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A highly sensitive and specific luminescent MOF determines nitric oxide production and quantifies hydrogen sulfide-mediated inhibition of nitric oxide in living cells

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Abstract

The synthesis of a novel carboxylate-type organic linker-based luminescent MOF (Zn(H2L) (L1)) (named PUC2) (H2L = 2-aminoterephtalic acid, L1 = 1-(3-aminopropyl) imidazole) is reported by the solvothermal method and comprehensively characterized using single-crystal XRD, PXRD, FTIR, TGA, XPS, FESEM, HRTEM, and BET. PUC2 selectively reacts with nitric oxide (NO) with a detection limit of 0.08 µM, and a quenching constant (0.5 × 104 M−1) indicating a strong interaction with NO. PUC2 sensitivity remains unaffected by cellular proteins or biologically relevant metals (Cu2+/ Fe3+/Mg2+/ Na+/K+/Zn2+), RNS/ROS, or H2S to score NO in living cells. Lastly, we used PUC2 to demonstrate that H2S inhibition increases NO production by ~ 14–30% in various living cells while exogenous H2S suppresses NO production, indicating that the modulation of cellular NO production by H2S is rather generic and not restricted to a particular cell type. In conclusion, PUC2 can successfully detect NO production in living cells and environmental samples with considerable potential for its application in improving the understanding of the role of NO in biological samples and study the inter-relationship between NO and H2S.

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Data availability

CCDC 1,993,716 contains the supplementary crystallographic data for this paper. Data can be requested via www.ccdc.cam.ac.uk/data_request/cif, or by emailing data_request@ccdc.cam.ac.uk.

Abbreviations

XRD:

X-ray powder diffraction

PXRD:

Powder X-ray diffraction

FTIR:

Fourier-transform infrared spectroscopy

TGA:

Thermogravimetric analysis

XPS:

X-ray photoelectron spectroscopy

FESEM:

Field emission scanning electron microscopy

HRTEM:

High-resolution transmission electron microscopy

BET:

Brunauer-Emmett-Teller

CBS:

Cystathionine beta-synthase

CSE:

Cystathionine gamma-lyase

References

  1. Lee SR, Nilius B, Han J (2018) Gaseous signaling molecules in cardiovascular function: from mechanisms to clinical translation. Rev Physiol Biochem Pharmacol 174:81–156. https://doi.org/10.1007/112_2017_7

    Article  CAS  PubMed  Google Scholar 

  2. Yang C-S, Yuk J-M, Jo E-K (2009) The role of nitric oxide in mycobacterial infections. Immune Netw 9:46. https://doi.org/10.4110/in.2009.9.2.46

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Möller MN, Rios N, Trujillo M et al (2019) Detection and quantification of nitric oxide-derived oxidants in biological systems. J Biol Chem 294:14776–14802. https://doi.org/10.1074/jbc.REV119.006136

    Article  PubMed  PubMed Central  Google Scholar 

  4. Gautam K, Negi S, Saini V (2021) Targeting endogenous gaseous signaling molecules as novel host-directed therapies against tuberculosis infection. Free Radic Res 55:903–918. https://doi.org/10.1080/10715762.2021.1892091

    Article  CAS  Google Scholar 

  5. Cirino G, Vellecco V, Bucci M (2017) Nitric oxide and hydrogen sulfide: the gasotransmitter paradigm of the vascular system. Br J Pharmacol 174:4021–4031. https://doi.org/10.1111/bph.13815

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Saini V, Chinta KC, Reddy VP et al (2020) Hydrogen sulfide stimulates Mycobacterium tuberculosis respiration, growth and pathogenesis. Nat Commun 11:1–17. https://doi.org/10.1038/s41467-019-14132-y

    Article  CAS  Google Scholar 

  7. Manisalidis I, Stavropoulou E, Stavropoulos A, Bezirtzoglou E (2020) Environmental and health impacts of air pollution: a review. Front Public Heal 8:1–13. https://doi.org/10.3389/fpubh.2020.00014

