Chlorine Derivatives Research Articles

NBS-Mediated C(sp2)-H Bond Chlorination of Enaminones: Using DCE as Chlorine Source

Commercial DCE is excavated as both a “Cl” source and a solvent for the vinyl C(sp2)-H chlorination. The strategy involves a metal-free NBS-mediated C(sp2)-H chlorination of enaminones, and affords diverse, functionalized α-chlorinated enaminones with a Z-configuration. This mild and effective approach not only advances the vinyl C(sp2)-H chlorination, employing DCE as the “Cl” source, but also provides a new strategy for accessing chlorinated enaminone derivatives.

Unveiling the potent Antimicrobial Photodynamic Therapy in Gram-positive and Gram-negative bacteria – Water remediation with monocharged chlorins

Water pollution is a significant concern worldwide, and it includes contaminants such as antibiotic-resistant pathogens. Antimicrobial photodynamic therapy (aPDT) offers a non-invasive and non-toxic alternative for the inactivation of these microorganisms. So, this study reports the synthesis, structural characterisation, photophysical properties, and aPDT efficacy of cationic free-base and zinc(II) chlorin (Chl) derivatives bearing N,N-dimethylpyrrolydinium groups (H2Chl 1a and ZnChl 1b). The aPDT assays were performed against two bacterial models: Staphylococcus aureus (Gram-(+)) and Escherichia coli (Gram-(–)). The H2Chl 1a and ZnChl 1b distinct’s solubility profile, coupled with their ability to generate singlet oxygen (1O2) under light exposure, (H2Chl 1a, ФΔ = 0.58 <TPP, ФΔ = 0.65 < ZnChl 1b, ФΔ = 0.83) opens up their potential application as photosensitizers (PS) in aPDT. The effectiveness of H2Chl 1a and ZnChl 1b at 1.0 and 5.0 μM in aPDT against S. aureus and E. coli at 500 W.m–2 (total exposure time: 60 –120 min) showed a viability reduction > 6.0 log10 CFU.mL–1. Additionally, KI was used as a coadjuvant to potentiate the photoinactivation of E. coli, reaching the method’s detection limit (> 4.0 log10 RLU). As most of the PS developed to inactivate Gram-negative bacteria are cationic with three or more charges, the fact that the H2Chl 1a and ZnChl 1b with only one cationic charge photoinactivate E. coli at low concentrations and with a reduced light dose, it is an importing discovery that deserves further exploration. These monocharged chlorin dyes have the potential for water remediation.

Synthesis of potential anticonvulsants based on chloral hydrate and carbamazepine: their spectral characteristics and in silico ADME profiling

This paper reports the synthesis of a new potential anticonvulsant, N-(2,2,2-trichloro-1-hydroxyethyl)-5H-dibenzo[b,f]azepine-5-carboxamide. Its synthesis is based on condensing the anticonvulsant drug carbamazepine with chloral hydrate used in medical practice. The reaction was carried out in a melt or by boiling in dry benzene with the removal of the resulting water from the reaction medium. The product was obtained with yields of 88 and 79%, respectively. Replacing the hydroxyl group in the resulting condensation product with an amino group led to the formation of N-(1-amino-2,2,2-trichloroethyl)-5H-dibenzo[b,f]azepine-5-carboxamide. This synthesis was carried out in two stages. Initially, the hydroxy derivative was chlorinated with thionyl chloride. Then, by treating the resulting chlorine derivative with an aqueous solution of ammonia (25%) in MTBE medium, the target product was obtained. The structure of the obtained compounds was proven by 1H NMR and IR spectroscopy data. The SwissADME online platform showed that the synthesized compounds should have high bioavailability as well as moderate solubility in water and be able to penetrate the blood-brain barrier.

