Proflavin

Proflavine — see Acridine, 3,6-diamino-Progesterone, 11 of-hydroxy-racemic... 

Acriflavine [8048-52-0] M 196.2, pK >12. Treated twice with freshly ppted AgOH to remove proflavine, then recrystd from absolute methanol [Wen and Hsu J Phys Chem 66 1353 1962]. 

Acriflavin Mixture (Euflavin, 3,6-diamino-lO-metbylacridiniuni chloride) [8063-24-9] M 259.7, m 179-181 . Purified by dissolving in 50 parts of H2O, shake with a small excess of freshly ppted and washed Ag20. The mixture is set aside overnight at 0 and filtered. The cake is not washed. The pH of the filtrate is adjusted to 7.0 with HCl and evaporated to dryness. The residue is then crystd twice from MeOH, twice from H2O and dried at 120 X ,ax at 452nm has a loge value of 4.67. It is a red powder which readily absorbs H2O. The solubility is increased in the presence of proflavin. The dihydrochloride is a deep red crystn powder. It is available as a mixture of 3,6-diaminoacridinium chloride (35%) and its 10-metho-chloride (65%). [see Albert, The Acridines Arnold Press p. 346 1966 Chem Ber 45 1787 1912]. 

Diaminoacridine sulfate (proflavin sulfate) [1811-28-5] M 516.6, m >300°(dec), Xmax 456nm. An aqueous soln, after treatment with charcoal, was concentrated, chilled overnight, filtered and the ppte was rinsed with a little diethyl ether. The ppte was dried in air, then overnight in a vacuum oven at 70°. 

Proclavine (3,6-diaminoacridine) [92-62-6] M 209.2, m 284-286 , pK 9.60. Crystd from aqueous MeOH. For proflavin see 3,6-diaminoacridine hydrochloride... 

A good understanding of the properties of water is thus essential as we move to more complicated systems. We have been involving in the study of aqueous solution of many important biological molecules, such as acetylcholine, Gramicidin, deoxydinucleoside phosphate and proflavin, and DNA, etc., first at the Monte Carlo level and slowly moving to the molecular dynamics simulations. We will discuss some of the new results on the hydration structure and the dynamics of B- and Z-DNA in the presence of counterions in the following. 

As described in section 4.1, the DNA double helix must unwind to allow access ofthe polymerase enzymes to produce two new strands ofDNA. This is facilitated by DNA gyrase, the target of the quinolones. Some agents interfere with the unwinding of the chromosome by physical obstruction. These include the acridine dyes, of which the topical antiseptic proflavine is the most familiar, and the antimalarial acridine, mepacrine. They prevent strand separation by insertion (intercalation) between base pairs from each strand, but exhibit very poor selective toxicity. 

The acridine dyes, including proflavine, acriflavine and aminacrine, have also been employed for skin disinfection and treatment of infected wounds or burns. They are slow-acting and mainly bacteriostatic in effect, with no useful fungicidal or sporicidal... 

Acridine dyes used as antiseptics, i.e. proflavine and acriflavine, will react specifically with nucleic acids, by fitting into the double helical structure of this unique molecule. In so doing they interfere with its function and can thereby cause cell death. 

C19H23lN8012P)2(C13H12N3)2(CH40)-15 H20 Proflavine 5-iodocyt-idylyl-(3 — 5 )-guanosine, methanolate, pentadecahydrate (AC-CYGB10)178... 

C2 Z = 4 Dx = 1.41 R = 0.102 for 4,115 intensities. The structure is a 3 2 complex of proflavine and CpG. The asymmetrical unit contains one CpG molecule, 1.5 proflavine molecules, 0.5 sulfate ion, and 11 5 water molecules. Two CpG molecules form an antiparallel, Watson-Crick, miniature duplex, with a proflavine intercalated between the base pairs through the wide groove. The double helix has exact (crystallographic), two-fold symmetry, and the crystallographic, two-fold axis passes through the C-9-N-10 vector of the intercalated proflavine. A second and a third molecule of proflavine are stacked on top of the C - G pairs ... 

C19H24N8OllP)(C13HuN2) 8.5 HaO Proflavine cytidylyl-(3 - 5 )-adenosine-8.5 H20214... 

In addition to the intercalated proflavine, there is a proflavine molecule that is sandwiched by adjacent, CpA dimer duplexes. The intercalated proflavine stacks more extensively with the C-C pair than with the A-A pair. The sandwiched proflavine stacks extensively with both the A - A and C-C pairs. Both proflavine molecules exhibit disorder. In each... 

C10H14N5O13P6)2(C10H8N2)2 Zn2 4 HaO [Adenosine 5 -zinc(II) (2,2 -bipyridyl triphosphate)]2, tetrahydrate (ATPPZN)239 C12H15N505 (5 -Deoxy-5 -adenosine-5 -yl)acetic acid (DOADAC)240 (C19H26N8O11P)(C]l3H11N3)>10 HaO Cytidylyl-(3 — 5 )-adenosine-proflavine, decahydrate (CPAPRF)241... 

C13H12N3+ C19H24N8O12P- 0.5 Proflavine-cytidylyl-(3— 5 )-guanosine, sulfate, hydrate PFCYGU10 43 306... 

CI9HteN8OI1P-C13H11Na-10 h2o CytidylyI-(3 — 5 )-adenosine-proflavine complex, decahy- CPAPRF 43 335... 

C2oH25N10010P -2 C13H12N3+ 04S2- Adenylyl-(3 — 5 )-adenosine phosphate bis(proflavin ADPAPF 43 373... 

Koglin E., Sequaris J.M., Interaction of proflavine with DNA studied by colloid surface enhanced resonance Raman-spectroscopy, J. Molecular Struct. 1986 141 405-409. 

Several complexes that involve intercalation of an acridine in a portion of a nucleic acid have been studied by X-ray crystallographic techniques. These include complexes of dinucleoside phosphates with ethidium bromide, 9-aminoacridine, acridine orange, proflavine and ellipticine (65-69). A representation of the geometry of an intercalated proflavine molecule is illustrated in Figure 6 (b) this is a view of the crystal structure of proflavine intercalated in a dinucleoside phosphate, cytidylyl- -S ) guano-sine (CpG) (70, TV). For comparison an example of the situation before such intercalation is also illustrated in Figure 6 (a) by three adjacent base pairs found in the crystal structure of a polynucleotide (72, 73). In this latter structure the vertical distance (parallel to the helix axis) between the bases is approximately... 

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