    Article  Google Scholar 

  8. Kumar A, Sahoo SC, Mehta SK et al (2022) A luminescent Zn-MOF for the detection of explosives and development of fingerprints. Anal Methods 14:700–707. https://doi.org/10.1039/D1AY01977E

    Article  CAS  PubMed  Google Scholar 

  9. Kirandeep, Kumar A, Sharma A et al (2021) Metal organic framework as “turn-on” fluorescent sensor for Zr(IV) ions and selective adsorbent for organic dyes. Microchem J 171:106824. https://doi.org/10.1016/j.microc.2021.106824

    Article  CAS  Google Scholar 

  10. Arya K, Kumar A, Sharma A et al (2022) A hybrid nanocomposite of coordination polymer and rGO for photocatalytic degradation of Safranin-O dye under visible light irradiation. Top Catal. https://doi.org/10.1007/s11244-022-01701-7

    Article  Google Scholar 

  11. Huo Y, Miao J, Han L et al (2017) Selective and sensitive visualization of endogenous nitric oxide in living cells and animals by a Si-rhodamine deoxylactam-based near-infrared fluorescent probe. Chem Sci 10:6857–6864. https://doi.org/10.1039/C7SC02608K

    Article  Google Scholar 

  12. Lv X, Wang Y, Zhang S et al (2014) A specific fluorescent probe for NO based on a new NO-binding group. Chem Commun 50:7499–7502. https://doi.org/10.1039/c4cc03540b

    Article  CAS  Google Scholar 

  13. Alizadeh N, Salimi A, Sham TK (2021) CuO/Cu-MOF nanocomposite for highly sensitive detection of nitric oxide released from living cells using an electrochemical microfluidic device. Microchim Acta 188:1–11. https://doi.org/10.1007/s00604-021-04891-1

    Article  CAS  Google Scholar 

  14. Ostovan A, Arabi M, Wang Y et al (2022) Greenificated molecularly imprinted materials for advanced applications. Adv Mater 34:2203154. https://doi.org/10.1002/adma.202203154

    Article  CAS  Google Scholar 

  15. Arabi M, Ostovan A, Li J et al (2021) Molecular imprinting: green perspectives and strategies. Adv Mater 33:1–33. https://doi.org/10.1002/adma.202100543

    Article  CAS  Google Scholar 

  16. Kolluru GK, Shen X, Kevil CG (2013) A tale of two gases: NO and H2S, foes or friends for life? Redox Biol 1:313–318. https://doi.org/10.1016/j.redox.2013.05.001

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Desai AV, Samanta P, Manna B, Ghosh SK (2015) Aqueous phase nitric oxide detection by an amine-decorated metal - organic framework. Chem Commun 51:6111–6114. https://doi.org/10.1039/c5cc00773a

    Article  CAS  Google Scholar 

  18. Yu H, Xiao Y, Jin L (2012) A lysosome-targetable and two-photon fluorescent probe for monitoring endogenous and exogenous nitric oxide in living cells. J Am Chem Soc 134:17486–17489. https://doi.org/10.1021/ja308967u

    Article  CAS  PubMed  Google Scholar 

  19. Wu P, Wang J, He C et al (2012) Luminescent metal-organic frameworks for selectively sensing nitric oxide in an aqueous solution and in living cells. Adv Funct Mater 22:1698–1703. https://doi.org/10.1002/adfm.201102157

    Article  CAS  Google Scholar 

  20. Oh GS, Pae HO, Lee BS et al (2006) Hydrogen sulfide inhibits nitric oxide production and nuclear factor-κB via heme oxygenase-1 expression in RAW264.7 macrophages stimulated with lipopolysaccharide. Free Radic Biol Med 41:106–119. https://doi.org/10.1016/j.freeradbiomed.2006.03.021