Synthesis and Spatial Structure of 3-Phenylacrylic Acid Octahydroquinolizin-1-Ylmethyl Ester and 2-(Octahydroquinolizin-1-Ylmethyl)Isoindole-1,3-Dione

The reactions of lupinine alkaloid and its chlorine derivative with cinnamoyl chloride and 2-K-isoindole-1,3-dione were investigated to obtain 3-phenylacrylic acid octahydroquinolizin-1-ylmethyl ester and 2-(octahydroquinolizin-1-ylmethyl)isoindole-1,3-dione, respectively. The optimal conditions for carrying out the aforementioned reactions were determined, taking into account the nature of the solvent and medium. It was established that acylation of the molecule in a benzene medium, in the presence of trimethylamine, resulted in the formation of 3-phenylacrylic acid octahydroquinolizin-1-ylmethyl ester, with an 82% yield. It was demonstrated that the interaction of chlorolupinine with 2-K-isoindole-1,3-dione under Gabriel reaction conditions resulted in the formation of 2-(octahydroquinolizin-1-ylmethyl)isoindole-1,3-dione. The conformer with an axial orientation of the isoindole-1,3-dione substituent was observed to exhibit greater stability than the conformer with an equatorial orientation. The structure of the synthesized compounds was investigated by IR, 1H, and 13C NMR spectroscopy. The use of two-dimensional spectra in COSY (1H-1H) and HMQC (1H-13C) formats enabled the establishment of homo- and heteronuclear interactions, thereby confirming the structure of the compounds under investigation. The values of chemical shifts, multiplet and integrated intensity of 1H and 13C signals in one-dimensional NMR spectra of the novel compounds were determined. The crystal structures of 3-phenylacrylic acid octahydroquinolizin-1-ylmethyl ester and 2-(octahydroquinolizin-1-ylmethyl)isoindole-1,3-dione were elucidated through X-ray analysis.

Structural Studies of Piperidino‐Alanes with Halide, Amide and Hydride as further Ligands at Aluminum

AbstractNine different derivatives of piperidino alanes of the general formula (CH2)5N‐AlXY [X=Y=Cl (1), Br (2), I (3); X=(CH2)5N, Y=Cl (4), Br (5), I (6); X=H, Y=Cl (7), Br (8), I (9)] have been synthesized and compared with respect to their structures. All molecules form dimers with an Al2N2 central cycle and aluminum and nitrogen atoms in distorted tetrahedral environments as determined from X‐ray diffraction. The three dihalide derivatives 1, 2 and 3 have C2h (2/m) symmetries in solution of which they maintain the Centro symmetry in the crystal lattice. The bis(piperidino) derivatives 4, 5 and 6 have either C1 (1) symmetry with the bridging piperidino cycles oriented in the same direction (4, 5) or Ci (ī) point symmetry as found for 6 (in solution at least one other isomer is present). Whereas the chlorine derivative 7 has crystallographic Ci (ī) symmetry, the bromine 8 has almost C2 and the iodine 9 crystallographic C2 (2) point symmetry. In solution all derivatives 7, 8, 9 show equilibria between cis (C2) and trans (Ci) isomeric forms (27Al NMR). The longest Al−N bond lengths within the rings are found for 5 (1.969(4) Å) and the shortest for 8 (1.940(4) Å). The ratio of Al⋅⋅⋅Al to N⋅⋅⋅N non‐bonding distances in the almost square rings vary with the bulkiness of the terminal ligands at aluminum.

Experimental and clinical combined photodynamic therapy for malignant and premalignant lesions using various types of radiation

