Efficient Direct Nitrosylation of α-Diimine Rhenium Tricarbonyl Complexes to Structurally Nearly Identical Higher Charge Congeners Activable towards Photo-CO Release

The reaction of rhenium α-diimine (N-N) tricarbonyl complexes with nitrosonium tetrafluoroborate yields the corresponding dicarbonyl-nitrosyl [Re(CO)2(NO)(N-N)X]+ species (where X = halide). The complexes, accessible in a single step in good yield, are structurally nearly identical higher charge congeners of the tricarbonyl molecules. Substitution chemistry aimed at the realization of equivalent dicationic species (intended for applications as potential antimicrobial agents), revealed that the reactivity of metal ion in [Re(CO)2(NO)(N-N)X]+ is that of a hard Re acid, probably due to the stronger π-acceptor properties of NO+ as compared to those of CO. The metal ion thus shows great affinity for π-basic ligands, which are consequently difficult to replace by, e.g., σ-donor or weak π-acids like pyridine. Attempts of direct nitrosylation of α-diimine fac-[Re(CO)3]+ complexes bearing π-basic OR-type ligands gave the [Re(CO)2(NO)(N-N)(BF4)][BF4] salt as the only product in good yield, featuring a stable Re-FBF3 bond. The solid state crystal structure of nearly all molecules presented could be elucidated. A fundamental consequence of the chemistry of [Re(CO)2(NO)(N-N)X]+ complexes, it that the same can be photo-activated towards CO release and represent an entirely new class of photoCORMs.


Introduction
The growing trend of antimicrobial resistance (AMR) poses a serious threat to the public's health, making it more and more difficult to prevent and treat related diseases. Thousands of deaths have been attributed to AMR infections according to WHO findings published in 2018 [1], with an estimated death toll of millions of cases per year by 2050 if the appropriate measures are not taken [2]. With the increasing difficulty of major pharmaceutical companies to meet the demand of new antibiotics discovery and production, universities are contributing to the finding of new classes of active compounds. Pathogens, however, are likely to adapt rapidly and become resistant to new drugs if conventional medicinal chemistry approaches remain based exclusively on organic molecules, also in light of the fact that the majority of drugs in clinical development are modified versions of already-approved antibiotics [3].
There is an increasing awareness in academia of the potential of metal complexes to act as the new class of molecules for the purpose. Indeed, the unique chemistry and larger variety of 3D geometries of metal compounds can address targets and modes of action unavailable to organic molecules. In the last decade, complexes of virtually all transition

Synthesis of fac-[Re(CO)2(NO)(N-N)X] + Species
The chemistry of the fac-[Re(CO)2(NO)] 2+ core is essentially dominated by cyclopentadienyl (Cp) species of general formula [CpRe(CO)2(NO)] + . These compounds are most often prepared by reaction of the corresponding [CpRe(CO)3] with either NO2PF6 [29], NOHSO4 [30], or NOBF4 [31,32]. The last two reagents were successfully used in the preparation of fac-[Re I (CO)2(NO)X3] − [24,27], and of the two, the latter appeared to us the most convenient as the procedure involves simple addition of the nitrosonium tetrafluoroborate salt in a CH2Cl2 (DCM) solution of the rhenium tricarbonyl complex [32]. The reaction has also the advantage of producing an ion pair from the initially introduced components with, theoretically, no side products.
Thus, we first attempted a reaction of fac-[Re I (CO)3(bpy)Br] with an excess (2.5-5 eq.) of NOBF4 in DCM. During the course of the reaction, the colour of the solution changed from a dark to a pale yellow and the same lost its photoluminescence properties. The corresponding dicarbonyl-nitrosyl fac-[Re(CO)2(NO)(bpy)Br] + species (1) was isolated as a BF4 − salt in 70% yield (Figure 1), following crystallization by vapor diffusion with pentane or by slow evaporation of DMC, after excess NOBF4 was filtered off. In its crystalline form, 1 is slightly hygroscopic, and it decomposes if purification is attempted on a solid phase (silica or alumina). The same reaction was also attempted with phenanthroline (phen) and 4,4′-or 4,7-derivatives of bpy and phen, respectively, giving similar results (complexes 2-5, Figure 1, in 60-70% yield). In comparison to the synthetic procedures of Alberto and Berke, our route appears straightforward, overall higher yielding and generally applicable to widely accessible α-diimine fac-[Re I (CO)3] + species.

