Wavelength nm

Figure 3 Absorption spectrum of chloramphenicol in ethanol.

Absorbance Fluorescence

300 400 500

Wavelength (nm)

Figure 4 Absorption spectrum of chlorpromazine in ethanol.

In laser flash photolysis experiments (Table 1) direct excitation of CLP produced a Ti state with high efficiency (Or = 0.52) and a triplet-triplet absorption maximum at 460 nm. The lifetime of the transient was 10 (is. No detectable transient was generated from the other compounds under the same conditions. On the other hand, all compounds were able to quench efficiently the lowest triplet state of phenanthrene in ethanol (triplet energy of 62 kcal mol"1) and xanthone in ch3cn (triplet energy of 74 kcal mol"1). This evidence strongly supports the hypothesis that the triplet state properties of the other molecules (quantum yield and/or lifetime) generated by direct irradiation are below the detection limit of our instrument. In sensitised conditions (i.e. in presence of phenanthrene or xantone) 13-cis-retinoic acid showed a detectable triplet-triplet absorption at 420 nm (t = 40 p.s). Such a sensitised triplet formation was not observed for nifedipine and chloramphenicol.

A parallel trend was observed between the triplet and the singlet oxygen formation quantum yields. A well-detectable singlet oxygen formation was observed for chlorpromazine (Oa = 0.48) and no signal was generated from the other compounds (Table 1).

As regards photostability 13-ci'j-retinoic acid (Fig. 5) shows a disappearance in its 344 nm peak and a new peak appeared at 261 nm. No isosbestic point was detected, indicating that more than one intermediate was involved in the reaction. No significant difference was observed between air-saturated and nitrogen-flushed solutions during irradiation.

Nifedipine, on the other hand, exhibited three isosbestic points (Fig. 6) indicating the presence of a single intermediate in the decay process. The 357 nm broad peak decreased during irradiation while a new peak developed at 282 nm. Again the presence of oxygen did not modify the degradation spectra and the decay kinetics (Fig. 7).

On the contrary, chlorpromazine, showed a strong influence of oxygen upon its decay mechanism: oxygen strongly reduced the degradation rate (Fig. 8) converting the reaction from an apparent first-order to an apparent zero-order (no concentration dependence was studied to date in order to test this hypothesis). Since the first triplet state of this molecule is strongly efficient (Table 1) in producing singlet oxygen (92% of triplets generated singlet oxygen under our conditions), an alternative decay pathway of this excited state could be the limiting step in the degradation pathway.

As regards the photosensitising properties (Table 2), 13-cis-retinoic acid appeared to be quite inefficient toward all the substrates studied by us.

Nifedipine, on the other hand, was a fairly efficient photosensitiser toward TrpEE. The sensitisation process competed with the photodegradation but also more efficient (Kv(Sens) = 4 x 10"8 M s"1 and t(trpee) = 108 s, while Kv(degr) = 1 x 10"6 M s"1 and t(nif) = 52 s), although large excess of nifedipine was needed in order to achieve the complete modification of TrpEE (K.v(sens) = 4 x 10"8 M s"1 and t(tipee) = 108 s, while Kv(degr) = 1 x 10"6 M s"1 and t(nif) = 52 s). No degradation of histidine, albumin or cholesterol was observed with nifedipine, probably because the rate of photosensitised modification of these targets was substantially lower than that typical of nifedipine photodegradation. Moreover, differential spectra and preliminary analysis with elution chromatography, showed no dark interaction between nifedipine and albumin. Analogously, lysozyme activity was not modified after irradiation in the presence of nifedipine.

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