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Vol. 3 INTERNATIONAL JOURNAL OF PHOTOENERGY 2001

Photochemical reactions of metal nitrosyl complexes.Mechanisms of NO reactions with biologically

relevant metal centers

Peter C. Ford

Department of Chemistry, University of California, Santa Barbara, CA 93106, USA

Abstract. The discoveries that nitric oxide (a.k.a. nitrogenmonoxide) serves important roles in mammalianbioregulation and immunology have stimulated intense interest in the chemistry and biochemistry of NOand derivatives such as metal nitrosyl complexes. Also of interest are strategies to deliver NO to biologicaltargets on demand. One such strategy would be to employ a precursor which displays relatively low thermalreactivity but is photochemically active to release NO. This proposition led us to investigate laser flashand continuous photolysis kinetics of nitrosyl complexes such as the Roussin’s iron-sulfur-nitrosyl clusteranions Fe2S2(NO)42− and Fe4S3(NO)7− and several ruthenium salen and porphyrin nitrosyls. These includestudies using metal-nitrosyl photochemistry as a vehicle for delivering NO to hypoxic cell cultures in order tosensitize γ-radiation damage. Also studied were the rates and mechanisms of NO “on” reactions with modelwater soluble heme compounds, the ferriheme protein met-myoglobin and various ruthenium complexesusing ns laser flash photolysis techniques. An overview of these studies is presented.

1. INTRODUCTION

In the early 1990’s, we initiated studies in this labora-tory and collaboratively with the RIKEN (Japan) groupof Mikio Hoshino into the photochemical reactions ofmetal nitrosyl complexes. This interest was stimulatedby Larry Keefer and David Wink at the National CancerInstitute, who drew our attention to (then) recently dis-covered roles of nitric oxide as an intercellular bioregu-latory agent in mammals and as a toxic species formedin immune response. Our involvement has grown into amajor effort concerned with the photochemistry of ni-trosyl complexes and with mechanistic investigationsof related thermal reactions. Described here are severalrelated projects concerned with the quantitative pho-tochemistry of metal complexes, aspects of which arealso concerned with fundamental chemical propertiesof NO or other reactive nitrogen oxide species havingpotential biological relevance.

The chemistry of nitric oxide was once largely theprovince of atmospheric science, although the interac-tion of NO and transition metals provided interestingtextbook examples of coordination modes dependentupon electronic properties. However, the discoveries inthe late 80’s that NO has key roles as a bioregulatorin the cardiovascular system and in neurobiology andis formed in toxic concentrations during immune re-sponse to pathogens has induced considerable interest[1–3]. These roles and the apparent relationship of over-or under-production of NO to various disease stateshas led to a remarkable outpouring of contributions tothe chemical, biological and biomedical literature [4, 5].Nonetheless, despite this activity, fundamental issuesregarding the condensed phase chemistries of NO and

related species such as nitrogen dioxide (NO2), perox-ynitrite (OONO−) and hydrogen nitrosyl (HNO) need fur-ther analysis. For example, althoughmetals are primarytargets in the biological chemistry of NO, until recentlylittle attention had been given to the mechanisms forthe formation of metal-NO bonds.

Metal nitrosyls can also be seen as useful deliveryagents of nitric oxide and, in particular, hold promisefor the photochemical delivery of NO to biologicaltargets. Photochemical delivery from thermally stablecompounds would allow for specific targeting throughcontrol of irradiation areas and intensities. Since lighttransmission of mammalian tissues is more effectiveat longer wavelengths, complexes photosensitive to redlight are of special interest.

Scheme 1 is a cartoon illustrating different strategiesfor NO photoproduction currently under study in thislaboratory. The first two involve metal nitrosyl com-plexes, and there is a rich history of nitrosyl complexphotochemistry, especially that involving metallopor-phyrins [3]. The third (the “indirect method”) generatesNO not by labilization of an M−NO bond but from thelabilization of an O−N bond of coordinated nitrite. Re-viewed in the sections below are examples from each ofthese approaches.

2. IRON SULFUR NITROSYL CLUSTERS(ROUSSIN’S ANIONS)

Although the anions of Roussin’s black salt,Fe4S3(NO)7− (RBS) and of Roussin’s red salt,Fe2S2(NO)42− (RRS), were first described in themid-19th century [7], their photochemistry has onlyrecently drawn attention. The water soluble Roussin’s

162 Peter. C. Ford Vol. 3

INDIRECT RELEASE

SENSITIZED RELEASE

Other metal nitrosyls

Metalloporphyrins

DIRECT RELEASE

LnM O N

O

hνLnM O + NO

LnM NO+

LnM(NO)*hν

LnM(NO)

Fe2S2(NO)42−hν Fe4S3(NO)7− + NO + ?