    Article  CAS  PubMed  Google Scholar 

  21. Uppu RM (2006) Synthesis of peroxynitrite using isoamyl nitrite and hydrogen peroxide in a homogeneous solvent system. Anal Biochem 354:165–168. https://doi.org/10.1016/j.ab.2005.11.003

    Article  CAS  PubMed  Google Scholar 

  22. Richa KN, Negi S et al (2021) Synthesis, characterization and utility of a series of novel copper( ii ) complexes as excellent surface disinfectants against nosocomial infections. Dalt Trans. https://doi.org/10.1039/d1dt00199j

    Article  Google Scholar 

  23. Kumar P, Saini K, Saini V et al (2021) Oxalate alters cellular bioenergetics, redox homeostasis, antibacterial response, and immune response in macrophages. Front Immunol 12:694865. https://www.frontiersin.org/articles/10.3389/fimmu.2021.694865

  24. Starr T, Bauler TJ, Malik-Kale P, Steele-Mortimer O (2018) The phorbol 12-myristate-13-acetate differentiation protocol is critical to the interaction of THP-1 macrophages with Salmonella Typhimurium. PLoS One 13:e0193601. https://doi.org/10.1371/journal.pone.0193601

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Saini V, Sikri K, Batra SD et al (2020) Development of a highly effective low-cost vaporized hydrogen peroxide-based method for disinfection of personal protective equipment for their selective reuse during pandemics. Gut Pathog 12:1–11. https://doi.org/10.1186/s13099-020-00367-4

    Article  CAS  Google Scholar 

  26. Saini V, Cumming BM, Guidry L et al (2016) Ergothioneine maintains redox and bioenergetic homeostasis essential for drug susceptibility and virulence of mycobacterium tuberculosis. Cell Rep 14:572–585. https://doi.org/10.1016/j.celrep.2015.12.056

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Li L, Whiteman M, Guan YY et al (2008) Characterization of a novel, water-soluble hydrogen sulfide-releasing molecule (GYY4137): new insights into the biology of hydrogen sulfide. Circ 117:2351–2360. https://doi.org/10.1161/CIRCULATIONAHA.107.753467

    Article  CAS  Google Scholar 

  28. Dong S, Hu J, Zhang X, Zheng M (2018) A bifunctional Zn(II)-MOF as recyclable luminescent sensor for detecting TNT and Fe 3+ with high selectivity and sensitivity. Inorg Chem Commun 97:180–186. https://doi.org/10.1016/j.inoche.2018.09.039

    Article  CAS  Google Scholar 

  29. Ghosh TK, Jana S, Ghosh A (2018) Exploitation of the flexidentate nature of a ligand to synthesize Zn(II) complexes of diverse nuclearity and their use in solid-state naked eye detection and aqueous phase sensing of 2,4,6-trinitrophenol. Inorg Chem 57:15216–15228. https://doi.org/10.1021/acs.inorgchem.8b02497

    Article  CAS  PubMed  Google Scholar 

  30. Xu W, Chen H, Xia Z et al (2019) A robust TbIII-MOF for ultrasensitive detection of trinitrophenol: matched channel dimensions and strong host-guest interactions. Inorg Chem 58:8198–8207. https://doi.org/10.1021/acs.inorgchem.9b01008

    Article  CAS  PubMed  Google Scholar 

  31. Buragohain A, Yousufuddin M, Sarma M, Biswas S (2016) 3D Luminescent amide-functionalized cadmium tetrazolate framework for selective detection of 2,4,6-trinitrophenol. Cryst Growth Des 16:842–851. https://doi.org/10.1021/acs.cgd.5b01427

    Article  CAS  Google Scholar 

  32. Yang SH, Park SK, Kang YC (2021) MOF-derived CoSe2@N-doped carbon matrix confined in hollow mesoporous carbon nanospheres as high-performance anodes for potassium-ion batteries. Nano-Micro Lett 13:1–15. https://doi.org/10.1007/s40820-020-00539-6