Synthesis of fac-[Re(CO) 2 (NO)(N-N)X] + Species
The chemistry of the fac-[Re(CO) 2 (NO)] 2+ core is essentially dominated by cyclopentadienyl (Cp) species of general formula [CpRe(CO) 2 (NO)] + . These compounds are most often prepared by reaction of the corresponding [CpRe(CO) 3 ] with either NO 2 PF 6 [29], NOHSO 4 [30], or NOBF 4 [31,32]. The last two reagents were successfully used in the preparation of fac-[Re I (CO) 2 (NO)X 3 ] − [24,27], and of the two, the latter appeared to us the most convenient as the procedure involves simple addition of the nitrosonium tetrafluoroborate salt in a CH 2 Cl 2 (DCM) solution of the rhenium tricarbonyl complex [32]. The reaction has also the advantage of producing an ion pair from the initially introduced components with, theoretically, no side products.
Thus, we first attempted a reaction of fac-[Re I (CO) 3 (bpy)Br] with an excess (2.5-5 eq.) of NOBF 4 in DCM. During the course of the reaction, the colour of the solution changed from a dark to a pale yellow and the same lost its photoluminescence properties. The corresponding dicarbonyl-nitrosyl fac-[Re(CO) 2 (NO)(bpy)Br] + species (1) was isolated as a BF 4 − salt in 70% yield (Figure 1), following crystallization by vapor diffusion with pentane or by slow evaporation of DMC, after excess NOBF 4 was filtered off. In its crystalline form, 1 is slightly hygroscopic, and it decomposes if purification is attempted on a solid phase (silica or alumina). The same reaction was also attempted with phenanthroline (phen) and 4,4 -or 4,7-derivatives of bpy and phen, respectively, giving similar results (complexes 2-5, Figure 1, in 60-70% yield). In comparison to the synthetic procedures of Alberto and Berke, our route appears straightforward, overall higher yielding and generally applicable to widely accessible α-diimine fac-[Re I (CO) 3 ] + species.

Spectroscopic Properties of fac-[Re(CO) 2 (NO)(N-N)X] + Species
The physical properties of the fac-[Re(CO) 2 (NO)] 2+ complexes prepared in this study are summarized in Table 1. The IR spectra of the compounds show the pattern expected for the dicarbonyl-nitrosyl species. Consistent with what reported before, the CO stretching (νCO's) frequencies of fac-[Re(CO) 2 (NO)(N-N)Br] + complexes 1-5 are substantially shifted to higher wavenumbers, which is unusual for carbonyls bound to the low valent metal [33,34]. In fact, the νCO's are found in the region where rhenium(III) dicarbonyl complexes [35] (e.g., [Re III (CO) 2 Br 4 ] − ) [36] are observed, and much higher than corresponding rhenium(II) species [37]. The symmetric νCO mode of the molecules is actually not far from that of CO gas (2143 cm −1 ). The evidence points to a significant reduction of Re-CO π-backbonding in favour of the stronger π-acceptor NO + . The stretching vibration of the NO + ion usually occurs in the 2300-2350 cm −1 frequency range, e.g., 2340 cm −1 in NOBF 4 [38], 2326 cm −1 in NOAuF 6 [39], and 2298 cm −1 in sulfuric acid solutions [40]. Its vibrational frequency in the complexes is found in the 1800 cm −1 region, closer to that of a N=O double bond than that of the initial triple bond. This indicates that the π*p(NO)-orbitals accept electron density to a great degree, depleting the metal ion of the same. Theoretically, a N=O double implies full occupation of a π*p(NO)-orbital, which would formally result in a metal center of higher oxidation state. Indeed, this formalism could account for the reactivity of the species (vide infra) and their lack of photoluminescence (see Supplementary Materials).

Spectroscopic Properties of fac-[Re(CO)2(NO)(N-N)X] + Species
The physical properties of the fac-[Re(CO)2(NO)] 2+ complexes prepared in this study are summarized in Table 1. The IR spectra of the compounds show the pattern expected for the dicarbonyl-nitrosyl species. Consistent with what reported before, the CO stretching (νCO's) frequencies of fac-[Re(CO)2(NO)(N-N)Br] + complexes 1-5 are substantially shifted to higher wavenumbers, which is unusual for carbonyls bound to the low valent metal [33,34]. In fact, the νCO's are found in the region where rhenium(III) dicarbonyl complexes [35] (e.g., [Re III (CO)2Br4] − ) [36] are observed, and much higher than corresponding rhenium(II) species [37]. The symmetric νCO mode of the molecules is actually not far from that of CO gas (2143 cm −1 ). The evidence points to a significant reduction of Re-CO π-backbonding in favour of the stronger π-acceptor NO + . The stretching vibration of the NO + ion usually occurs in the 2300-2350 cm −1 frequency range, e.g., 2340 cm −1 in NOBF4 [38], 2326 cm −1 in NOAuF6 [39], and 2298 cm −1 in sulfuric acid solutions [40]. Its vibrational frequency in the complexes is found in the 1800 cm −1 region, closer to that of a N=O double bond than that of the initial triple bond. This indicates that the π*p(NO)-orbitals accept electron density to a great degree, depleting the metal ion of the same. Theoretically, a N=O double implies full occupation of a π*p(NO)-orbital, which would formally result in a metal center of higher oxidation state. Indeed, this formalism could account for the reactivity of the species (vide infra) and their lack of photoluminescence (see Supplementary Materials).  The UV-Vis spectra of the compounds are characterized by a main absorption with two closely spaced maxima in 300-340 nm region (Table 1 and Supplementary Materials). Only complexes 2 and 5 (phenanthroline derivatives) show a single relatively broad peak for the same absorption, with two additional lower-lying small peaks at 340 and 375 nm, respectively. We did not perform a TDDFT analysis, but we suggest that the high-energy transitions are likely associated with π → π* intra-ligand transitions attributed to the diimine-system. In solution, all dicarbonyl-nitrosyl species show sharp signals in their NMR spectra, consistent with the diamagnetic nature of the molecules. With respect to the corresponding tricarbonyl complexes, fac-[Re(CO) 2 (NO)(N-N)X] + show consistently a downfield shift of the N-N signals ( Figure 2 and Supplementary Materials). This evidence further supports the assignment of a higher oxidation state of the Re atom.
Solid state pure product. in DMF.
The UV-Vis spectra of the compounds are characterized by a main absorption with two closely spaced maxima in 300-340 nm region (Table 1 and Supplementary Materials). Only complexes 2 and 5 (phenanthroline derivatives) show a single relatively broad peak for the same absorption, with two additional lower-lying small peaks at 340 and 375 nm, respectively. We did not perform a TDDFT analysis, but we suggest that the high-energy transitions are likely associated with π → π* intra-ligand transitions attributed to the diimine-system. In solution, all dicarbonyl-nitrosyl species show sharp signals in their NMR spectra, consistent with the diamagnetic nature of the molecules. With respect to the corresponding tricarbonyl complexes, fac-[Re(CO)2(NO)(N-N)X] + show consistently a downfield shift of the N-N signals ( Figure 2 and Supplementary Materials). This evidence further supports the assignment of a higher oxidation state of the Re atom.

