rose bengal
{{Short description|Tetrachloro-tetraiodo-fluorescein used as stain}}
{{cs1 config|name-list-style=vanc}}
{{chembox
| Verifiedfields = changed
| Watchedfields = changed
| verifiedrevid = 417216360
| ImageFile = rosebengalskeletal.png
| ImageSize =
| PIN = 4,5,6,7-Tetrachloro-3′,6′-dihydroxy-2′,4′,5′,7′-tetraiodo-3H-spiro[
| OtherNames = * C.I. 45440
- C.I. Acid Red 94
|Section1={{Chembox Identifiers
| CASNo_Ref = {{cascite|correct|CAS}}
| CASNo = 4159-77-7
| PubChem = 69439
| ChemSpiderID = 62647
| ChEMBL_Ref = {{ebicite|correct|EBI}}
| ChEMBL = 1160160
| EC_number = 223-993-4
| UNII = BIU7Q7W2SH
| StdInChI=1S/C20H4Cl4I4O5/c21-9-7-8(10(22)12(24)11(9)23)20(33-19(7)31)3-1-5(25)15(29)13(27)17(3)32-18-4(20)2-6(26)16(30)14(18)28/h1-2,29-30H
| StdInChIKey = IICCLYANAQEHCI-UHFFFAOYSA-N
| SMILES = O=C(O1)C2=C(C(Cl)=C(Cl)C(Cl)=C2Cl)C31C4=C(C(I)=C(O)C(I)=C4)OC5=C(I)C(O)=C(I)C=C53
}}
|Section2={{Chembox Properties
| Formula =
| C=20 | H=4 | Cl=4 | I=4 | O=5
| MolarMass = 973.67 g/mol
1,017.65 g/mol (sodium salt)
| Appearance =
| Density =
| MeltingPt =
| BoilingPt =
| Solubility = }}
|Section6={{Chembox Pharmacology
| ATCCode_prefix = S01
| ATCCode_suffix = JA02
}}
|Section7={{Chembox Hazards
| GHSPictograms = {{GHS07}}
| GHSSignalWord = Warning
| HPhrases = {{H-phrases|315|319|335}}
| PPhrases = {{P-phrases|261|264|271|280|302+352|304+340|305+351+338|312|321|332+313|337+313|362|403+233|405|501}}
| MainHazards =
| FlashPt =
| AutoignitionPt = }}
}}
Rose bengal (4,5,6,7-tetrachloro-2',4',5',7'-tetraiodofluorescein) is a stain. Rose bengal belongs to the class of organic compounds called xanthenes.{{cite web |title=Rose Bengal Compound Summary |url=https://pubchem.ncbi.nlm.nih.gov/compound/Rose-bengal |website=PubChem}} Its sodium salt is commonly used in eye drops to stain damaged conjunctival and corneal cells and thereby identify damage to the eye. The stain is also used in the preparation of Foraminifera for microscopic analysis, allowing the distinction between forms that were alive or dead at the time of collection.
A form of rose bengal is also being studied as a treatment for certain cancers and skin conditions. The cancer formulation of the drug, known as PV-10, is currently undergoing clinical trials for melanoma, breast cancer. and [https://clinicaltrials.gov/ct2/show/NCT02693067 neuroendocrine tumors]. The company also has formulated a drug based on rose bengal for the treatment of eczema and psoriasis; this drug, PV-10, is currently in clinical trials as well.
History and etymology
Rose bengal was originally prepared in 1882 by Swiss chemist Robert Ghnem, as an analogue of fluorescein.{{cite journal|last=Alexander|first=Walter|title=American Society of Clinical Oncology, 2010 Annual Meeting and Rose Bengal: From a Wool Dye to a Cancer Therapy|journal=Pharmacy and Therapeutics|year=2010|volume=35|issue=8|pages=469–474|pmc=2935646|pmid=20844697}} Rudolf Nietzki at the University of Basel identified the principal constituents of rose bengal as iodine derivatives of di- and tetra-chlorofluorescein.{{cite web |last1=Orellana |first1=Claudia |title=Rose Bengal The pink eye stain that might be a cancer treatment |url=http://www.chm.bris.ac.uk/motm/rose-bengal/rose-bengalh.htm}} The compound was originally used as a wool dye.{{cite web |last1=Orellana |first1=Claudia |title=Rose Bengal--the Pink Eye Stain that might be a Cancer Treatment |url=http://www.chm.bris.ac.uk/motm/rose-bengal/rose-bengalh.htm}} Its name derives from rose (flower) and Bengal (region); it is printed as rose bengal or Rose Bengal in the scientific literature.{{cite book|author=Senning, Alexander |title=Elsevier's Dictionary of Chemoetymology: The Whys and Whences of Chemical Nomenclature and Terminology|url=https://books.google.com/books?id=Fl4sdCYrq3cC&pg=PA344|date=2006|publisher=Elsevier|isbn=978-0-08-048881-3|page=344}}
Chemical applications
Image:Spinoloricus.png from Loricifera stained with rose bengal.]]
