysical studies (PDF)

N.M.: methodology, investigation, software, data curation, writingoriginal draft. J.C.: biological methods, investigation, software-visualization. D.B.: biological methods, writingreview and editing. I.G.: conceptualization, supervision, writingreview and editing, funding acquisition, project administration. The manuscript was written through contributions of all authors. All authors have given approval to the final version of the manuscript.

Financial support was received from ANRF, GoI (Grant No. ANRF/ARG/2025/004144/CS).

No unexpected or unusually high safety hazards were encountered. All confocal microscopy images (Figures –) were obtained with the standard default acquisition parameters.

The authors declare no competing financial interest.

References

  1. Talukdar K., Sinha Roy S., Amatya E., Sleeper E. A., Le Magueres P., Jurss J. W.. Enhanced Electrochemical CO2 Reduction by a Series of Molecular Rhenium Catalysts Decorated with Second-Sphere Hydrogen-Bond Donors. Inorg. Chem. 2020;59:6087–6099. doi: 10.1021/acs.inorgchem.0c00154. [DOI] [PubMed] [Google Scholar]
  2. Zhao G. W., Zhao J. H., Hu Y. X., Zhang D. Y., Li X.. Recent Advances of Neutral Rhenium­(I) Tricarbonyl Complexes for Application in Organic Light-Emitting Diodes. Synth. Met. 2016;212:131–141. doi: 10.1016/j.synthmet.2015.12.014. [DOI] [Google Scholar]
  3. Bauer E. B., Haase A. A., Reich R. M., Crans D. C., Kühn F. E.. Organometallic and Coordination Rhenium Compounds and Their Potential in Cancer Therapy. Coord. Chem. Rev. 2019;393:79–117. doi: 10.1016/j.ccr.2019.04.014. [DOI] [Google Scholar]
  4. Agorastos N., Borsig L., Renard A., Antoni P., Viola G., Spingler B., Kurz P., Alberto R.. Cell-Specific and Nuclear Targeting with [M­(CO)3]+ (M = 99mTc, Re)-Based Complexes Conjugated to Acridine Orange and Bombesin. Chem.Eur. J. 2007;13:3842–3852. doi: 10.1002/chem.200700031. [DOI] [PubMed] [Google Scholar]
  5. Knopf K. M., Murphy B. L., Macmillan S. N., Baskin J. M., Barr M. P., Boros E., Wilson J. J.. In Vitro Anticancer Activity and in Vivo Biodistribution of Rhenium­(I) Tricarbonyl Aqua Complexes. J. Am. Chem. Soc. 2017;139:14302–14314. doi: 10.1021/jacs.7b08640. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Manav N., Janaagal A., Gupta I.. Unveiling New Horizons: Exploring Rhenium and Iridium Dipyrrinato Complexes as Luminescent Theranostic Agents for Phototherapy. Coord. Chem. Rev. 2024;511:215798. doi: 10.1016/j.ccr.2024.215798. [DOI] [Google Scholar]
  7. Gutsche C. S., Hohlfeld B. F., Flanagan K. J., Senge M. O., Kulak N., Wiehe A.. Sequential Nucleophilic Substitution of the α-Pyrrole and p-Aryl Positions of Meso-Pentafluorophenyl-Substituted BODIPYs. Eur. J. Org. Chem. 2017;2017:3187–3196. doi: 10.1002/ejoc.201700264. [DOI] [Google Scholar]
  8. Shin J. Y., Patrick B. O., Dolphin D.. Facile Synthesis of Dicyanovinyl-Di­(Meso-Aryl)­Dipyrromethenes via a Dipyrromethene-DDQ Adduct. Org. Biomol. Chem. 2009;7:2032–2035. doi: 10.1039/b904446a. [DOI] [PubMed] [Google Scholar]
  9. Wood T. E., Thompson A.. Advances in the Chemistry of Dipyrrins and Their Complexes. Chem. Rev. 2007;107:1831–1861. doi: 10.1021/cr050052c. [DOI] [PubMed] [Google Scholar]
  10. Gutsche C. S., Gräfe S., Gitter B., Flanagan K. J., Senge M. O., Kulak N., Wiehe A.. Pre-/Post-Functionalization in Dipyrrin Metal Complexes-Antitumor and Antibacterial Activity of Their Glycosylated Derivatives. Dalt. Trans. 2018;47:12373–12384. doi: 10.1039/C8DT03059F. [DOI] [PubMed] [Google Scholar]