NO+

L

M

?

hν

L

M

NO

Scheme 1. Photochemical strategies for NO delivery.

ON

Fe

S

SS

Fe(NO)2

Fe(NO)2Fe(NO)2

1−

RBS

NO

NO

S

S

FeFeON

ON

2−

RRS

salts were chosen to study in part because their opticalspectra have absorptivities into the red, a featureattractive for possible use in tissues. The RBS anionhas been the subject of several studies with vascularand brain tissues as a drug for the thermochemicalor photochemical delivery of NO [8, 9]; indeed, abiological assay (rat tail artery relaxation) was used todemonstrate the NO release from RBS upon photolysisin buffer solutions [8]. The red salt anion RRS hasprimarily been studied as a synthetic precursor; for ex-ample, it reacts with haloalkanes to form red “esters”,Fe2(SR)2(NO)4 [10]. The quantitative photochemistryof neither the anions nor the esters had receivedattention until our recent studies [11–14].

As their names imply, the Roussin’s red and blacksalts are highly colored compounds with strong broadabsorptions with moderately high extinction coeffi-

cients (1–3×103 M−1cm−1) that suggest charge transfercharacter. There is clearly a need for a better under-standing of the spectroscopy and photoactive excitedstates of these iron sulfur nitrosyl clusters, especiallythe lowest energy excited states (LEES), since the inde-pendence of quantum yields to the irradiation wave-length (λirr) would be consistent with the cascade frominitially formed states to a common LEES (see below).Extended Hückel molecular orbital calculations suggestthat the LUMO has some Fe− Fe and Fe− S and Fe−NOantibonding character [15, 16]; hence excitation mightbe expected to lead to cluster fragmentation. However,in analogy to other iron sulfur clusters [17], the metalcenters are likely to be antiferromagnetic coupled Fe3+

and/or Fe2+ with negatively charged nitrosyls. In such acase the LEES may be NO-to-iron charge transfer stateswith enhanced lability of the Fe−NO bonds.

Vol. 3 Photochemical reactions of metal nitrosyl complexes. Mechanisms of NO reactions … 163

2.1. Photoreactions of RBS. Roussin’s black salt isthermally stable in aerated aqueous solutions. Photoly-sis leads to optical density decreases broadly across thevisible spectrum (Figure 1). The quantum yields for RBSdisappearance (Φd) for a variety of irradiation wave-lengths (λirr). These showed little dependence on λirr,giving an average Φd value of ∼ 10−3 from λirr 313to 546nm in aerated aqueous solutions [12]. However,in deoxygenated solutions, RBS showed no net photo-chemistry when irradiated continuously, or upon re-peated laser excitation. The importance of an oxidantto the net photochemistry is illustrated by the obser-vation that solutions equilibrated with 1atm PO2 gavequantum yields ∼ 5× that of air equilibrated solutions,in keeping with the higher [O2].

300 400 500 600 700

Wavelength (nm)

0

0.1

0.2

0.3

0.4

Abso

rban

ce

10

8

6

4

2

Curren

t(nA)

0 80 160 240 320 400Time (s)

hν on

hν off

Figure 1. Spectral changes upon light photolysis of an aer-

ated pH 7.0 solution of Roussian’s black salt. Inset: detec-

tion of NO released using a WPI NO sensor with calibrated

sensitivity 0.66nA/µM. Initial [RBS] = 15µM; ∆[RBS] =−1.51µM. ∆[NO] determined electrochemically = 9.1µM.

Electrospray mass spectroscopy (ESMS) was used toidentify products of the black salt photolysis in aer-ated aqueous solution [12]. The RBS anion itself waswell represented in the ESMS, showing both the parentat 530m/z, as well as a series of three peaks showinglosses of NO at successive −30m/z intervals. Nitrite at47m/z was also a primary product, accompanied by aweak nitrate peak at 63m/z. Analysis for ferrous ionsby 1, 10 phenanthroline addition indicated nearly quan-titative formation of ferrous ion and electrochemicalexperiments demonstrated that ∼ 6 NO were releasedfrom each cluster, i.e., equation (1), (the unaccountedelectron “[e−]” is presumably consumed by O2 in theseaerated media).