Attempted Synthesis of fac-[Re(CO)2(NO)(N-N)L] 2+ Species
Having established a sufficiently high-yielding procedure for fac-[Re(CO)2(NO)(N-N)Br] + ions, we moved to explore the substitution of Br − for neutral pyridine (py) ligands. Typically, for the corresponding tricarbonyl complexes, bromide replacement is achieved either by treatment with trifluoromethanesulfonic acid or by addition of a silver salt. We first monitored by 1 H-NMR the addition of AgCF3SO3 to fac-[Re(CO)2(NO)(bpy)Br] + (1) in coordinating wet solvents like CH3OH or CH3CN. The spectrum revealed no change in the frequency of the proton signals over a period of 3 days. In a parallel reaction, the same conditions were used, but pyridine was added to the mixture. Overnight, new signals appeared in the NMR spectrum, but the set of frequencies attributable to free py remained

Attempted Synthesis of fac-[Re(CO) 2 (NO)(N-N)L] 2+ Species
Having established a sufficiently high-yielding procedure for fac-[Re(CO) 2 (NO)(N-N)Br] + ions, we moved to explore the substitution of Br − for neutral pyridine (py) ligands. Typically, for the corresponding tricarbonyl complexes, bromide replacement is achieved either by treatment with trifluoromethanesulfonic acid or by addition of a silver salt. We first monitored by 1 H-NMR the addition of AgCF 3 SO 3 to fac-[Re(CO) 2 (NO)(bpy)Br] + (1) in coordinating wet solvents like CH 3 OH or CH 3 CN. The spectrum revealed no change in the frequency of the proton signals over a period of 3 days. In a parallel reaction, the same conditions were used, but pyridine was added to the mixture. Overnight, new signals appeared in the NMR spectrum, but the set of frequencies attributable to free py remained unchanged. We initially hypothesized that the hydroxide fac-[Re(CO) 2 (NO)(bpy)(OH)] + had formed, but later found that py, as a base, promoted BF 4 − hydrolysis to [BF 3 (OH)] − and F − [41], and the latter substituted Br − to give fac-[Re(CO) 2 (NO)(bpy)F] + (6, Figure 3). As mentioned above, this type of reactivity of the metal ion is consistent with a hard Re acid and fully congruous with the spectroscopic data discussed above.
The higher apparent formal oxidation state of the metal ion implies the depletion of electron density from the same, and affinity for π-basic ligands rater σ-donors. We reasoned, therefore, that electron-donating substituents on N-N might help stabilize the rhenium ion towards the same reaction. NR 2 groups (where R = aliphatic chain) are amongst the most effective electron donating groups [42]. However, when the N 4 ,N 4 ,N 4 ,N 4tetraethyl-[2,2 -bipyridine]-4,4 -diamine (Et 2 N-bpy) complex 3 was used the corresponding fac-[Re I (CO) 2 (NO)(Et 2 N-bpy)F] + (7) also formed as the only product. Compound (7) was isolated in 30% yield and was recrystallized from methanol. Its X-ray structure is also shown in Figure 3.
We recently published synthetic procedures to aerobically stable and substitutionally labile α-diimine rhenium(I) dicarbonyl complexes of formula [Re I (CO) 2 (N-N)Br(py)] capable of exchanging the halide for other ligands [37]. Therefore, we next tried the reaction of the corresponding [Re I (CO) 2 (bpy)Br(py)] complex (8) with NOBF 4 . Under reaction conditions similar to those applied for the synthesis of 1-5, complex 8 reacted by substituting py for NO + giving 1 (Figure 4). We only found trace evidence in the MS spectrum of the desired fac-[Re(CO) 2 (NO)(bpy)py] 2+ species. unchanged. We initially hypothesized that the hydroxide fac-[Re(CO)2(NO)(bpy)(OH)] + had formed, but later found that py, as a base, promoted BF4 − hydrolysis to [BF3(OH)] − and F − [41], and the