Chemical Communications Blog

Antibodies emerge as a key player for disease detection and biologics due to its specificity of interaction and high binding affinity at target site. The application site for antibodies restricted to extracellular compartment as it has a poor plasma membrane permeability. Vehicles for direct intracellular delivery of antibodies are an extremely important alternative approach and various route have been explored including nanocarriers, liposomes, cell-penetrating peptides (CPPs). For most of these cases, loss of protein activity due to endolysosomal trapping or loss of protein activity lowers the efficacy of the antibody. So, it is highly desirable to formulate a fabrication strategy that is easily operable and antibody can be directly delivered to cytosol. In this aspect, cell-penetrating poly(disulfide)s (CPDs) which consist of disulfide polymer backbone with arginine-rich side chains permits thiol-mediated cellular uptake, which is insensitive to endocytosis inhibition, ensuing an efficient cytosolic availability. A team of researcher from Zhejiang University of China, reported a pH-responsive monomer to form new CPDs for enhanced intracellular delivery of antibodies into cancer cells. They tried to explore the stimuli responsiveness (lower pH) of tumor environment compared to healthy cells.

They have replaced the positively charged arginine moiety with neutral imidazole-based side chains. The resulting neutral CPD converts to positive charge upon protonation of the imidazole groups in acidic tumor environment. The advantage of charge reversal is easier cellular uptake by a combination of thiol-mediated and counter ion-activated uptake without significant endosomal trapping. The authors used a GSH-controlled NIR probe labelled at the N-terminal of the cargo protein so that the CPD could insert the cell followed by spectroscopic signal activation. Live-cell imaging of cancer cells using confocal laser scanning microscopy (CLSM) showed higher green fluorescence at pH 6.5 using IgG^FITC-CPD_IMD than neutral pH. This suggests higher uptake of imidazole based CPDs into cancer cells.

Fig2: In-vivo results show long-term effect by using the synthesized conjugate

For in-vivo experiments, the authors used GSH-activatable NIR fluorophore DCM-NH₂ and attached it to CPD_IMD. In vivo imaging of mice after intratumoral injection of the conjugate shows fluorescence signal at 1 h, that became stronger at 4 h, which indicate high drug dose accumulation at the tumor site. Both live-cell and in vivo results showed the great potential of this strategy for trackable and cancer-selective protein delivery with immediate cytosolic bioavailability. This new class of CPDs are expected to open an efficient platform for future cancer theranostics.

For details, please follow the article Chem. Commun., 2022, 58, 1314

About the blogger:

Dr Damayanti Bagchi is a postdoctoral researcher at University of California, Los Angeles, United States. She has obtained her PhD in Physical Chemistry from Satyendra Nath Bose National Centre for Basic Sciences, India. Her research is focused on spectroscopic studies of nano-biomaterials. She is interested in exploring light enabled therapeutics. She enjoys travelling and experimenting with various cuisines, which she found resembles with products/ side products of chemical reactions!

You can find her on Twitter at @DamayantiBagchi.

Cellulose nanofibers (CNFs) are used in large amounts in the paper and biomedical industry. The synthesis process, the nature of the catalyst used, and the recyclability of the catalyst has a direct impact on the cost effectiveness of industrial grade CNFs. CNF production follows carboxylation of the primary alcohol groups at the surface of the cellulose fibres mediated by catalyst 2,2,6,6-tetramethyl-1-piperidine-N-oxy radicals (TEMPO). The genotoxic nature of TEMPO suggests the requirement of a lower concentration of the catalyst used during the reaction.

Scheme for different synthesis strategies and characterization of TEMPO mediated CNFs.

Researchers across the world tried a green synthetic approach for CNFs preparation. This also includes successful removal of the catalyst from the product after completion of the reaction. One of the processes employs oxidation of wood pulp fibres using the magnetically recoverable Karimi’s catalyst (TEMPO@SiO2@Fe3O4). The products obtained using the modified catalyst is 5 nm thick cellulose nanofibrils like those obtained in the oxidation mediated by TEMPO in solution. Whereas, the catalyst was easily recovered with a magnet and successfully reused in 4 successive reaction cycles.