Fe4S3(NO)7−hν=⇒O2

3.9Fe2+ + 5.9NO+ 3S2−+?. (1)

Flash photolysis studies of the RBS system havebeen carried out using time resolved optical (TRO) and

time resolved infrared (TRIR) [18] spectroscopic tech-niques to probe the spectra and dynamics of possi-ble reactive intermediates. Two transient species wereformed in roughly equal concentrations, both of whichare trapped by NO to reform RBS. In this context re-action sequence described in Scheme 2 was proposedwhere X and Y are considered to be isomers of the “un-saturated cluster” Fe4S3(NO)6−. The combined quan-tum yields (ΦX + ΦY) for formation of X and Y has alower limit of 0.062 which can be compared to valuesof < 10−6, 0.0011 and 0.0042 determined in deaer-ated, aerated and oxygenated solutions, respectively,for the quantum yields (ΦRBS) for RBS decompositionaccording to equation (1) under continuous photolysisconditions. The back reactions with NO have the sec-ond order rate constants kNOX = 1.3× 107 M−1s−1 andkNOY = 7× 105 M−1s−1, and it is these rapid back reac-tions in competition with trapping by oxygen that de-termines the quantum yields for photodecomposition.

Products

ProductskY[O2]

kX[O2]

Y

X

kNOY[NO]

kNOX[NO]

(−NO)φYIa

(−NO)φXIa

Fe4S3(NO)7−

Scheme 2.

2.2. Photoreactions of RRS. Roussin’s red salt an-ion is only moderately stable in aerated aqueous so-lutions at neutral pH, and reacts to give RBS over thecourse of a few hours in the dark. When irradiated withnear UV or visible light, this process was markedly ac-celerated and gives a λirr independent quantum yieldof ∼ 0.14 for conversion of RRS [12]. The RBS productwas identified from optical, FTIR and ESMS spectra: thelatter also showed the formation of nitrite and sulfide.Electrochemical NO analysis indicated that 0.5 moles ofNO are released for each mole of RRS converted to RBS.

Flash photolysis studies of Roussin’s red salt di-anion, Fe2S2(NO)42− (RRS) demonstrated high quan-tum yield formation of an intermediate believed to beFe2S2(NO)32− formed by photodissociation of NO. Thisspecies reacts competitively with nitric oxide via sec-ond order kinetics (kNO = 9.1 × 108 M−1s−1) to reformRRS and with dioxygen (kOx = 5.6 × 107 M−1s−1 ) togive a secondary intermediate [14]. The latter speciesis the likely precursor of the eventual photoproduct,Fe4S3(NO)7− (RBS). Scheme 3 illustrates the proposedscheme leading to these products.


RBS + S2−+ Fe2S2(NO)4−2

Fe2S2(NO)3− (Iii )

kOX = 5.7× 107 M−1s−1

O2

Fe2S2(NO)32−(Ii)+NOφ1Ia

kNO = 9.1× 108 M−1s−1Fe2S2(NO)4−2

Scheme 3.

The Fe2S2(NO)42− anion is also photoreactive indeaerated solutions, but with a much reduced Φd. Indeaerated acetonitrile the Roussin’s black salt dianion,Fe4S3(NO)72− (BSD) is the iron containing product ascharacterized by FTIR and UV-vis. However, in deoxy-genated aqueous solutions only the RBS monoanionwas observed, leaving our electron count incomplete.This discrepancy was eliminated by the discovery thatunder these conditions, N2O is also a reaction productwith the ∆N2O/∆RBS ratio of 0.5 ± 0.03. This appar-ently comes from the direct reduction of NO by BSD(∆E = +0.11V) to give the nitroxyl anion, NO−, fol-lowed by formation of nitrous oxide in protic solvents(2NO− + 2H+ → H2O+N2O). The following stoichiome-try in deaerated protic solvents results.

2H+ + 4Fe2S2(NO)42−

hν−−→ 2Fe4S3(NO)7− + 2S2− +N2O+H2O. (2)

2.3. Radiation sensitization using RRS. The useof these complexes to deliver NO to biological targetswas the subject of collaborative studies at the Radia-tion Biology Branch at the National Cancer Institute inBethesda, MD [12]. Nitric oxide has long been knownto sensitize hypoxic (oxygen deficient) cell cultures togamma radiation damage [19]. The Roussin’s salts weretherefore used to deliver NO photochemically to hy-poxic cultures of Chinese hamster V79 cells in order toprobe possible effects upon the γ-radiation sensitivityof these cells.