Despite its complicated photochemistry involving several species,{{Cite journal|last1=Ludvíková|first1=Lucie|last2=Friš|first2=Pavel|last3=Heger|first3=Dominik|last4=Šebej|first4=Peter|last5=Wirz|first5=Jakob|last6=Klán|first6=Petr|date=2016|title=Photochemistry of rose bengal in water and acetonitrile: a comprehensive kinetic analysis|journal=Physical Chemistry Chemical Physics|language=en|volume=18|issue=24|pages=16266–16273|doi=10.1039/C6CP01710J|pmid=27253480|bibcode=2016PCCP...1816266L|issn=1463-9076}} rose bengal is also used in synthetic chemistry as a visible light photoredox catalyst{{Cite journal |last1=Romero |first1=Nathan A. |last2=Nicewicz |first2=David A. |date=2016-09-14 |title=Organic Photoredox Catalysis |url=https://pubs.acs.org/doi/10.1021/acs.chemrev.6b00057 |journal=Chemical Reviews |language=en |volume=116 |issue=17 |pages=10075–10166 |doi=10.1021/acs.chemrev.6b00057 |pmid=27285582 |issn=0009-2665}} and to generate singlet oxygen from triplet oxygen. The singlet oxygen can then undergo a variety of useful reactions, particularly [2 + 2] cycloadditions with alkenes and similar systems.
=Derivatives and salts=
Rose bengal can be used to form many derivatives that have important medical functions. One such derivative was created so to be sonosensitive but photoinsensitive, so that with a high intensity focused ultrasound, it could be used in the treatment of cancer. The derivative was formed by amidation of rose bengal, which turned off the fluorescent and photosensitive properties of rose bengal, leading to a usable compound, named in the study as RB2.{{cite journal|last=Kim|first=Y |author2=Valentina Rubio |author3=Jianjun Qi |author4=Rongmin Xia |author5=Zheng-Zheng Shi |author6=Leif Peterson |author7=Ching-Hsuan Tung |author8=Brian E. O'Neill|title=Cancer treatment using an optically inert rose bengal derivative combined with pulsed focused ultrasound|journal=AIP Conference Proceedings|year=2012|volume=1481|issue=1 |page=175|doi=10.1063/1.4757330|bibcode=2012AIPC.1481..175K }} Published as {{cite journal|pmid=21871506|pmc=3230682|doi=10.1016/j.jconrel.2011.08.016 | volume=156|issue=3|title=Cancer treatment using an optically inert Rose Bengal derivative combined with pulsed focused ultrasound|year=2011|journal=J Control Release|pages=315–22 | last1 = Kim | first1 = YS | last2 = Rubio | first2 = V | last3 = Qi | first3 = J | last4 = Xia | first4 = R | last5 = Shi | first5 = ZZ | last6 = Peterson | first6 = L | last7 = Tung | first7 = CH | last8 = O'Neill | first8 = BE}}
File:Rose_bengal_sodium_salt_structure.png
Salts of rose bengal include C20H2Cl4I4Na2O5 (CAS 632-69-9). This sodium salt is a dye, which has its own unique properties and uses.{{cite web|title=Rose Bengal Sodium Salt|url=http://www.sigmaaldrich.com/catalog/product/sigma/r3877?lang=en®ion=US|work=Sigma-Aldrich|publisher=Sigma Aldrich Co.|access-date=12 November 2013}}
Biological applications
File:Rose Bengal Deneyi öncesi.jpg
PV-10 (an injectable form of rose bengal) was found to cause an observable response in 60% of tumors treated, according to researchers in a phase II melanoma study. Locoregional disease control was observed in 75% of patients. Also confirmed was a "bystander effect", previously observed in the phase I trial, whereby untreated lesions responded to treatment as well, potentially due to immune system response. These data were based on the interim results (in 2009) of the first 40 patients treated in an 80-patient study.[http://www.medicalnewstoday.com/articles/153024.php Metastatic Melanoma PV-10 Trial Results Encouraging Says Drug Company], Medical News Today, 9 June 2009{{update after|2011}} {{as of|2016|4}} a phase-3 study of PV-10 as a single agent therapy for patients with locally advanced cutaneous melanoma (Clinical Trials ID NCT02288897) is enrolling patients.[http://www.businesswire.com/news/home/20160422005164/en/Provectus-Biopharmaceuticals-Reports-Data-PV-10-Combination-Therapy Provectus Biopharmaceuticals Reports Data On PV-10 in Combination Therapy and T Cell Mediated Immunity Presented at American Association for Cancer Research (AACR) Annual Meeting 2016. April 2016]