The aim of the study was to present various types of radiation that can increase the effectiveness of combined photodynamic therapy (PDT) for malignant and premalignant lesions. Material and Methods. The Web of Science, Scopus, MedLine, Library, and RSCI databases were used for finding publications on this topic, mainly over the last 10 years. Of 230 sources, 64 were included in the review. Results. Photodynamic therapy is a new cancer treatment technology that has become increasingly popular in recent years. It is often an alternative method of treating cancer when there is a high risk of side effects and complications during traditional treatments such as surgery, radiation therapy and chemotherapy. PDT requires a photosensitizer, light energy, and oxygen to create reactive oxygen species that destroy cancer cells. This review examines the basic principles and mechanisms of PDT used alone and in combination with other traditional therapies. Despite the fact that PDT is an effective and non-invasive cancer treatment, it has some limitations, such as low light penetration depth, ineffective photosensitizers and tumor hypoxia. Our study examines new strategies that use other energy sources, such as infrared- and x-rays, ultrasound, as well as electric and magnetic fields, to enhance the PDT effect and overcome its limitations. Great hopes are also associated with the use of a combination of PDT and neutron capture therapy (NСT). Currently, chlorin derivatives associated with boron carriers have been developed. They can be used for both fluorescence diagnostics and PDT, as well as for NСT. The synthesized compounds have a high selectivity of accumulation in the tumor. To date, encouraging preclinical results of high efficiency of combined use of NСT and PDT have already been obtained. Conclusion. Combination with various energy sources is a key factor for further development of PDT. Future research aimed at overcoming the limitations of PDT will contribute to unlocking the full potential of this technology in clinical practice.

Design, synthesis, characterization, and docking studies of hiherto unkown chlorinated thiazolidine, thiophene, and 2-iminochromene derivatives as protein-like protease inhibitors

Design, synthesis, characterization, and docking studies of hiherto unkown chlorinated thiazolidine, thiophene, and 2-iminochromene derivatives as protein-like protease inhibitors

Experimental study on alkylation of PCl3 for methyl-dichloride phosphine synthesis using mass spectrometry detection

An online sampling and mass spectrometry (MS) detection method was developed to study the alkylation of PCl3 with methane at high temperature for synthesis of methyl-dichloride phosphine (CH3PCl2, MDP), which was a free radical reaction on a millisecond time scale. Through qualitative analysis, the byproducts P4 and chloro-dimethyl-phosphine ((CH3)2PCl, CDMP) were identified, with their formation mechanisms elucidated for the first time. The effects of operation conditions, including temperature, residence time, and types and concentrations of chloromethanes (CH4-xClx, x = 2, 3, 4), on both MDP yield and selectivity, were systematically investigated. The optimal operation conditions were determined based on MDP yield and selectivity. The addition of chloromethanes significantly enhanced PCl3 conversion. Chloromethanes underwent conversion in the reaction, promoting PCl3 conversion while also continuously converting into lower chlorinated methane derivatives. These results are of great significance for guiding rational industrial process development.

Effectiveness of laser pulsed irradiation for antimicrobial photodynamic therapy

The aim of this study was to compare two types of light irradiation devices for antimicrobial photodynamic therapy (aPDT). A 660-nm light-emitting diode (LED) and a 665-nm laser diode (LD) were used for light irradiation, and 0.1 mg/L TONS 504, a cationic chlorin derivative, was used as the photosensitizer. We evaluated the light attenuation along the vertical and horizontal directions, temperature rise following light irradiation, and aPDT efficacy against Staphylococcus aureus under different conditions: TONS 504 only, light irradiation only, and TONS 504 with either LED (30 J/cm2) or LD light irradiation (continuous: 30 J/cm2; pulsed: 20 J/cm2 at 2/3 duty cycle, 10 J/cm2 at 1/3 duty cycle). Both LED and LD light intensities were inversely proportional to the square of the vertical distance from the irradiated area. Along the horizontal distance from the nadir of the light source, the LED light intensity attenuated according to the cosine quadrature law, while the LD light intensity did not attenuate within the measurable range. Following light irradiation, the temperature rise increased as the TONS 504 concentration increased in the order of pulsed LD < continuous LD < LED irradiation. aPDT with light irradiation only or TONS 504 only had no antimicrobial effect, while aPDT with TONS 504 under continuous or pulsed LD light irradiation provided approximately 3 log reduction at 30 J/cm2 and 20 J/cm2 and approximately 2 log reduction at 10 J/cm2. TONS 504-aPDT under pulsed LD light irradiation provided anti-microbial effect without significant temperature rise.