Figure 2 shows the logarithmic survival rate of thecell cultures when subjected to varied irradiation doses.As can be clearly observed, treatment of the cells withRRS had little effect on the survival, but simultane-ous white light irradiation greatly decreased the sur-vival fractions of the cell cultures when exposed to γ-radiation. Visible light irradiation of the RRS incubatedcell cultures without γ-radiation, had little effect onsurvival fractions. Sensitization up to 100 fold of radia-tion induced cell death was observed for this and otherred salt concentrations. These results clearly provide aproof-of-concept example for delivery of NO to biolog-ical targets by photochemical means.

2.4. Roussin’s Red “Esters”. We have extendedthese investigations to various sulfur functionalized

0 5 10 15 20 25

Dose (Gy)

10−2

10−1

100

SurvivingFrac

tion

+RS/WL

+RS/No WL

Control

Figure 2. Survival of V79 cells exposed to γ radiation un-

der hypoxic conditions in the absence (open circles) or pres-

ence of 500µM RRS with (closed circles) or without (open

squares) light exposure. The dashed line on the plot indi-

cates the responce of cells exposed to γ radiation under

fully aerobic conditions.

derivatives Fe2(SR)2(NO)4, the Roussin’s red estersRSE[20], which aremore air stable thanRRS yet remain pho-toactive toward NO dissociation. These can be preparedfrom the reaction of RRSwith the precursor R-X. Of par-ticular interest is the possibility of varying the group Rto manipulate the properties such as reactivity, solubil-ity, optical spectral profile or biological specificity of aunit containing the iron sulfur clusters.

For example, the sulfonated derivative, Na2[Fe2(SCH2CH2SO3)2(NO)4] shows both good thermal sta-bility and high water solubility. The photolysis of thiscomplex in aerated solutions results in the formation of3.8 moles of NO per mole of complex photoconverted.The other products included Fe2+ ions and the free thiolligands, observed by ESMS. The quantum yield for NOformation ΦNO in aerated aqueous solution is ∼ 0.2, thehighest value for a Fe− S−NO complex yet observed.However, these RRS esters have electronic spectra sim-ilar to that of RRS itself and do not adsorb sufficientlyat longer wavelengths for in vivo studies.

To address this issue we are preparing other RREcompounds where the R-groups have a chromophore

RSE

R

S

S

R

FeFeNO

NO

ON

ON


such as a dye molecule which might act as an in-tramolecular photosensitizer of the Fe2S2(NO)4 moi-ety. For example, we have now prepared [20] the RRSester with R2 = a derivative of protoporphyrin IX (PPIX-RSE) and have characterized it by a number of physi-cal methods including high resolution mass spectrom-etry. Although the absorption spectra is almost entirelydominated by the porphyrin chromophore, the photo-physics and photochemistry of this species are stronglyinfluenced by the presence of the Roussin’s cluster. Theintensity of emission from the free base porphyrin is∼ 90% quenched and the lifetime is correspondinglyshorter. Furthermore, direct excitation of the porphyrinQ-band absorptions with 546nm light leads to NO re-lease from the cluster with a quantum yield clearly con-sistent with intramolecular photosensitization of reac-tions at the RRS cluster center.

RSE-PPIX

(NO)2Fe(NO)2

Fe

SS

O C OO

CO

NH N

N HN

3. PHOTOREACTIONS OF RUTHENIUMNITROSYL PORPHYRINS

Thermal stability is a necessary characteristic for aphotoactive NO carrier. It was this feature that turnedour attention to the ruthenium porphyrin complexesRu(P)(X)(NO) (e.g., P = TPP (tetraphenylporphyrin) orOEP (octaethylporphyrin)) since ruthenium nitrosylsare generally robust. Porphyrins have strong absorp-tions in the red, thus M(P)NO species may have attrac-tive properties in this regard. These were first preparedby the reaction shown in equation (3) [21, 22], and quan-titative kinetics studies of this transformation provideda valuable platform for characterizing one mechanismfor metal promoted NO disproportionation [23].

