The data indicate that the device successfully reduced the number of selected pathogens in PCs. Despite the fact that significant differences exist between treated and control in-vitro variables, it is speculated that the clinical effectiveness of both products will not be significantly different, based on comparison to historical data for products in routine clinical use today.
A series of para-substituted N-methyl-N-phenylnitrenium ions (N-(4-biphenylyl)-N-methylnitrenium
ion, N-(4-chlorophenyl)-N-methylnitrenium ion, N-(4-methoxyphenyl)-N-methylnitrenium ion, and N-(4-methylphenyl)-N-methylnitrenium ion) were generated through photolysis of the appropriately substituted
1-aminopyridinium salt. Laser flash photolysis using UV−vis detection as well as photoproduct analysis verified
that the expected nitrenium ions were formed cleanly and rapidly following photolysis. Laser flash photolysis
with time-resolved infrared detection allowed for structural characterization of the nitrenium ions through
observation of a symmetrical aromatic CC stretch in the region 1580−1628 cm-1. The specific frequencies
reflect the degree of quinoidal character present in each phenylnitrenium ion (i.e., the degree to which the
nitrenium ion resembles a 4-iminocyclohexa-2,5-dienyl cation). The 4-methoxy derivative shows the highest
frequency CC stretch, indicating that this strongly π-electron-donating substituent imparts more quinoidal
character, and the 4-chloro derivative shows the lowest frequency CC stretch, suggesting that it possesses
the least quinoidal character. Quantum calculations using density functional theory (BPW91/cc-pVDZ) were
carried out on the same nitrenium ions. The theoretically derived IR frequencies showed excellent quantitative
agreement with the experiment. The computed structures show significant bond length alternation in the phenyl
rings, shortened C−N bond lengths, and substantial positive charge delocalization into the phenyl rings. All
of these effects are more pronounced with increasing π-donating character of the ring substituent. Arylnitrenium
ions are well described as 4-iminocyclohexa-2,5-dienyl cations.
We are developing a technology based on the combined application of riboflavin (RB) and light for inactivating pathogens in blood products while retaining the biological functions of the treated cells and proteins. Virus and bacteria reduction measured by tissue culture infectivity or colony formation with UV light alone and in combination with RB yield equivalent results. The effects of RB as a sensitizing agent on DNA in white cells, bacteria and viruses in combination with UV light exposure have been evaluated. UV-mediated DNA degradation in Jurkat T cells and leukocytes in plasma as measured by the FlowTACS assay was significantly increased in the presence of RB. Agarose gel electrophoretic analysis of DNA in Escherichia coli and leukocytes in plasma demonstrated enhanced DNA degradation in the presence of RB. UV light in combination with RB prevented the reactivation of lambda phage compared with samples irradiated in the absence of RB. UV-mediated oxidative damage in calf thymus DNA was also enhanced in the presence of RB. These observations clearly demonstrate that the presence of RB and UV light selectively enhances damage to the guanine bases in DNA. These data also suggest that the type and extent of damage to DNA for virus in the presence of RB and light make it less likely to be repaired by normal repair pathways available in host cells.
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