Talk Session 2

Mycobacterium Tuberculosis Glycolipids Disorganize Host Cell Membranes and Rewire Membrane-Associated Functions During Infection

Microbial lipids play a critical role in the pathogenesis of infectious diseases. 1 Mycobacterium tuberculosis (Mtb)—causative agent of Tuberculosis—synthesizes chemically distinct glycolipids that are exposed on its outer membrane and interact with the membranes of host macrophages. 2-3 However, the effects of the structurally diverse Mtb glycolipids on the host cell membrane properties to fine-tune the host cellular response is unknown. In this work, we combined membrane biophysics, cell biology and molecular simulations to assess the effects of different Mtb lipids on cell membrane mechanics, lipid diffusion, and cytoskeleton of THP-1 macrophages. 4-6 We found that Mtb lipids are transferred to macrophage membranes in a lab infection model, followed by modulation of macrophage membrane biophysical properties, and actin cytoskeleton. Physicochemical assays with Mtb sulpholipid-1 analogs revealed insights into their structure-function relationships highlighting specific roles of lipid acyl chains and head group along with effects on membrane-associated autophagy and cytokine signaling. Collectively, our work emphasizes that Mtb can fine-tune its interactions with the host cells by modulating its surface lipid profile during infection. These observations provide a novel lipid-centric paradigm of Mtb pathogenesis that is amenable to pharmacological inhibition and could promote the development of robust biomarkers of Mtb infection and pathogenesis.

Self-Assembled Hybrid Micro Droplets

Nematic liquid crystal (NLCs) microdroplets in water are a new type of functional material and it has been significantly explored in the sensing applications due to its tunable optical properties, high surface area and portability.1 However, there are only a few examples are shown in literature for the biofunctionalization of LC droplets with proteins which is specific. In this talk, I will present our work on preparation of bioactive hybrid material from LC droplets and biomolecules. We have developed a novel and generic method to prepare protein sequestered 4-cyano-4-pentylbiphenyl (5CB) LC droplets based on uptake of surface-engineered protein-polymer surfactant (PS) bioconjugates.2 The modification of protein with PS was carried out at a near-native structure. Combined Polarizing Optical Microscopy (POM) and Fluorescence imaging studies of mixing 5CB LC droplets with Myoglobin-PS (Mb-PS) bioconjugates show uptake of protein to the interior of droplets without structural or functional degrades. On the other hand native myoglobin (nMb) protein with 5CB droplets results in aggregation and destabilization. Isothermal Titration Calorimetry (ITC) study confirms a strong and favorable interaction between Mb-PS and 5CB LC droplets, unlike nMb. Microstructure analysis of LC droplets sequestered with Mb-PS bioconjugates using small-angle X-ray scattering and FTIR imaging experiments reveals the co-existence of protein phase within the organic LC phase. An interesting outcome from the Molecular dynamic simulation study confirms strong interaction between PS and LC which is driven by the hydrophobic part of the polymer chain and hence amphiphilic nature of PS stabilizes bioconjugates in an LC phase. Our method opens a new pathway to prepare the multifunctional material of LC and biomolecules that will find potential biosensing applications.

A Unique Fe(II)-S • Complex: Synthesis, Structure, Spectroscopy and Reactivity

In literature Non-heme Fe(IV)=O model systems, their spectroscopic properties and reactivity have been explored in detail. However, literature about Fe(III)-oxo compounds is scant, although they are important intermediates in iron-catalyzed oxidation reactions. The iron-sulfur systems have not found much attention although sulfido transition metal complexes are of biological importance for enzymatic and industrial hydride-sulfurization. Here we report a unique Fe(II)-S • complex of ligand L (Figure 1), its structural and electronic properties and reactivity. In solution, the triflate salt of the Iron(II) complex of ligand L is transformed quantitatively to the corresponding Fe(II)-S • complex and this Fe(II)-S • species thoroughly characterized by various spectroscopic techniques i.e., crystal structure, Mӧssbauer, EPR and further supported by DFT calculations. Electronic structure of complex 1a upon comparison to its analogue Fe-aqua complex i.e., complex 2 revealed that in case of complex 2, water molecule is attached to Fe-centre instead of sulfido moiety. The reactivity of the Fe II -S • complex was tested with tricyclohexylphosphine and yielded selectively the novel diphosphine product Cy 3 PSPCy 3 , characterized by 31 P-NMR and UPLC-MS.

Cascade reaction of curcuminoids with Morita-Baylis-Hillman bromides of nitroalkenes for the synthesis of 3,4-dihydro-2H-pyrans

Curcumin is the active phytochemical found in turmeric Curcuma longa.1 It is used as a food additive and curry spice in India and other eastern countries, mainly for its flavor and color profile. In ancient times, it was also used in ayurvedic medicines for the treatment of a variety of health conditions such as diabetic wounds, jaundice, skin burns, skin allergies, rheumatoid arthritis, respiratory illness, etc. Recently, many reports appeared in the literature that described the biological activities of curcumin, such as anti-oxidant, anticancer, anti-inflammatory, antimetastatic, anti-HIV protease and anti-Alzheimer’s.2 It is also found that different analogs of curcumin possess a variety of biological activities, and many of these synthetic compounds were more active than the naturally occurring curcumin.3 Hence, development of methodologies for the synthesis of differently substituted molecules from curcuminoids is gaining a great deal of interest.

Diverse reactivity exhibited by conjugated nitroalkenes and their derivatives was well explored in our laboratory for the synthesis of various carbocycles and heterocycles such as imidazoles, imidazopyridines, pyridopyrimidines, pyrroles, furans, pyrans, etc.4 Herein, we describe the stereo- and regioselective synthesis of nitro substituted 3,4-dihydro-2H-pyrans via a cascade reaction of Morita-Baylis-Hillman bromides of nitroalkenes with various curcuminoids under mild reaction conditions