latter substituted Brto give fac-[Re(CO)2(NO)(bpy)F] + (6, Figure 3). As mentioned above, this type of reactivity of the metal ion is consistent with a hard Re acid and fully congruous with the spectroscopic data discussed above. The higher apparent formal oxidation state of the metal ion implies the depletion of electron density from the same, and affinity for π-basic ligands rater σ-donors. We reasoned, therefore, that electron-donating substituents on N-N might help stabilize the rhenium ion towards the same reaction. NR2 groups (where R = aliphatic chain) are amongst the most effective electron donating groups [42]. However, when the N 4 ,N 4 ,N 4′ ,N 4′ -tetraethyl-[2,2′-bipyridine]-4,4′-diamine (Et2N-bpy) complex 3 was used the corresponding fac-[Re I (CO)2(NO)(Et2N-bpy)F] + (7) also formed as the only product. Compound (7) was isolated in 30% yield and was recrystallized from methanol. Its X-ray structure is also shown in Figure 3.
We recently published synthetic procedures to aerobically stable and substitutionally labile α-diimine rhenium(I) dicarbonyl complexes of formula [Re I (CO)2(N-N)Br(py)] capable of exchanging the halide for other ligands [37]. Therefore, we next tried the reaction of the corresponding [Re I (CO)2(bpy)Br(py)] complex (8) with NOBF4. Under reaction conditions similar to those applied for the synthesis of 1-5, complex 8 reacted by substituting py for NO + giving 1 (Figure 4). We only found trace evidence in the MS spectrum of the desired fac-[Re(CO)2(NO)(bpy)py] 2+ species.  It should be noted here that Rattat reported that whereas the imidazole (Im) complexes [ReCl2(Im)(CO)2(NO)] and [ReCl(Im)2(CO)2(NO)] + can be synthesized in high yields from [NEt4][ReCl3(CO)2(NO)] or [ReCl(μ-Cl)(CO)2(NO)]2, isolation of the [Re(Im)3(CO)2(NO)] 2+ was not successful [43]. The authors argued that this is due to the behaviour of the fac-[Re(CO)2(NO)] 2+ fragment in water (the reaction solvent), where the core initially binds three water molecules, one of which is deprotonated, and the resulting hydroxy group cannot be substituted by the σ-donor Im [44]. However, the trace evidence of the desired fac-[Re(CO)2(NO)(bpy)py] 2+ species we detected by mass spectrometry, encouraged us to pursue our attempts.
Therefore, we probed directly the reactivity of fac-[Re I (CO) 3 (N-N)(py)] + complexes with nitrosonium tetrafluoroborate. Following the logic above, we probed the reaction of fac-[Re(CO) 3 ] + complexes with combinations of bpy and Et 2 N-bpy (as N-N ligands) with py and N,N-dimethylpyridin-4-amine (Me 2 N-py) [45,46]. What guided our choice, was again consideration that electron-donating substituents (EDS) on N-N or py might be needed to stabilize the rhenium ion in the particular ligand arrangement. We envisioned two cases as shown in Figure 5. In case A we considered the possibility of EDS on the bidentate N-N ligand cis to NO, in case B EDS on the monodentate ligand trans to NO. As illustrated in Figure 5, we found no evidence of reaction with NO + when the fac-[Re I (CO) 3 (Et 2 N-bpy)(py)] + complex A was tested. However, complex B gave the corresponding fac-[Re(CO) 2 (NO)(bpy)(Me 2 N-py)] 2+ (9) species as the kinetic, but not as the thermodynamically stable, product. The dicationic species could be isolated as it precipitated immediately from DCM following CO replacement by NO + . Evidence for the product came from both NMR and IR, which show, respectively, the expected downfield shift of all protons and the dicarbonyl-nitrosyl pattern (Supplementary Materials). The complex, however, is not pure and purification or crystallization attempts invariably lead to its decomposition.