Rose bengal has been shown to not just prevent the growth and spread of ovarian cancer, but also to cause apoptotic cell death of the cancer cells. This has been proven in vitro, in order to prove that rose bengal is still a possible option in the treatment of cancer, and further research should be done.{{cite journal|last=Koevary|first=S|title=Selective toxicity of rose bengal to ovarian cancer cells in vitro|journal=International Journal of Physiology, Pathophysiology and Pharmacology|year=2012|volume=4|issue=2|pages=99–107|pmid=22837809|pmc=3403562}}
Rose bengal has been used to treat colon cancer. In one such study,{{cite journal |last1=Qin |first1=Jianzhong |title=Colon cancer cell treatment with rose bengal generates a protective immune response via immunogenic cell death |journal=Cell Death and Disease |date=2017 |volume=8 |issue=2 |page=e2584 |doi=10.1038/cddis.2016.473 |pmid=28151483 |pmc=5386459 |url=}} a protective immune response was generated from immunogenic cell death.
Rose bengal is also used in animal models of ischemic stroke (photothrombotic stroke models) in biomedical research. A bolus of the compound is injected into the venous system. Then the region of interest (e.g., the cerebral cortex) is exposed and illuminated by LASER light of 561 nm. A thrombus is formed in the illuminated blood vessels, causing a stroke in the dependent brain tissue.{{cite journal |vauthors=Salber D, etal | title = Differential uptake of [18F]FET and [3H]l-methionine in focal cortical ischemia | journal = Nuclear Medicine and Biology | volume = 33 | issue = 8 | pages =1029–1035 | doi = 10.1016/j.nucmedbio.2006.09.004 | pmid = 17127177 | year = 2006}}{{cite journal |vauthors=Watson BD, Dietrich WD, Busto R, Wachtel MS, Ginsberg MD | title = Induction of reproducible brain infarction by photochemically initiated thrombosis | journal = Ann Neurol | volume = 17 | pages = 497–504 | year = 1985 | doi = 10.1002/ana.410170513 | pmid = 4004172 | issue = 5| s2cid = 37827695 }}
Rose bengal has been used for 50 years to diagnose liver and eye cancer. Rose bengal dye is mixed with the homogenate of Brucella and pH of the solution is maintained at 3.8, and this dye is used to diagnose Brucellosis by agglutinating the suspected serum. Rose bengal is slightly irritating and toxic to the eye. It has also been used as an insecticide.{{cite journal | doi = 10.1603/0022-0493-93.3.662 | title = Insecticidal Activity of Photoactive Dyes to American and Migratory Grasshoppers (Orthoptera: Acrididae) | year = 2000 | last1 = Capinera | first1 = John L. | last2 = Squitier | first2 = Jason M. | journal = Journal of Economic Entomology | volume = 93 | issue = 3 | pages = 662–666 | pmid = 10902313| s2cid = 25514306 }}{{cite journal | doi = 10.1080/09583159830018 | title = Compatibility of Photoactive Dyes with Insect Biocontrol Agents | year = 1998 | last1 = Martin | first1 = Phyllis | last2 = Mischke | first2 = Sue | last3 = Schroder | first3 = Robert | journal = Biocontrol Science and Technology | volume = 8 | issue = 4 | pages = 501–508| bibcode = 1998BioST...8..501M | url = https://zenodo.org/record/1234461 }}
Rose bengal is able to stain cells whenever the surface epithelium is not being properly protected by the preocular tear film, because rose bengal has been proven to not be able to stain cells because of the protective functioning of these preocular tear films.{{cite journal|last=Feenstra|first=R|author2=Tseng, S |title=What is actually stained by rose bengal?|journal=Arch Ophthalmol|date=July 1992|volume=110|issue=7|pages=984–993|doi=10.1001/archopht.1992.01080190090035|pmid=1637285}} This is why rose bengal is often useful as a stain in diagnosing certain medical issues, such as conjunctival and lid disorders.{{cite journal|last=Yokoi|first=Norihiko|title=Vital staining for disorders of conjunctiva and lids|journal=Atarashii Ganka|year=2012|volume=29|pages=1599–1605}}