The influence of the chlorine atom on the biological activity of 2′-hydroxychalcone in relation to the lipid phase of biological membranes - Anticancer and antimicrobial activity

The study investigates the effect of the presence of a chlorine atom in the 2′-hydroxychalcone molecule on its interaction with model lipid membranes, in order to discern its potential pharmacological activity. Five chlorine derivatives of 2′-hydroxychalcone were synthesized and evaluated against liposomes composed of POPC and enriched with cationic (DOTAP) or anionic (POPG) lipids. The physicochemical properties of the compounds were initially simulated using SwissAdame software, revealing high lipophilicity (ilogP values: 2.79–2.90). The dynamic light scattering analysis of liposomes showed that chloro chalcones induce minor changes in the diameter of liposomes of different surface charges. Fluorescence quenching assays with a TMA-DPH probe demonstrated the strong ability of the compounds to interact with the lipid bilayer, with varying quenching capacities based on chlorine atom position. FTIR studies indicated alterations in carbonyl, phosphate, and choline groups, suggesting a transition area localization rather than deep penetration into the hydrocarbon chains. Additionally, dipole potential reduction was observed in POPC and POPC-POPG membranes, particularly pronounced by derivatives with a chlorine atom in the B ring. Antibacterial and antibiofilm assays revealed enhanced activity of derivatives with a chlorine atom compared to 2′-hydroxychalcone, especially against Gram-positive bacteria. The MIC and MBIC50 values showed increased efficacy in the presence of chlorine with 3′-5′-dichloro-2′-hydroxychalcone demonstrating optimal antimicrobial and antibiofilm activity. Furthermore, antiproliferative assays against breast cancer cell lines indicated higher activity of B-ring chlorine derivatives, particularly against MDA-MB-231 cells. In general, the presence of a chlorine atom in 2′-hydroxychalcone improves its pharmacological potential, with derivatives showing improved antimicrobial, antibiofilm, and antiproliferative activities, especially against aggressive breast cancer cell lines. These findings underscore the importance of molecular structure in modulating biological activity and highlight chalcones with a chlorine as promising candidates for further drug development studies.

Exploring the spectral properties and potential applications of dimethylamine-modified porphyrin and chlorin dyes

The synthesis, structural characterization, and optical properties of new free-base and metalated dimethylamine-based porphyrin (1, 1a) and chlorin (2, 2a) derivatives are presented. The synthetic approach is based on the peripheral substitution of the para-fluor atoms of the commercially available 5,10,15,20-tetrakis(pentafluorophenyl)-21H,23H-porphyrin (H2TPPF20) by dimethylamine (H2Por 1), following the preparation of the analogous chlorin dye (H2Chl 2) using N-methylglycine and p-formaldehyde. Both compounds were then metalated with zinc acetate to perform the corresponding ZnPor 1a and ZnChl 2a dyes. Several photophysical parameters were determined, including absorption and emission features at 298 K (e.g., molar absorptivity coefficients, λ absorption maxima of Soret and/or Q bands, λemission maxima, and ratio of long- to short-wavelength emission intensity), fluorescence quantum yield (ФF), stability (under dark conditions), and photostability (under white light exposure at irradiance of 50 mW.cm−2). The photophysical results were determined and compared for the type of meso-substituted scaffold selected – A4-type – of free-base (1, 2) and zinc(II) complex (1a, 2a). The four compounds exhibit high dark stability in DMF (absorption reduction intensity < 3 %). The Pors 1 and 1a have also high photostability (absorption reduction intensity < 1.5 %), but H2Chl 2 and ZnChl 2a present a considerable absorption reduction, 14.3 % and 22.3 %, respectively. The ФF of the ZnPor 1a (ФF = 0.02) and H2Por 1 (ФF = 0.02) are lower than those of ZnChl 2a (ФF = 0.06) and H2Chl 2 (ФF = 0.09). The developed compounds present potential applications in nonlinear optics, biomarkers, and/or solar cells.

