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Special Issue "Signaling Molecules: Hydrogen Sulfide and Polysulfide"

A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Chemical Biology".

Deadline for manuscript submissions: 15 May 2019

Special Issue Editor

Guest Editor
Prof. Dr. Claus Jacob

Division of Bioorganic Chemistry, School of Pharmacy, Saarland University, D-66123 Saarbruecken, Germany
Website | E-Mail
Phone: 00496813023129
Interests: bioethics; bioorganic chemistry; epistemology; dissemination; pharmasophy; theory of science

Special Issue Information

Dear Colleagues,

During the last decade, various inorganic polysulfides (H2Sx, x ≥ 2) have emerged as potential and potent cellular signalling molecules. Numerous (bio)chemical reactions and biological activities have been ascribed to these astonishingly simple reactive sulfur species (RSS), ranging from chemopreventive and antioxidant properties to intricate posttranslational protein modifications and redox signalling. There is even some evidence that such molecules may modulate the intracellular redox status and induce apoptosis in selected target cells.

Indeed, whilst inorganic polysulfides are—chemically speaking—among the most “primitive” molecules, i.e. sulfur chains composed exclusively of sulfur and some hydrogen, their reactivity resembles the one of H2S on the one side and that of organic polysulfides/polysulfanes (RSxR, x > 2), such as the diallylsulfanes from garlic, on the other. An unassuming molecule such as S22-, for instance, is a fine reducing agent and a ligand for metal ions, just like H2S; still, it is also an oxidant able to modify cysteine residues via S-thiolation. There has even been some suspicion that the biochemistry assigned traditionally to H2S in part may be one of these polysulfides.

Undoubtedly, the biological activities of polysulfides are highly complicated, and we are just at the beginning of understanding some of them. Since these RSS are intrinsically difficult to detect, especially in complex biological environments, such investigations are inherently tedious and often marred by artefacts. Still, there has been notable progress in the analytics as well as the redox biology of H2Sx over the years, and it is now a good time to take stock of the present knowledge and look at future developments in this emerging field. As part of this Special Issue, chemistry and biochemistry will join up to solve some of the challenges of sulfur redox biology, from the appearance, activities, and possible applications of H2S and H2Sx to the interactions of such species with thiols, disulfides, selenium, cysteine proteins, and redox signalling via the cellular thiolstat.

Prof. Dr. Claus Jacob
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All papers will be peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. Molecules is an international peer-reviewed open access bimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 1800 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.


  • cellular thiolstat
  • cysteine
  • polysulfides
  • Reactive Sulfur Species
  • redox modulation
  • signaling

Published Papers

This special issue is now open for submission, see below for planned papers.

Planned Papers

The below list represents only planned manuscripts. Some of these manuscripts have not been received by the Editorial Office yet. Papers submitted to MDPI journals are subject to peer-review.

Type: Review
Title: From Elemental Sulfur to Hydrogen Sulfide in Agricultural Soils and Plants.
Author: Adalberto Benavides-Mendoza
Affiliation: Departamento de Horticultura, Universidad Autónoma Agraria Antonio Narro, Saltillo 25315, Coahuila, Mexico;
Abstract: Sulfur is an essential element in determining the productivity and quality of agricultural products. It is also an element associated with tolerance to biotic and abiotic stress in plants. In agricultural practice, sulfur has broad use in the form of sulfate fertilizer and, to a lesser extent, as sulfite biostimulant. When used in the form of bulk elemental sulfur, or micro-or nano-sulfur, applied both to the soil and to the canopy, the element undergoes a series of changes in the oxidation state, produced by various intermediaries (S+2 --> S+5) that act apparently as biostimulants and promoters of stress tolerance. The final result is sulfate S+6 which is the source of sulfur that all soil organisms assimilate and that plants absorb by the radical cells. The changes in the oxidation states of sulfur S0 to S6 depends on the action of specific groups of edaphic bacteria. In plant cells, S+6 sulfate is reduced to S-2 and incorporated into biological molecules. S-2 is also absorbed by stomata from H2S, COS, and other atmospheric sources. S-2 is the precursor of polysulfides and H2S whose action as cell signaling and biostimulants has been described in plants. S-2 is also the basis of essential biological molecules in signaling, metabolism and stress tolerance such as SAM, glutathione, and phytochelatins. The present review describes the dynamics of sulfur in soil and plants, considering as the starting point the elemental sulfur and as a final point, the sulfur accumulated as S-2 in the biological structures. The factors that modify the behavior of the different components of the sulfur cycle in the soil-plant-atmosphere system are described and how these influence the productivity, quality and stress tolerance of crops. The internal and external factors that influence the cellular production of S-2 and polysulfides vs. other S species are also described. The impact of elemental sulfur is compared with that of sulfates, in a context of proper soil management. The conclusion is that the use of elemental sulfur is recommended over that of sulfates, since it is beneficial for the soil microbiome, for the productivity and nutritional quality of the crops, also allowing to increase the tolerance of plants to environmental stresses.

Title: H2S vs polysulfides interacting with doxycyclines induce DNA cleavage and scavenge •cPTIO radical
Karol Ondrias
Institute of Clinical and Translational Research, Biomedical Research Center, Slovak Academy of Sciences, Bratislava, Slovak Republic; [email protected]
Intermediates and/or products of H2S interaction with tetracycline antibiotics, doxycycline, oxytetracycline and tetracycline have the property to cleave plasmid DNA and reduce •cPTIO radical. The effects of H2S are compared with polysuldide HS4. The results may imply an involvement of H2S/tetracyclines interaction in scavenging of free radicals and toxicity.

Matthew Whiteman
University of Exeter Medical School, St. Luke's Campus, Magdelen Road, Exeter, UK; [email protected]
The development of vascular complications associated with diabetes and other cardiovascular disorders are initiated, at least in part, by mitochondrial dysfunction, mitochondrial reactive oxygen species (‘ROS’) and decreased bioavailability and/or synthesis of vasoprotective mediators such as hydrogen sulfide (H2S). We have previously shown that triphenylphosphonium-based mitochondria-targeted H2S delivery molecules such as AP39 reversed hyperglycaemia-induced endothelial dysfunction. In this current study we evaluated the cellular effects of a potential carbonyl metabolite of AP39 (RT01). The addition of RT01 to murine microvascular endothelial (b.End3) cells mitochondrial H2S accumulation and a concentration- and time-dependent increase in H2S generation but at a slower rate and for a shorter period of time than AP39. RT01 was well tolerated by b.End3 cells (TC50 = 11.1 µM c.f. AP39 = 8.3 µM) and reversed hyperglycaemia-induced hyperpolarisation of the mitochondrial membrane (3–300 nM) and mitochondrial ‘ROS’ production (3–300 nM) in a concentration-dependent manner (3–300 nM). These data further suggest that targeting H2S (and/or its derivatives or products e.g. persulfides or perthiols) to mitochondria may represent a novel approach to disease treatment associated with mitochondrial dysfunction.

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