Ru(P)(CO)+4NO −→ Ru(P)(NO)(ONO)+CO+N2O. (3)

The photochemistry of various Ru(P)(NO)(X) isquite rich owing to competitive excited state re-actions [24]. For example, flash photolysis studiesof Ru(TPP)(NO)(ONO) (A) in hydrocarbon solventsdemonstrated that two short-lived intermediates are

formed. The decay kinetics clearly demonstrated thatthe temporal absorbance could be best fit to two ex-ponentials. both of which are [NO] dependent (Fig-ure 3). We have shown that one photoreaction is NOlabilization to give (formally) a Ru(III) intermediateRu(P)(ONO). This is reversible and displays a back re-action with NO with a second order rate constant of2.8 × 108 M−1s−1. The other involves NO2 dissociationto give the transient paramagnetic species Ru(P)(NO)having analogy in stable complexes formed from sim-ple NO addition to FeII(P). Dissociation of NO2 isalso a photoreaction of the manganese nitrito com-plex Mn(TPP)(ONO) (see below) [25]. That NO2 disso-ciation is seen indicates the electronic flexibility of theRu(P)(NO) chromophore, since this (formally) involvesreduction of a {MNO}6 to a {MNO}7 system [26]. Thereturn of this intermediate to the starting nitrosyl ni-trito species is a complicated transformation, involv-ing formation of the dinitrosyl complex Ru(P)(NO)2

0 1×10−5 2×10−5 3×10−5 4×10−5 5×10−5Time (s)

−0.5

−0.4

−0.3

−0.2

−0.1

0

∆Abs(572nm)

Decay of transients formed by 355nm flash photolysisof “Ru(TPP)(NO)(ONO)”

k1obs = 3.7× 105 s−1

k2obs = 6.8× 104 s−1

(in benzene, [NO] = 2.7× 10−3 M)analyzed according to two competitive reactions

Figure 3. Decay of transients formed by laser flash photoly-

sis of Ru(TPP)(NO)(ONO) in benzene solution asmonitored

in the Q-band region.

ON

O

Ru + NO

NO2Ru

NO

+

+ NO

IO

N

Ru

ON

O

hν

Scheme 4.

(I) via a second order reaction of Ru(P)NO with NO(2×107 M−1s−1) followed by further reaction with NO togive Ru(P)(NO)(ONO) plus N2O in analogy to the ther-mal reaction of Ru(P)(CO) with NO to give A, CO andN2O [23] (Scheme 4).

4. RUTHENIUM SALEN NITROSYL COMPLEXES

We have begun to explore another synthetic platform


O

C N

Cl

Ru

N

O

O

N C

B

hν OC N

Ru

Cl

SolO

N C+ NO

Sol = solvent(4)

for ruthenium based NO carriers, namely, the salen-type complexes Ru(R− salen)(X)(NO), (salen = N, N′-bis(salicylidene)-ethylenediaminato dianion). Additio-nal interest in these derives from recent demonstra-tions that Ru(R− salen)(X)(NO) compounds are pre-cursors of oxene and carbene transfer catalysts foralkene asymmetric epoxidations and cyclopropana-tions as well as of Lewis acid catalysts for asymmet-ric hetero Diels-Alder reactions [27]. Since these cata-lysts are activated by light, quantitative evaluation oftheir photochemical properties has multi-dimensionalinterest.

We have carried out preliminary photoreactivity in-vestigations on a representative member of this fam-ily, Ru(salen)(Cl)(NO) (B) in various media [28]. Thesedemonstrate that NO is labilized at 436nm) to give sol-vento Ru(III) analogs (equation (4)) and provide a log-ical model for the photoactivation and solvent depen-dent reactivities of the catalysts noted above.

The thermal reverse reaction to regenerate B (equa-tion (5)) is strongly dependent on the nature of thesolvent, with second order rate constants kNO (298K)ranging ∼ 11 orders of magnitude from 4×107 M−1s−1

in toluene to ∼ 5 × 10−4 M−1s−1 in acetonitrile [28].Superficially, this observation suggests a mechanismwhere Sol dissociation from the Ru(III) center is occur-ring or has occurred at the rate limiting transition statefor Ru−NO bond formation. Such a pathway is consis-tent with the mechanism we proposed for the NO reac-tions with ferri-heme models and metmyoglobin basedon activation parameters measurements [31–33]. How-ever, this mechanism is inconsistent with studies car-ried out on NO substitution for NH3 on the Ru(III) com-plex Ru(NH3)63+ in aqueous solution. In that case, thesecond order reaction of NO is too fast to be attributedto NH3 dissociation and activation parameters are con-sistent with associative attack of the NO radical on thed5 metal center [34].