Benastatin K, a chlorinated benastatin-related antibiotic from Streptomyces sp. HGTA384.

Benastatin K (1), a new chlorinated benastatin derivative, was isolated from the culture broth of the actinomycete Streptomyces sp. HGTA384. The structure of 1 was determined on the basis of spectroscopic analysis, including 1D and 2D NMR, as well as HRESI-MS, UV and IR, and comparison with data reported in the literature. Compound 1 and benastatins A and B exhibited inhibitory activity against Micrococcus luteus (MIC 7.8, 31.3, and 3.9 μM, respectively), and IgE-mediated β-hexosaminidase release in RBL-2H3 cells with IC50 values of 42, 79, and 19 μM, respectively.

Chlorin spiro-Tröger's base as a prospective photosensitizer for photodynamic therapy of cancer

Octahydroxy bis-porphyrin Tröger's base (TB) and octahydroxy porphyrin-chlorin spiro-Tröger's base (spiroTB) derivatives were successfully prepared from their Ni(II) complexes utilizing an optimized demetalation method using H2SO4-TFA followed by demethylation via BBr3. The synthesized TB and spiroTB were then in in vitro experiments for their utility in photodynamic therapy (PDT) of cancer. Compared to temoporfin (mTHPC, Foscan®), the chlorin derivative used in PDT of cancer, TB and spiroTB were localized in lysosomes instead of the endoplasmic reticulum and were found to possess enhanced biocompatibility. Cell culture studies were performed on TRAMP-C2 (prostate cancer), HeLa (cervical cancer), and MRC-5 (non cancerous) cell lines. Both TB and spiroTB displayed negligible dark toxicity but increased production of reactive oxygen species (ROS) when illuminated. In addition, spiroTB displayed significant phototoxicity in TRAMP-C2 cells (IC50, light 0.7 μM after 24 h incubation). Despite the phototoxicity of spiroTB being lower than that of mTHPC (IC50, light 0.02 μM), due to the low dark toxicity (IC50, dark > 100 μM), the therapeutic factor of spiroTB (>150) is six times higher than that of mTHPC (25).

Electrochemical, gravimetric, quantum chemical and computational investigations on an effective synthetic chlorinated cyclic imide derivative as a corrosion inhibitor for carbon steel in sulfuric acid solution

Although many different human activities such as the oil and gas sector, mineral production, utilities, transportation, etc. depend on the utilization of steel and its alloys, they are highly susceptible to corrosion, especially in acidic media. Hence, processing entails substantial material expenditures due to metal losses. In this regard, the inhibitory characteristics of the synthetic heterocyclic derivative (3aR,7S,7aS)-4,5,6,7,8,8-hexachloro-1,3-dioxo-1,3,3a,4,7,7a-hexahydro-2H-4,7-methanoisoindol-2-yl)benzenesulfonamide (MBSI) was studied against corrosion of C-steel in 0.5 M H2SO4 at 25-55 °C. The structure of the synthesized molecule was confirmed by FTIR, 1H-NMR, 13C-NMR, and MS. Weight-loss, potentiodynamic polarization, electrochemical impedance spectroscopy, electrochemical frequency modulation measurements as well as theoretical analyses were employed in this investigation. The results showed that the investigated MBSI compound functions as an efficient inhibitor with a physical adsorption nature on the surface of carbon steel. MBSI concentration causes the inhibition efficiency to rise, reaching a maximum of 94% for the steel alloy corrosion at 37 × 10−6 M and 25°C. The synthesized compound was suggested to act as a mixed-type inhibitor. SEM surface analysis showed the construction of a protective layer at the carbon steel surface. DFT-based quantum chemical indices provided more insight into the inhibitory mechanism. Molecular dynamics (MD) simulations were also applied to predict the conformational adsorption change of the inhibitor on the iron surface. In addition, thermodynamic and kinetic parameters were calculated. The experimental results are largely consistent with the theoretical results.