Reactivity of fac-[Re I (CO)3(N-N)OR] Species (OR = π-base) with NO +
While studying the reactions above, and in order to better understand the chemistry of the NO + species, we also decided to explore nitrosylation of fac-[Re I (CO)3(N-N)] complexes with monodentate π-basic ligands (OR). Given the apparent affinity of the fac-[Re(CO)2(NO)] 2+ core for π-donors, we reasoned that fac-[Re I (CO)3(N-N)OR] species might offer us a different chemical approach for the design of an efficient synthetic strategy to fac-[Re(CO)2(NO)(N-N)L] 2+ compounds. Therefore, we decided to test the reaction of fac-[Re I (CO)3(N-N)OR], where OR = OH − , benzoate (10), 2-(4-bromophenyl)acetate (11).
To our surprise, irrespective of the OR ligand, nitrosylation of fac-[Re I (CO)3(N-N)OR] gave always the same dicarbonyl-nitrosyl product (i.e., with the identical spectroscopic signature). In the case of OR = benzoate or 2-(4-bromophenyl)acetate, the NMR evidence clearly indicated that OR was no longer coordinated to the rhenium ion. However, it was initially difficult to reconcile the spectroscopic fingerprints of the product with those of the same obtained from the hydroxo complex (i.e., when OR = OH − ), also in light of the fact that we used dry solvents in the manipulations. The relatively high νCO frequencies of the product (2127 and 2069 cm −1 ) were also surprising and, on the basis of what we have shown before [33,34], they could not correspond to the electronic contribution of a coordinated OH − base. Kurz

Reactivity of fac-[Re I (CO) 3 (N-N)OR] Species (OR = π-Base) with NO +
While studying the reactions above, and in order to better understand the chemistry of the NO + species, we also decided to explore nitrosylation of fac-[Re I (CO) 3 (N-N)] complexes with monodentate π-basic ligands (OR). Given the apparent affinity of the fac-[Re(CO) 2 (NO)] 2+ core for π-donors, we reasoned that fac-[Re I (CO) 3 (N-N)OR] species might offer us a different chemical approach for the design of an efficient synthetic strategy to fac-[Re(CO) 2 (NO)(N-N)L] 2+ compounds. Therefore, we decided to test the reaction of fac-[Re I (CO) 3 (N-N)OR], where OR = OH − , benzoate (10), 2-(4-bromophenyl)acetate (11).
To our surprise, irrespective of the OR ligand, nitrosylation of fac-[Re I (CO) 3 (N-N)OR] gave always the same dicarbonyl-nitrosyl product (i.e., with the identical spectroscopic signature). In the case of OR = benzoate or 2-(4-bromophenyl)acetate, the NMR evidence clearly indicated that OR was no longer coordinated to the rhenium ion. However, it was initially difficult to reconcile the spectroscopic fingerprints of the product with those of the same obtained from the hydroxo complex (i.e., when OR = OH − ), also in light of the fact that we used dry solvents in the manipulations. The relatively high νCO frequencies of the product (2127 and 2069 cm −1 ) were also surprising and, on the basis of what we have shown before [33,34], they could not correspond to the electronic contribution of a coordinated OH − base. Kurz and Alberto showed that the reactivity µ-oxo bridged teranuclear [Re(µ 3 -O)(CO) 2 (NO)] 4 clusters towards neutral bidentate ligands is possible by disassembly of the same in HBF 4 and proceeds "presumably [via] Re-bound labile BF 4 − anion" [27]. We managed to crystallize the nitrosylated product obtained from fac-[Re I (CO) 3 (N-N)OR] and we confirmed that the reaction gives fac-[Re(CO) 2 (NO)(N-N)(BF 4 )][BF 4 ] (12) as the only product in good yield ( Figure 6). To our knowledge, 12 is only the fourth structurally characterized Re-FBF 3 complex, and the very first one of its kind [47][48][49]. The Re-FBF 3 bond is persistent in solution, and in CH 3 CN only a small fraction of the molecules (ca. 5-7%) substitute the anion for CH 3 CN. We were also able to selectively crystallize out the fac-[Re(CO) 2 (NO)(N-N)(CH 3 CN)] 2+ complex (13) as a [Na(BF 4 ) 3 ] 2salt ( Figure 6), but we did not study it further.

X-ray Crystallography
Crystallographic

X-ray Crystallography
Crystallographic details of all complexes reported here are in Supplementary Materials, while selected bond lengths of fac-[Re(CO) 2 (NO)] 2+ species are given in figure captions. All rhenium dicarbonyl-nitrosyl complexes show a distorted octahedral geometry around the Re ion. Structural analysis of the species and comparison to related fac-[Re(CO) 3 ] + species, revealed the following general characteristics. Within 3σ, the Re-CO and the C≡O bonds are respectively longer and shorter than the corresponding tricarbonyl complexes. There is no significant statistical difference in the Re-Br bond, while the Re-N(diamine) is slightly shorter in fac-[Re(CO) 2 (NO)] 2+ species. In these, overall, crystal parameters are consistent with a rhenium ion in a higher oxidation state than +1 and are in agreement with the spectroscopic data. The shorter C≡O distances, e.g., are clearly reflected in the higher frequency of vibration of the bond in the IR spectrum. Likewise, the longer N-O distance (by ca. 0.1 Å in comparison to the free ion [50,51]) of Re-bound NO is observed in a lower frequency vibration of the same. Perhaps the most striking feature in fac-[Re(CO) 2 (NO)(N-N)Br] + species (1)(2)(3)(4)(5) is represented by the bending (ca. 17 • , but up to 25 • for complex 7) of the diamine ligand away from the bound NO (the diimine and the Re(CO) 2 planes define the angle). In comparison, the same angle measures 4-6 • in corresponding tricarbonyl molecules, and ca. 11 • for 12 and 13. Similarly, in nitrosyl complexes 1-5, the two COs are also slightly bent towards the same direction ( Figure 7). Overall, the molecules appear to be moving towards a trigonal distortion observed in octahedral d 4 complexes [52].