  11. Bhupathiraju N. V. S. D. K., Rizvi W., Batteas J. D., Drain C. M.. Fluorinated Porphyrinoids as Efficient Platforms for New Photonic Materials, Sensors, and Therapeutics. Org. Biomol. Chem. 2016;14:389–408. doi: 10.1039/C5OB01839K. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Pandey S. K., Gryshuk A. L., Graham A., Ohkubo K., Fukuzumi S., Dobhal M. P., Zheng G., Ou Z., Zhan R., Kadish K. M., Oseroff A., Ramaprasad S., Pandey R. K.. Fluorinated Photosensitizers: Synthesis, Photophysical, Electrochemical, Intracellular Localization, in Vitro Photosensitizing Efficacy and Determination of Tumor-Uptake by 19F in Vivo NMR Spectroscopy. Tetrahedron. 2003;59:10059–10073. doi: 10.1016/j.tet.2003.10.016. [DOI] [Google Scholar]
  13. Goslinski T., Piskorz J.. Fluorinated Porphyrinoids and Their Biomedical Applications. J. Photochem. Photobiol. C: Photochem. Rev. 2011;12:304–321. doi: 10.1016/j.jphotochemrev.2011.09.005. [DOI] [Google Scholar]
  14. Li G., Graham A., Potter W., Grossman Z. D., Oseroff A., Dougherty T. J., Pandey R. K.. A Simple and Efficient Approach for the Synthesis of Fluorinated and Nonfluorinated Octaethylporphyrin-Based Benzochlorins with Variable Lipophilicity, Their in Vivo Tumor Uptake, and the Preliminary in Vitro Photosensitizing Efficacy. J. Org. Chem. 2001;66:1316–1325. doi: 10.1021/jo001541+. [DOI] [PubMed] [Google Scholar]
  15. Werrett M. V., Wright P. J., Simpson P. V., Raiteri P., Skelton B. W., Stagni S., Buckley A. G., Rigby P. J., Massi M.. Rhenium Tetrazolato Complexes Coordinated to Thioalkyl-Functionalised Phenanthroline Ligands: Synthesis, Photophysical Characterisation, and Incubation in Live HeLa Cells. Dalt. Trans. 2015;44:20636–20647. doi: 10.1039/C5DT03470A. [DOI] [PubMed] [Google Scholar]
  16. Zhao Q., Huang C., Li F.. Phosphorescent Heavy-Metal Complexes for Bioimaging. Chem. Soc. Rev. 2011;40:2508–2524. doi: 10.1039/c0cs00114g. [DOI] [PubMed] [Google Scholar]
  17. Kassab G., Manav N., Pires L., Cheng M. H. Y., Mo Y., Buzzá H. H., Gupta I., Chen J., Zheng G.. Structural Effect of Rhenium- and Iridium-Complex Liposome Composition on Their Selectivity for Antimicrobial Photodynamic Therapy. Small Science. 2024;4:2300131. doi: 10.1002/smsc.202300131. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Chen Y., Heeg M. J., Braunschweiger P. G., Xie W., Wang P. G.. A Carbohydrate-Linked Cisplatin Analogue Having Antitumor Activity. Angew. Chem., Int. Ed. 1999;38:1768–1769. doi: 10.1002/(SICI)1521-3773(19990614)38:12<1768::AID-ANIE1768>3.0.CO;2-6. [DOI] [PubMed] [Google Scholar]
  19. Ma D. L., Shum T. Y. T., Zhang F., Che C. M., Yang M.. Water Soluble Luminescent Platinum Terpyridine Complexes with Glycosylated Acetylide and Arylacetylide Ligands: Photoluminescent Properties and Cytotoxicities. Chem. Commun. 2005;41(37):4675–4677. doi: 10.1039/b507114c. [DOI] [PubMed] [Google Scholar]
  20. Chen X., Hui L., Foster D. A., Drain C. M.. Efficient Synthesis and Photodynamic Activity of Porphyrin-Saccharide Conjugates: Targeting and Incapacitating Cancer Cells. Biochemistry. 2004;43:10918–10929. doi: 10.1021/bi049272v. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Manav N., Kesavan P. E., Ishida M., Mori S., Yasutake Y., Fukatsu S., Furuta H., Gupta I.. Phosphorescent Rhenium-Dipyrrinates: Efficient Photosensitizers for Singlet Oxygen Generation. Dalt. Trans. 2019;48:2467–2478. doi: 10.1039/C8DT04540B. [DOI] [PubMed] [Google Scholar]
  22. Pandey V., Raza M. K., Joshi P., Gupta I.. Synthesis of Water-Soluble Thioglycosylated Trans-A2B2Type Porphyrins: Cellular Uptake Studies and Photodynamic Efficiency. J. Org. Chem. 2020;85:6309–6322. doi: 10.1021/acs.joc.9b03491. [DOI] [PubMed] [Google Scholar]
  23. Manav N., Lone M. Y., Raza M. K., Chavda J., Mori S., Gupta I.. Luminescent Iridium­(III) Dipyrrinato Complexes: Synthesis, X-Ray Structures, and DFT and Photocytotoxicity Studies of Glycosylated Derivatives. Dalt. Trans. 2022;51:3849–3863. doi: 10.1039/D1DT04218A. [DOI] [PubMed] [Google Scholar]