Ru(salen)(Cl)(Sol)+NOkNO−→ Ru(salen)(Cl)(NO)+ Sol. (5)

Another example of this family is Ru(salen)(NO)(ONO) described by Wilkinson et al. [29]. In contrastto the porphyrin analog A, photochemical studies ofthis indicate the formation of a single intermediate,Ru(salen)(ONO)(Sol) (Sol = solvent) generated by NOloss [30]. In preliminary studies, we have also developed

procedures for the synthesis of the ionic compounds[Ru(salen)(H2O)(NO)]X and have demonstrated thattheir photochemistry in aqueous solution is analogousto that of B [30].

The salen type ligands are easily modified to changethe electronic and steric characteristics of the ligands.In this context, we are beginning an exploratory ef-fort to engineer new molecular species of the typeRu(L)(X)(NO) (L = various salen-type ligands) with ini-tial goals of tuning the spectroscopic properties. Forexample, standard salen complexes have relatively lowabsorptivities in the visible region (Figure 4, dashedline); while those of the more conjugated salophen lig-ands (see drawing) show much stronger bands in thered (Figure 4 solid line), yet qualitatively have photore-activity properties similar to those of B [27]. The goal isto prepare and characterize a related series of new com-pounds where systematic variations lead to predictabledifferences in the absorption spectra, solubilities andphotochemical reactivities.

4.1. Photochemistry of Mn(III) and Cr(III) nitritocomplexes. This project is an example of serendip-ity. We were interested in demonstrating NO formationfrom the photochemical cleavage of an O−N bond ofcoordinated nitrite (M−O−NO → M = O + NO). Thiswas an early suggestion for one of the photoreactionpathways of Ru(P)(NO)(ONO) and had been described

6005004003000

10

20

30

40×103

εin

l/(m

ol*cm

)

λ in nm

Figure 4. Optical Spectra of t-Bu derivatives of B (dashed

line) and its salophen analog (solid line) in acetonitrile so-

lution.


= TPP

+ N2O3

MnIII

ON

O

kis om

MnIII

ON

O

+ NO2

+ NO2

MnIITPP(NO)

+ NO

+ O2

MnII

MnIITPP(O2)

hν,−NO2

Φ = 0.045MnII(TPP)(ONO)

hν Φ ∼ 10−4

O

MnIV

+ NO

Scheme 5.

Ru((tBu)4salophen)(Cl)(NO)

Cl

Ru

NO

NN

OO

tButBu

tBu tBu

as a pathway for the photolysis of Mn(TPP)(ONO) (C)[34]. However, when we (with Hoshino) examined theflash photolysis kinetics of C [25], the dominant pho-toreaction was homolytic cleavage of the M−O bond togive NO2 (Φ = 0.045) accompanied by formation of theMn(II) intermediate Mn(TPP). While this provided theopportunity to examine the quantitative reactivities ofMn(TPP)with NO, O2 andNO2 (Scheme 5), it also piquedour interest in exploring what parameters would lead tothe photolytic generation of NO from O-coordinated ni-trite. It had been previously shown that the porphyrincomplexes Mo(TPP)(O)(ONO) and Cr(TPP)(ONO) un-dergo irreversible β-cleavage to give Mo(TPP)(O)2 andCr(TPP)(O) in benzene [35].

Hoshino’s results with Cr(TPPP)(ONO) [35] clearlysuggested that with a sufficiently oxophilic metal, co-ordinated nitrite can serve as a photochemical NO pre-cursor. In this context, we turned to the amine com-plexes of Cr(III) to see if this behavior had general-ity beyond the metalloporphyrins. Another attractiveproperty of these is the solubility in water, a featurelikely to be desirable in biomedical applications. Thefirst of such species examined was Cr(NH3)5(ONO)2+.The optical absorption spectrum of this is defined by

the Laporte forbidden ligand field (d-d) transitions at482nm (ε = 43M−1cm−1) and 356nm with an intensity(37M−1cm−1) consistent with the next higher energyquartet band but in the region where the internal lig-and n-π∗ band of the nitrito functionality is expected.When freshly prepared aqueous solutions (1mM, pH 7)were irradiated with the white light from a 75W highpressure xenon arc lamp, NO formation was monitoredelectrochemically. Quantum yields were not evaluatedowing to the instability of this species to thermal reac-tions under photolysis conditions. Furthermore, it wasapparent that the Cr(NH3)5(ONO)2+ ion was undergo-ing other photochemistry, namely labilization the am-mine trans to the nitrito ligand [36].