CO Releasing Properties
In the initial phases of our investigation, we also probed the direct nitrosylation of tricarbonyl complexes with ortho-substituted α-diimines. The reaction is generally lower yielding with these ligands, but it works as well. In synthetic terms, nitrosylation of the complex bearing 6-methyl-2,2′-bipyridine (6Me-bpy) gave the best results (67% yield). We found, however, that when CH3CN solutions of fac-[Re(CO)2(NO)(6Me-bpy)Br]BF4 (14) were left exposed to ambient light, over time, crystals of the fully oxidized perrhenate ion appeared (Figure 8).

CO Releasing Properties
In the initial phases of our investigation, we also probed the direct nitrosylation of tricarbonyl complexes with ortho-substituted α-diimines. The reaction is generally lower yielding with these ligands, but it works as well. In synthetic terms, nitrosylation of the complex bearing 6-methyl-2,2 -bipyridine (6Me-bpy) gave the best results (67% yield). We found, however, that when CH 3 CN solutions of fac-[Re(CO) 2 (NO)(6Me-bpy)Br]BF 4 (14) were left exposed to ambient light, over time, crystals of the fully oxidized perrhenate ion appeared (Figure 8).
tricarbonyl complexes with ortho-substituted α-diimines. The reaction is generally lower yielding with these ligands, but it works as well. In synthetic terms, nitrosylation of the complex bearing 6-methyl-2,2′-bipyridine (6Me-bpy) gave the best results (67% yield). We found, however, that when CH3CN solutions of fac-[Re(CO)2(NO)(6Me-bpy)Br]BF4 (14) were left exposed to ambient light, over time, crystals of the fully oxidized perrhenate ion appeared (Figure 8).  Spectrophotometric measurements of the CO release from complexes 1-5 and 14, as a function of the conversion of deoxy-Mb to MbCO, revealed that dicarbonyl-mononitrosyl complexes only released the gas if exposed to a cold light source of 275-375 nm radiation. In the dark, the complexes are stable and do not elicit any change in the deoxy-Mb spectrum. A typical spectrum of the conversion of the deoxy-Mb spectrum under photolysis of 1-5 and 14 is given in Figure 9. The equivalents of CO released by the molecules were calculated by measuring the change of absorbance at 540 nm (ε 540 = 15.4 mmol L −1 cm −1 ), as a direct measure of the concentration of MbCO. The amount of the formed MbCO is dependent on the concentration of the complex, but analysis of the saturation curve of MbCO showed, that for all tested complexes approximately 0.6-0.7 moles CO are released per mole of complex. In Figure 9, the peak at 620 nm is attributable to the formation of metmyoglobin (MetMb) after prolonged exposure to the light source [54]. The loss of CO was verified by MS experiments, whereby solutions of the complexes were irradiated under similar conditions in CH 3 CN solutions. The spectra consistently revealed that only CO is released by the species during the irradiation process and that a solvent molecule replaces the ligand.
To our knowledge, fac-[Re(CO) 2 (NO)(N-N)Br] + complexes represent a new class of Re photoCORMs. Spontaneous and light-induced CO release of 16-and 17-electron rhenium complexes [55][56][57], and 18-electron fac-[Re I (CO) 3 (N-N)PR 3 ] + (where PR 3 = phosphine or phosphite) is well known [58][59][60]. In the last five years several examples of diimine complexes bearing either σor π-donating ancillary ligands active towards CO photosubstitution have also been described [61][62][63][64][65]. For PR 3 species, the strong trans-labilizing ability of the phosphorus donor of π-acid ligands is crucial for activating Re tricarbonyl species towards photochemical substitution of CO, and works in conjunction with the internal conversion between the 3 MLCT and thermally accessible higher energy photoexcited 3 LF state that is productive in terms of CO dissociation [66]. For tricarbonyl rhenium diimine complexes with π-basic ligands, mechanistic studies and picosecond time-resolved IR measurements indicate that only irradiation with higher energy photons can induce photochemical ligand substitution reactions via higher energy vibrational states rather than the lowest-lying 3 MLCT excited or thermally accessible 3 LF states. These higher vibrational levels are those of the 1 MLCT state and/or higher electronic excited state(s) including the Re → CO 1 MLCT transition. Thus, excitation by high-energy light of fac-[Re(CO) 3 (N-N)(L)] n species (were L = π-base or σ-donor ligand), leads to vibrationally hot photoproducts, which relax within 50−100 ps, while CO ligand dissociation occurs with subpicosecond rates after excitation [67]. A similar mechanism is likely to be at play here. nm radiation. In the dark, the complexes are stable and do not elicit any change in the deoxy-Mb spectrum. A typical spectrum of the conversion of the deoxy-Mb spectrum under photolysis of 1-5 and 14 is given in Figure 9. The equivalents of CO released by the molecules were calculated by measuring the change of absorbance at 540 nm (ε540 = 15.4 mmol L −1 cm −1 ), as a direct measure of the concentration of MbCO. The amount of the formed MbCO is dependent on the concentration of the complex, but analysis of the saturation curve of MbCO showed, that for all tested complexes approximately 0.6-0.7 moles CO are released per mole of complex. In Figure 9, the peak at 620 nm is attributable to the formation of metmyoglobin (MetMb) after prolonged exposure to the light source [54]. The loss of CO was verified by MS experiments, whereby solutions of the complexes were irradiated under similar conditions in CH3CN solutions. The spectra consistently revealed that only CO is released by the species during the irradiation process and that a solvent molecule replaces the ligand.  buffer at pH 6.8) were exposed to a 275 nm light source (intervals of 10 min) before the conversion reached a plateau after 120 min. Prolonged exposure to the light source eventually favoured formation of metmyoglobin (MetMb), as evidenced by the peak at 620 nm. In the reaction scheme above the spectra, S = solvent molecule.