Rose bengal has been used for ocular surface staining to study the efficacy of punctal plugs in the treatment of keratoconjunctivitis sicca.{{cite journal |vauthors=Ervin AM, Wojciechowski R, Schein O |title= Punctal occlusion for dry eye syndrome |journal=Cochrane Database Syst Rev|volume=9 |pages= CD006775 |date=June 26, 2017 |issue= 6 |pmid= 28649802 |doi= 10.1002/14651858.CD006775.pub3 |pmc=5568656}}
Rose bengal is being researched as an agent in creating nano sutures.{{cite journal | doi = 10.1016/j.actbio.2008.06.007 | title = Effects of photochemical crosslinking on the microstructure of collagen and a feasibility study on controlled protein release | year = 2008 | last1 = Chan | first1 = B | last2 = Chan | first2 = O | last3 = So | first3 = K | journal = Acta Biomaterialia | volume = 4 | issue = 6 | pages = 1627–1636 | pmid = 18640085}} Wounds are painted on both sides with it and then illuminated with an intense light. This links the tiny collagen fibers together sealing the wound.{{cite journal | author = O’Neill A.C., Winograd J.M, Zeballos J.M., Johnson T.S., Randolph M.A., Bujold K.E., Kochevar I.E., Redmond R.W. | journal = Lasers in Surgery and Medicine | volume = 39 | pages = 716–722 | year = 2007 | doi = 10.1002/lsm.20548 | pmid = 17960755 | title = Microvascular anastomosis using a photochemical tissue bonding technique | issue = 9| s2cid = 46712914 }}{{cite journal |author1=Mulroy L. |author2=Kim J. |author3=Wu I. |author4=Scharper P. |author5=Melki S.A. |author6=Azar D.A. |author7=Redmond R.W. |author8=Kochevar I.E. | journal = Invest Ophthalmol Vis Sci | year = 2000 | volume = 41 | pages = 3335–3340 | pmid = 11006222 | title = Photochemical keratodesmos for repair of lamellar corneal incisions | issue = 11}}{{cite journal |author1=Proano C.E. |author2=Mulroy L. |author3=Erika Jones E. |author4=Azar D.A. |author5=Redmond R.W. |author6=Kochevar I.E. | journal = Invest Ophthalmol Vis Sci | year = 2004 | pages = 2177–2181|title=Characterization of paracellular penetration routes|pmid=9344340 | volume=38|issue=11 }} Healing is faster and the seal reduces chances of infection.[http://www.technologyreview.com/biomedicine/22088/?nlid=1767 Laser Show in the Surgical Suite], Technology Review, March/April 2009[http://www.technologyreview.com/video/?vid=246 Laser Show in the Surgical Suite], Technology Review, 02.11.2009
Rose bengal is used to suppress bacterial growth in several microbiological media, including Cooke's rose bengal agar.
Rose bengal has been used as a protoplasm stain to discriminate between living and dead micro-organisms, particularly Foraminifera, since the 1950s when Bill Walton developed the technique.{{cite journal | last1 = Walton | first1 = W | year = 1952 | title = Techniques for recognition of living foraminifera | journal = Contrib. Cushman Found. Foraminiferal Res. | volume = 3 | pages = 56–60 }}
Rose bengal acetate can act as a photosensitiser and may have potential in photodynamic therapy to treat some cancers.{{cite journal | pmid = 25140900 | doi=10.1371/journal.pone.0105778 | volume=9 | issue=8 | title=Rose Bengal acetate photodynamic therapy (RBAc-PDT) induces exposure and release of Damage-Associated Molecular Patterns (DAMPs) in human HeLa cells | pmc=4139382 | journal=PLOS ONE | pages=e105778 | last1 = Panzarini | first1 = E | last2 = Inguscio | first2 = V | last3 = Fimia | first3 = GM | last4 = Dini | first4 = L| year=2014 | bibcode=2014PLoSO...9j5778P | doi-access=free }}
References
{{Reflist|30em}}
External links
- {{MeshName|Rose+Bengal}}
- [http://omlc.ogi.edu/spectra/PhotochemCAD/html/rosebengal.html Absorption and extinction data ]
{{Glutamate metabolism and transport modulators}}
{{Monoamine reuptake inhibitors}}
{{DEFAULTSORT:Rose Bengal}}
Category:Chlorobenzene derivatives