Differently modulated TEMPO like SiliaCat TEMPO (a commercial immobilized TEMPO catalyst) and others, show that hybrid sol–gel catalyst allows the synthesis of insoluble polysaccharide nanofibers of superior quality, eliminating waste.

New production strategies involve TEMPO-mediated oxidation followed by homogenisation. The residual hypochlorite can be quenched with 0.3% ascorbic acid to produce chloride and subsequently CNF is separated from the solid catalyst via simple filtration. This dramatically reduced the polysaccharide nanofiber production costs opening the route to large-scale production of functional products where their use has been limited by high cost.

For details: please visit https://pubs.rsc.org/en/content/articlelanding/2021/sc/d1sc03114g

About the blogger:

Dr. Damayanti Bagchi is a postdoctoral researcher in Irene Chen’s lab at University of California, Los Angeles, United States. She has obtained her PhD in Physical Chemistry from Satyendra Nath Bose National Centre for Basic Sciences, India. Her research is focused on spectroscopic studies of nano-biomaterials. She is interested in exploring light enabled therapeutics. She enjoys travelling and experimenting with various cuisines.

You can find her on Twitter at @DamayantiBagchi.

Carbazole based polycyclic aromatic hydrocarbon (PAH) are considered as an important material for organic LED applications. The scalable synthetic approach for PAH still lacks efficiency due to the formation of unwanted by-products. The other issues are often related to high cost of catalysts, harsh reaction condition and multi-step methods. In this aspect, researchers from Indian Institute of Technology Kharagpur, developed a transition metal-free rapid protocol for structurally versatile PAHs.

They have employed a Brønsted acid catalyst for the one pot cascade benzannulation strategy. The reported method allows conjugation of densely functionalized aromatic entities. The first step involves coupling reaction between unprotected 2-arylindoles (nucleophile) and benzyloxy/hydroxy aldehydes (electrophile) in the presence of an inexpensive Brønsted acid catalyst (Scheme1). The course of reaction proceeds through a pinacol-type rearrangement followed by an intramolecular nucleophilic addition leading to poly-aryl benzo[a]carbazole (B[a]C) formation.

After optimizing this step, they have attempted fabrication of carbazole based PAHs with extensive annulated p-conjugation. 2,3-Dichloro-5,6-dicyano-1,4-benzoquinone system (DDQ/H+) served as an excellent oxidant for the C–C bond forming reactions due to its high oxidation potential. The oxidative coupling reaction in the anhydrous dichloromethane solvent under an inert atmosphere, stiches number of aryl units together depending upon stoichiometry of DDQ. Appropriate ratio of DDQ and precursors in one-pot generate a challenging ‘‘six–seven–six’’ tricyclic-fused system (Scheme2).

The photophysical characterization suggests B[a]C systems show solvent polarity dependent fluorescence quantum yield. The highly emissive property of these molecules is beneficial for future OLED applications.

For details, please check: Chem. Commun., 2021,57, 5762-5765

About the blogger:

Dr. Damayanti Bagchi is a postdoctoral researcher in Irene Chen’s lab at University of California, Los Angeles, United States. She has obtained her PhD in Physical Chemistry from Satyendra Nath Bose National Centre for Basic Sciences, India. Her research is focused on spectroscopic studies of nano-biomaterials. She is interested in exploring light enabled therapeutics. She enjoys travelling and experimenting with various cuisines. You can find her on Twitter at @DamayantiBagchi.