Antimicrobial Properties of Selected Complexes
As mentioned in the introduction, this study was initiated aiming at the synthesis of structurally nearly identical higher charge congeners of active antimicrobial rhenium tricarbonyl complexes. Our previous reports on those species indicate that neutral fac-

Reagents and Chemicals
All reagent and solvents were purchased from standard sources and used without further purification. Compound [Re(CO) 5  were synthesized according to published procedures. Unless otherwise noted, solvents used in the preparation of all molecules were dry and O 2 -free.

Instruments and Analysis
NMR spectra were measured on a Bruker Advance III 400 MHz. The corresponding 1 H chemical shifts are reported relative to residual solvent protons. Mass analyses were performed using a Bruker FTMS 4.7-T Apex II in positive mode. UV-Vis spectra were measured on a Jasco V730 spectrophotometer. IR spectra were recorded on a Bruker TENSOR II with the following parameters: 16 scans for background, 32 scans for sample with a resolution of 4 cm −1 in the 4000-600 cm −1 region. Single crystal diffraction data collection was performed on a Stoe IPDS2 diffractometer (CuKα1 (λ = 1.5406 Å)) equipped with a cryostat from Oxford Cryosystems. The structures were solved with the ShelXT structure solution program using Intrinsic Phasing and refined with the ShelXL refinement package using Least Squares minimization [69,70]. All crystal structures are deposited at the Cambridge Crystallographic Data Centre. CCDC numbers 2093631-2093640 and 2094070 contain the supplementary crystallographic data for this paper. These data can be obtained free of charge from the Cambridge Crystallographic Data Centre via www.ccdc. cam.ac.uk/structures (accessed on 20 July 2021).

Synthetic Procedures
The following general procedure was followed for the synthesis of [Re(CO) 2 (NO)(N-N)Br]BF 4 complexes. In a glove box the corresponding fac-[Re(CO) 3 (N-N)Br] (typically 0.2 mmol ca. 100 mg) was dissolved in CH 2 Cl 2 (100 mL, dry). To the resulting yellow solution, NOBF 4 (84-115 mg, 0.5-1 mmol, 2.5-5 eq.) was added in the solid form. The reaction was stirred at room temperature for 2 days. A light off-white precipitate was filtered off and the filtrate either allowed to evaporate or layered with pentane to afford light yellow crystals, which were collected by filtration.

[Re(CO) 2 NO(ϕ-phen)Br](BF 4 ) (5). ϕ-phen
[Re(CO) 2 (NO)(bpy)F](BF 4 ) (6). Complex 1 (50.7 mg) was dissolved in methanol (5 mL) and the solution was heated to 55 • C. Pyridine (20.2 mg) and silver triflate (33 mg) were added in the dark. The mixture was stirred at 55 • C overnight. After filtration, the filtrate was dried under reduced pressure. The crude product was then dissolved in a minimal amount of methanol and precipitated with cold diethylether to give 6 as a white/pale yellow solid (11.4  The fac-[Re(CO) 3 (bpy)] carboxylato complexes were prepared by adaptation of a published procedure [71]. Briefly, fac-[Re(CO) 3 (bpy)Br] (100 mg, 0.2 mmol) and the appropriate carboxylic acid ligand were dissolved in anhydrous degassed tetrahydrofuran (30 mL). The reaction mixture was stirred for 5 min, then trimethylamine (33 µL, 24 mg, 0.24 mmol) and AgCF 3 SO 3 (50 mg, 0.2 mmol) were added, and the mixture stirred at 70 • C for 18 h. The mixture was filtered, solvent evaporated to dryness and the residue purified by column chromatography on deactivated alumina with DCM as the eluent. Analytically pure products were obtained after recrystallization from dichloromethane/n-hexane mixtures.