Photodynamic Therapy Using RGD-Functionalized Quantum Dots Elicit a Potent Immune Response in a Syngeneic Mouse Model of Pancreatic Cancer.

Photodynamic therapy (PDT) induces anti-tumor immune responses by triggering immunogenic cell death in tumor cells. Previously, we demonstrated that novel QDs-RGD nanoparticles exhibited high efficiency as photosensitizers in the treatment of pancreatic cancer. However, the underlying mechanism of the anti-tumor immune effects induced by the photosensitizer remains unknown. This study assessed the anticancer immune effect of QDs-RGD, as well as the conventional photosensitizer chlorine derivative, YLG-1, for comparison, against pancreatic cancer in support of superior therapeutic efficacy. The pancreatic cancer cell line, Panc02, was used for in vitro studies. C57BL/6 mice bearing pancreatic cancer cell-derived xenografts were generated for in vivo studies to assess the anti-tumor effects of QDs-RGD-PDT and YLG-1-PDT. The immunostimulatory ability of both photosensitizers was examined by measuring the expression of damage-associated molecular patterns (DAMP), such as calreticulin (CRT), assessing dendritic cell (DC) maturation, and analyzing cytokine expression. The specific immunity of QDs-RGD and YLG-1-PDT on distant tumor were determined by combining PDT with anti-CTLA-4 antibody. QDs-RGD-PDT and YLG-1-PDT significantly inhibited pancreatic cancer cell growth in a dose- and time-dependent manner. While both photosensitizers significantly promoted CRT release, DC maturation, and interferon γ (IFN-γ) and tumor necrosis factor α (TNF-α) expression, QDs-RGD exerted a stronger immunostimulatory effect than YLG-1. Combination treatment with QDs-RGD and CTLA-4 blockade was able to significantly inhibit the growth of distant tumors. QDs-RGD is a novel and effective PDT strategy for treating pancreatic tumors by inducing anti-tumor immune responses.

Раскрытие экзоцикла форбинов слабыми О-нуклеофилами. Изучение и оптимизация путей синтеза свободного хлорина е6

The article considers issues concerning the reaction of exocycle opening in phorbin molecules (on the example of methylpheophorbide a) under the O nucleophiles - water and alcohols action. According to the author, under certain conditions relatively weak nucleophiles as water and alcohols can cause the opening of the exocycle in the molecule of methylpheophorbide a with the formation of chlorine derivatives e6. The study of this reaction, in addition, reveals new synthetic methods to obtain chlorine e6 esters of different degrees of substitution, and eventually - free chlorine e6 in the form of triacids. Free chlorine is a valuable photosensitiser for photodynamic therapy (PDT), and a starting compound for the preparation of other photosensitizers. The article also discusses possible synthetic approaches to obtain free chlorine e6.

Opening of forbinexocycle by weak O-nucleophiles. Study and optimisation of free chlorine e6 synthesis methods

The article considers issues concerning the reaction of exocycle opening in phorbin molecules (on the example of methylpheophorbide a) under the O nucleophiles - water and alcohols action. According to the author, under certain conditions relatively weak nucleophiles as water and alcohols can cause the opening of the exocycle in the molecule of methylpheophorbide a with the formation of chlorine derivatives e6. The study of this reaction, in addition, reveals new synthetic methods to obtain chlorine e6 esters of different degrees of substitution, and eventually - free chlorine e6 in the form of triacids. Free chlorine is a valuable photosensitiser for photodynamic therapy (PDT), and a starting compound for the preparation of other photosensitizers. The article also discusses possible synthetic approaches to obtain free chlorine e6.