Crystalline MOF structures with high porosity serve well for a range of applications including shape selective catalysis, gas storage or capture, and drug delivery. These entail the prominence of new methodologies for the synthesis of MOFs, either with unusual metal ion oxidation states or already existing molecular counterparts. In this vein, researchers from TU Denmark have used a ligand transferability strategy for the reaction of homoleptic carbonyl complexes of the Group 6 elements, M(CO)₆ (M = Cr, Mo, W), with neutral bridging ligands for the formation of heteroleptic M(CO)_6-nL_n complexes. For the first time, they have presented the synthesis and characterization of a series of MOFs obtained from M(CO)₆ (M = Cr, Mo, W) through the substitution of the ditopic pyrazine (pyz) ligand.

Scheme 1: Synthesis of Cr, Mo, and W.

The synthesis follows reaction at an elevated temperature between M(CO)₆ (M = Cr, Mo, W) and an excess of the pyz ligand in a sealed ampoule (Scheme1), leading to dark coloured crystalline products. The reaction is highly favourable for the Mo complex, due to the low dissociation energy of the first Mo–CO bond (119 kJ mol^-1), and a reaction temperature of 150°C produced a high yield of crystals. The same reaction conditions provided a minute amount of product for M = Cr and no indication of reactivity for M = W. However, a higher temperature of 200°C lead to the production of the W complex due to the high dissociation energy of the W-CO bond (142 kJ mol^-1).

The single-crystal X-ray diffraction pattern of the dark shiny crystals suggests that the composition is fac-M(CO)₃(pyz)_3/2.1/2 pyz (with M = Cr, Mo, W) (Fig. 1). Cr and Mo crystallize in the triclinic P1 space group, whereas W crystallizes with higher symmetry in the monoclinic C2/m space group. The crystal structure predicts that the three remaining carbonyl ligands reach into the voids of the hexagonal tiling. The hexagon is in chair conformation leading to <M–M–M angles approaching 90° with hexagonal pore channels of roughly 5.5–6.5 Å. The hexagon for W is nearly equilateral in nature compared to Mo, which exhibits unequal hexagon edges.

Fig 1: Single crystal structure of Cr, Mo, and W: (a) View of the hexagonal pore channels in W. (b) Stack of coordination layers in W. (c) Chair conformation of the hexagonal arrangement shown for W. The solvent molecules inside the pores and the disorder are not shown for clarity in (a–c). (d–f) Hexagonal fragments of Cr, Mo, and W together with the pyz molecule contained in the pores (not visible for W due to solvent mask, see methods). The positional disorder of the pyz molecules in W is also shown.

The typical IR absorption band related to M-CO stretching is explored for characterizing the complexes. A red shift of ~310 cm^-1 in the spectra of the average carbonyl stretching band was obtained, which is approximated as a ~25% decrease of the force constant associated with the C–O bond. The thermogravimetric analysis showed that the Mo complex has the highest thermal stability with an onset of degradation around 180°C, whereas Cr and W underwent significant mass loss from around 150°C and 130°C, respectively. A similar trend is observed for the stability of the complexes in atmospheric air.

These first examples of structurally characterized zero-valent MOFs with metal nodes derived from metal carbonyls could be attractive architectures for the exploration of catalytic applications as they facilitate the possibility for the non-destructive removal of pore-filling molecules.

For further details, please go to:

Zero-valent metals in metal–organic frameworks: fac-M(CO)3(pyrazine)3/2

Laura Voigt, Rene´ Wugt Larsen, Mariusz Kubus and Kasper S. Pedersen*

Chem. Commun., 2021, 57, 3861

About the writer:

Damayanti Bagchi, PhD, is a postdoctoral researcher in Irene Chen’s lab at University of California, Los Angeles, United States. She has obtained her PhD in Physical Chemistry from Satyendra Nath Bose National Centre for Basic Sciences, India. Her research is focused on spectroscopic studies of nano-bio interface and phage therapy. She is interested in science communication and science policy-diplomacy. She enjoys travelling and experimenting with various cuisines!

You can find her on Twitter @DamayantiBagchi