Detection of CO Release Using the Myoglobin Assay
The photorelease of CO from 1-5 and 13 was assessed spectrophotometrically by measuring the conversion of deoxymyoglobin (Mb) to carbonmonoxy myoglobin (MbCO) as previously reported [72]. A small aliquot of a freshly prepared solution of the selected complex (in DMSO) was added to 1 mL of the Mb solution in phosphate buffer (0.05 M) prepared at pH 6. 8. Final concentrations: 20 µM for Re complex and Mb. Mb spectra were recorded after each photoirradiation (5-10 min) at 375nm at 25 • C. The methanol or DMSO content of the solution never exceeded 0.5%. The amount of MbCO formed was determined by measuring the absorbance at 540 nm (extinction coefficient ε = 15.4 M cm −1 ). The MbCO concentration was plotted over time and directly related to the equivalents of CO released from the compounds. Control experiments were run under identical conditions but without light or the addition of the metal complexes.

Strains and Culture Conditions
The antimicrobial activity of selected [Re(CO) 2 (NO)(N-N)X]BF 4 was evaluated against 8 different microorganisms including four Gram-negative bacteria (Enterobacter cloaceae ATCC 3047, Klebsiella pneumoniae ATCC 13803, Acinetobacter baumanii ATCC 19606, Pseudomonas aeruginosa PAO1 NCTC10332), two Gram-positive bacteria (Staphylococcus aureus MRSA43300 (methicillin-resistant) and S. aureus ATCC25923 (methicillin-sensitive)) and two fungi (Candida albicans SC5314) and C. auris (a clinical strain)). All reference strains were obtained from the American Type Culture Collection (ATCC) and the National Collection of Type Cultures (NCTC), while the clinical C. auris strain 7 was kindly provided by Dr Aleksandra Barac (University Clinical Center of Serbia) and Prof. Cornelia Lass-Floerl (University of Innsbruck). Prior to each experiment, frozen stocks in 20% glycerol at −80 • C were thawed and inoculated onto solid Yeast-Potato Dextose (YPD) plates (fungi) or Lauria (LA) agar plates (bacteria), and cultured at 37 • C for 24-48 h.

In Vitro Antimicrobial Activity Determination
Antimicrobial activity was addressed by determining the minimum inhibitory concentration (MIC) of the tested complexes according to the standard broth microdilution assays, recommended by CLSI (the Clinical and Laboratory Standards Institute; M07-A10. CLSI) and EUCAST (European Committee on Antimicrobial Susceptibility Testing; EUCAST antifungal MIC method for yeasts, v 7.3.1). The test strains grown in YPD (fungi) and LA (bacteria) were diluted in RPMI 1640 medium with 2% glucose (Gibco) and Luria-Bertani broth (Biolife Italiana S.r.l., Milano, Italy) to give the concentration of 1 × 105 CFU/mL cells (for fungi) and 5 × 105 CFU/mL (for bacteria), respectively. The MIC assay was performed in 96-well microtiter plates (Sarstedt, Germany) by making serial twofold dilutions of the tested substances in appropriate liquid media to give the volume of 100 µL. The media solution with microorganisms was dispensed to each well to make the final volume of 200 µL. All complexes were tested in the concentrations range from 100 to 3.13 µM. After incubation at 37 • C for 18-24 h without shaking, the growth of tested microorganisms was determined measuring absorbance at 530 nm (fungi) and 600 nm (bacteria) using a Tecan Infinite 200 Pro multiplate reader (Tecan Group Ltd., Männedorf, Switzerland). The negative control (media only) and positive control (only microorganisms) on the same plate were used as references to determine the growth inhibition. Samples with inhibition values above 90% were classified as active agents.

Conclusions
In this contribution, we have described an efficient direct nitrosylation of α-diimine rhenium tricarbonyl complexes widely applicable to different supporting N-N ligands and studied the substitution chemistry of the resulting species. We showed that fac-[Re I (CO) 3 (N-N)Br] complexes react efficiently with NOBF 4 to yield the corresponding dicarbonyl-mononitrosyl species. The resulting compounds are structurally nearly identical higher charge congeners of tricarbonyls. Although the rhenium ion is formally described as having oxidation state +1, we found that the substitution chemistry of metal ion in fac-[Re(CO) 2 (NO)(N-N)X] + is closer to that of a harder Re acid, probably due to the stronger π-acceptor properties of NO + as compared to those of CO. In comparison to tricarbonyl species, the higher apparent formal oxidation state of the metal ion in dicarbonyl-mononitrosyl complexes, implies the greater depletion of electron density from the same and, consequently, lower π-back Re-CO bonding. A fundamental consequence is that fac-[Re(CO) 2

Data Availability Statement:
The data presented in this study are available on request from the corresponding author.