Institute of Chemistry, Chernyshevsky Saratov State University

New test tools made of nanofibers based on polyamide-6 (PA-6) for the sorption preconcentration of some phenols as their azo derivatives followed by colorimetric determination are obtained. Approaches to the derivatization of phenol and chlorine derivatives by azo coupling with 4-nitrophenyldiazonium and oxidative condensation with 4-aminoantipyrine for improving the sorption characteristics of the studied phenols are proposed. The efficiency of the two derivatization methods is compared. The sorption kinetics of phenol and 2-chlorophenol derivatives and the effect of pH on the nature of their sorption are studied. The features of the sorption of phenol derivatives on nonwoven materials and the corresponding sorption isotherms are interpreted. Examples of the quantitative assessment of the concentration of phenols in aqueous media by the mathematical processing of digital images of the colored areas of test tools are presented. It is shown that the proposed methods can be used for the determination of phenol and 2-chlorophenol with the preconcentration of their derivatives on a PA-6 nanofiber in the range 0.2–1.0 μM (≈0.02–0.09 mg/L for phenol, ≈0.03–0.13 mg/L for 2-chlorophenol) with an error of colorimetric determination of no more than 20% (MAChshld phenol is 0.001 mg/L for the amount of volatile phenols in water bodies, provided that water is disinfected with chlorine; in other cases, the MAC is 0.1 mg/L).

Geometry-Independent Ultrafast Energy Transfer in Bioinspired Arrays Containing Electronically Coupled BODIPY Dimers as Energy Donors.

In photosynthetic light-harvesting complexes, strong interaction between chromophores enables efficient absorption of solar radiation and has been suggested to enable ultrafast energy funneling to the reaction center. To examine whether similar effects can be realized in synthetic systems, and to determine the mechanisms of energy transfer, we synthesized and characterized a series of bioinspired arrays containing strongly-coupled BODIPY dimers as energy donors and chlorin derivatives as energy acceptors. The BODIPY dimers feature broad absorption in the range of 500-600 nm, complementing the chlorin absorption to provide absorption across the entire visible spectrum. Ultrafast (~10 ps) energy transfer was observed from photoexcited BODIPY dyads to chlorin subunits. Surprisingly, the energy-transfer rate is nearly independent of the position where the BODIPY dimer is attached to the chlorin and of the type of connecting linker. In addition, the energy-transfer rate from BODIPY dimers to chlorin is slower than the corresponding rate in arrays containing BODIPY monomers. The lower rate, corresponding to less efficient through-bond transfer, is most likely due to weaker electronic coupling between the ground state of the chlorin acceptor and the delocalized electronic state of the BODIPY dimer, compared to the localized state of a BODIPY monomer.

Peptide-Targeted Photosensitisers: Synthesis and Applications in Photobiology

The conjugation of porphyrin derivatives to peptide ligands is a valuable strategy for enhancing their aqueous solubility and tissue selectivity in the photodynamic therapy (PDT) of cancer. To this end, bioorthogonal ligation (“click”) chemistries provide an efficient way to link porphyrins and other tetrapyrrole systems with complementary multifunctional peptides. We will describe some of our work in this area towards the generation of specific targeted conjugates between porphyrin and chlorin derivatives and tumour-homing or cell-penetrating peptide carriers [1, 2]. Linking otherwise hydrophobic photosensitisers to cationic cell-penetrating peptides (e.g. HIV Tat 48-57) provides amphiphilic derivatives with improved water solubility plus enhanced cellular uptake and predictable sub-cellular localisation. Such molecules are very suitable for use in the light-triggered delivery of macromolecular therapeutics by photochemical internalisation (PCI), which will be illustrated for the targeted delivery of the protein toxin, saporin [3].Peptide targeting strategies are also valuable for PDT with 5-aminolevulinic acid (ALA) [4]. In ALA-PDT, administered ALA is converted within cells via the heme biosynthetic pathway to protoporphyrin IX which may then be exploited as a photosensitiser. In this context, we will present some recent chemical and biological data on the application of peptide targeting for the enhanced delivery of multiple ALA units to specific cell types [5].