  24. Manav N., Chavda J., Kidwai S., Singh R., Mori S., Gupta I.. Pd­(II)­Dipyrrinato Complexes: Synthesis, Crystal Structure and Their Antibacterial Applications. J. Porphyr. Phthalocyanines. 2023;27:1304–1312. doi: 10.1142/S108842462350089X. [DOI] [Google Scholar]
  25. McLean T. M., Moody J. L., Waterland M. R., Telfer S. G.. Luminescent Rhenium­(I)-Dipyrrinato Complexes. Inorg. Chem. 2012;51:446–455. doi: 10.1021/ic201877t. [DOI] [PubMed] [Google Scholar]
  26. Smithback J. L., Helms J. B., Schutte E., Woessner S. M., Sullivan B. P.. Preparative Routes to Luminescent Mixed-Ligand Rhenium­(I) Dicarbonyl Complexes. Inorg. Chem. 2006;45:2163–2174. doi: 10.1021/ic050707s. [DOI] [PubMed] [Google Scholar]
  27. Riese S., Holzapfel M., Schmiedel A., Gert I., Schmidt D., Würthner F., Lambert C.. Photoinduced Dynamics of Bis-Dipyrrinato-Palladium­(II) and Porphodimethenato-Palladium­(II) Complexes: Governing Near Infrared Phosphorescence by Structural Restriction. Inorg. Chem. 2018;57:12480–12488. doi: 10.1021/acs.inorgchem.8b00974. [DOI] [PubMed] [Google Scholar]
  28. Baudron S. A.. Dipyrrin Based Homo- and Hetero-Metallic Infinite Architectures. CrystEngComm. 2010;12:2288–2295. doi: 10.1039/c001020k. [DOI] [Google Scholar]
  29. Manav N., Kesavan P. E., Ishida M., Mori S., Yasutake Y., Fukatsu S., Furuta H., Gupta I.. Phosphorescent Rhenium-Dipyrrinates: Efficient Photosensitizers for Singlet Oxygen Generation. Dalt. Trans. 2019;48:2467–2478. doi: 10.1039/C8DT04540B. [DOI] [PubMed] [Google Scholar]
  30. Manav N., Chavda J., Bhatia D., Gupta I.. Thioglucose-Linked Pd­(II)­Dipyrrinates: Synthesis and Photodynamic Studies against Breast Cancer Cells. J. Porphyr. Phthalocyanines. 2025;29(10):1184–1189. doi: 10.1142/S1088424625501007. [DOI] [Google Scholar]
  31. Chavda J., Chavda V., Janaagal A., Singh U., Bhatia D., Gupta I.. Meso-Functionalized BODIPYs: Synthesis, Molecular Docking and Photodynamic Efficiency on Breast Cancer Cells. J. Porphyr. Phthalocyanines. 2023;27:390–397. doi: 10.1142/S1088424623500086. [DOI] [Google Scholar]
  32. Pandey V., Raza M. K., Sonowal M., Gupta I.. BODIPY Based Red Emitters: Synthesis, Computational and Biological Studies. Bioorg. Chem. 2021;106:104467. doi: 10.1016/j.bioorg.2020.104467. [DOI] [PubMed] [Google Scholar]
  33. Chavda J., Siwach A., Sabharwal S., Janaagal A., Bhatia D., Gupta I.. BODIPYS Based Fluorescent Markers To Monitor Autophagic Lysosomes and Lipid Droplets in TNBC. ACS Med. Chem. Lett. 2024;15:2115–2120. doi: 10.1021/acsmedchemlett.4c00275. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Chavda J., Rajwar A., Bhatia D., Gupta I.. Synthesis of Novel Zinc Porphyrins with Bioisosteric Replacement of Sorafenib: Efficient Theranostic Agents for Anti-Cancer Application. J. Inorg. Biochem. 2023;249:112384. doi: 10.1016/j.jinorgbio.2023.112384. [DOI] [PubMed] [Google Scholar]
  35. Kesavan P. E., Pandey V., Raza M. K., Mori S., Gupta I.. Water Soluble Thioglycosylated BODIPYs for Mitochondria Targeted Cytotoxicity. Bioorg. Chem. 2019;91:103139. doi: 10.1016/j.bioorg.2019.103139. [DOI] [PubMed] [Google Scholar]
  36. Liu H., Schreiber S. L., Stockwell B.R.. Targeting dependency on the GPX4 lipid peroxide repair pathway for cancer therapy. Biochemistry. 2018;57:2059–2060. doi: 10.1021/acs.biochem.8b00307. [DOI] [PMC free article] [PubMed] [Google Scholar]

Associated Data

This section collects any data citations, data availability statements, or supplementary materials included in this article.

Supplementary Materials

ml6c00168_si_001.cif (4.1MB, cif)
ml6c00168_si_002.pdf (156.1KB, pdf)
ml6c00168_si_003.pdf (1.2MB, pdf)

Articles from ACS Medicinal Chemistry Letters are provided here courtesy of American Chemical Society

RESOURCES