    Article  CAS  Google Scholar 

  33. Kaur M, Mehta SK, Kansal SK (2020) Amine-functionalized titanium metal-organic framework (NH2-MIL-125(Ti)): a novel fluorescent sensor for the highly selective sensing of copper ions. Mater Chem Phys 254:123539. https://doi.org/10.1016/j.matchemphys.2020.123539

  34. Zhu S, Yin H, Wang Y et al (2020) Heteroatomic interface engineering of MOF-derived metal-embedded P- and N-Codoped Zn node porous polyhedral carbon with enhanced sodium-ion storage. ACS Appl Energy Mater 3:8892–8902. https://doi.org/10.1021/acsaem.0c01365

    Article  CAS  Google Scholar 

  35. Xie S, Qin Q, Liu H et al (2020) MOF-74-M (M = Mn Co, Ni, Zn, MnCo, MnNI, and MnZn) for low-temperature NH3-SCR and in situ Drifts study reaction mechanism. ACS Appl Mater Interfaces 12:48476–48485. https://doi.org/10.1021/acsami.0c11035

    Article  CAS  PubMed  Google Scholar 

  36. Ma SF, Wang QH, Liu FT et al (2016) Dihydropyridine-based fluorescence probe for nitric oxide. RSC Adv 6:85698–85703. https://doi.org/10.1039/c6ra16713f

    Article  CAS  Google Scholar 

  37. Peng B, Chen W, Liu C et al (2014) Fluorescent probes based on nucleophilic substitution-cyclization for hydrogen sulfide detection and bioimaging. Chem - A Eur J 20:1010–1016. https://doi.org/10.1002/chem.201303757

    Article  CAS  Google Scholar 

  38. Shang L, Nienhaus K, Nienhaus GU (2014) Engineered nanoparticles interacting with cells: Size matters. J Nanobiotechnology 12:1–11. https://doi.org/10.1186/1477-3155-12-5

    Article  CAS  Google Scholar 

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Acknowledgements

DST and GOI are acknowledged for PURSE Grant (II) and FIST(II) (SR/FISTIICSII-036/2015(c) and (G) dated 02.06.2016) for single crystal facility at the Department of Chemistry, Punjab University, Chandigarh. Ajay Kumar, Sheetal Negi, and Dr Vishal Mutreja acknowledge the CSIR-SRF program, and SERB National Post-Doctoral Fellowship, Govt of India.

Funding

This work is supported primarily through Har Gobind Khorana Innovative Young Biotechnologist Award (BT/11/IYBA/2018/01) to VS; and in part by DST-SERB (CRG/2018/004510), Life Science Research Board, DRDO, India (LSRB-375/SH&DD/2020) and Consortium for One Health to address Zoonotic and Transboundary Diseases in India (BT/PR39032/ADV/90/285/2020) to VS.

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Authors and Affiliations

Authors

Contributions

Experimentation and chemistry: AK. Biological and in vitro cellular studies: SN. Animal cell isolation studies: SN and TC. Data analysis: AK, SN, TC, SS, SCS, VM, AS, SKM, RK, and VS. Writing and editing: AK, SN, RK, and VS. Conceptualization: RK and VS. Overall supervision: RK and VS. Funding: VS.

Corresponding authors

Correspondence to Surinder K. Mehta, Ramesh Kataria or Vikram Saini.

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The study is approved by the Institutional Ethical Committee AIIMS New Delhi (IECPG/708/29.09.20220, Institutional Animal Ethics Committee(IAEC) and Institutional Biosafety Committee (IBSC), AIIMS New Delhi (IBSC0521_VS).

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Kumar, A., Negi, S., Choudhury, T. et al. A highly sensitive and specific luminescent MOF determines nitric oxide production and quantifies hydrogen sulfide-mediated inhibition of nitric oxide in living cells. Microchim Acta 190, 127 (2023). https://doi.org/10.1007/s00604-023-05660-y

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