Our attention then turned to the Cr(III) com-plex trans-Cr(cyclam)(ONO)2+ (D, cyclam = 1,4,8,11tetraazacyclotetradecane) (Figure 5). When D was sub-jected to continuous photolysis (λirr = 436nm) indeaerated pH 7 aqueous solution (or under an Ar orNO atmosphere), a gradual shift of the absorption spec-trum to that of the trans-CrIII(cyclam)(H2O)(ONO)+

cation was observed. The spectral changes closelymatch those seen in the acid hydrolysis of D at pH 2,and are analogous to those reported for the acid hy-drolysis of trans-[Cr(en)2(ONO)2]+. Thus, we concludethat the net photoreaction under these conditionsis simple photoaquation with a small quantum yield(Φaq = 0.0092±0.0008). This is consistent with the verylow photoreactivity that has been noted for other trans-Cr(cyclam)X2

+ cations (e.g., X = Cl) when subjected toligand field excitation.

The spectral changes were entirely differentwhen D was photolyzed in aerated aqueous so-lutions at different λirr ranging from 365nm to546nm. A new species ws identified provisionally as


t-CrV(cyclam)(O)(ONO)2+

E

Ox

t-CrIV(cyclam)(O)(ONO)+ + NOhν(Φ = 0.27)

kNO

t-CrIII(cyclam)(O)(ONO)2+

D

hν(Φ = 0.009)

t-CrIII(cyclam)(H2O)(ONO)2+ + NO2−

Scheme 6.

+ONO−

NN

Cr(III)N

N

ONO−

0

0.05

0.10

0.15

0.20

0.25

0.30

0.35

300 350 400 450 500 550

Figure 5. Spectrum of trans-Cr(cyclam)(ONO)2+ in aque-

ous solution.

trans-CrIV(cyclam)(O)(ONO)+, which was trappedby oxygen to give the CrV complex E with an overallquantum yield of 0.27 at 436nm. NO formation wasconfirmed electrochemically, and flash photolysisindicated that the primary photoproduct reacts readilywith NO (kNO = 3.1× 106 M−1s−1) to reform D in com-petition with O2 trapping to give E. (Scheme 6) [36].

5. SUMMARY

This article has summarized recent studies in this lab-oratory which have been concerned with the photo-chemistry of metal nitrosyls. Work on the Roussin’ssalts has demonstrated the concept of coordinationcomplexes as photochemical NO delivery agents to bi-ological targets, leading to sensitization of cell to γ-radiation damage. Ongoing flash photolysis studies toelucidate mechanisms for the photochemical reactionsof the black and red salts have been summarized.The ester complexes such as, Fe2(SR)2(NO)4, especiallythose with red sensitive chromophores hold consid-erable promise as more effective delivery agents. Theruthenium nitrosyl complexes such as the porphyrinsare very stable and release NO upon photolysis How-ever the salen type complexes are potentially moreattractive owing to the ability to easily tune the spec-troscopic and reactivity properties by modifying the

ligands. Lastly were described several complexes of ox-ophilic metals that activate the nitrite ion toward pho-todecomposition.

ACKNOWLEDGMENTS

This work was supported by the National Science Foun-dation (CHE 9400919 and CHE 9726889) and by a Col-laborative UC/Los Alamos Research (CULAR) Initiativegrant from Los Alamos National Laboratory. TRO ex-periments were carried out on systems constructedwith instrumentation grants from the U.S. Departmentof Energy University Research Instrumentation GrantProgram (No. DE-FG-05-91ER79039) and from the Na-tional Science Foundation. The following students andpostdoctoral fellows in my laboratory have contributedto the studies described in this review: Katrina M. Mi-randa, Brian Lee, James L. Bourassa, Malcolm DeLeo,CarmenWorks, Christa Conrado, Dr. Setsuko Kudo, andDr. Ivan Lorkovic. I also thank Dr. David Wink of theNational Cancer Institute (Bethesda MD, USA) and Dr.Mikio Hoshino (RIKEN, Japan) with whom we have col-laborated.

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