Adding Diversity to a Diruthenium Biscyclopentadienyl Scaffold via Alkyne Incorporation: Synthesis and Biological Studies.

We report the synthesis and the assessment of the anticancer potential of two series of diruthenium biscyclopentadienyl carbonyl complexes. Novel dimetallacyclopentenone compounds (2-4) were obtained (45-92% yields) from the thermal reaction (PhCCPh exchange) of [Ru2Cp2(CO)(µ-CO){µ-η1:η3-C(Ph)═C(Ph)C(═O)}], 1, with alkynes HCCR [R = C5H4FeCp (Fc), 3-C6H4(Asp), 2-naphthyl; Cp = η5-C5H5, Asp = OC(O)-2-C6H4C(O)Me]. Protonation of 1-3 by HBF4 afforded the corresponding µ-alkenyl derivatives 5-7, in 40-86% yields. All products were characterized by IR and NMR spectroscopy; moreover, cyclic voltammetry (1, 2, 5, 7) and single-crystal X-ray diffraction (5, 7) analyses were performed on representative compounds. Complexes 5-7 revealed a cytotoxic activity comparable to that of cisplatin in A549 (lung adenocarcinoma), SW480 (colon adenocarcinoma), and ovarian (A2780) cancer cell lines, and 2, 5, 6, and 7 overcame cisplatin resistance in A2780cis cells. Complexes 2, 5, and 7 (but not the aspirin derivative 6) induced an increase in intracellular ROS levels. Otherwise, 6 strongly stabilizes and elongates natural DNA (from calf thymus, CT-DNA), suggesting a possible intercalation binding mode, whereas 5 is less effective in binding CT-DNA, and 7 is ineffective. This trend is reversed concerning RNA, and in particular, 7 is able to bind poly(rA)poly(rU) showing selectivity for this nucleic acid. Complexes 5-7 can interact with the albumin protein with a thermodynamic signature dominated by hydrophobic interactions. Overall, we show that organometallic species based on the Ru2Cp2(CO)x scaffold (x = 2, 3) are active against cancer cells, with different incorporated fragments influencing the interactions with nucleic acids and the production of ROS.

Anticancer Potential of Diruthenium Complexes with Bridging Hydrocarbyl Ligands from Bioactive Alkynols.

Diruthenacyclopentenone complexes of the general composition [Ru2Cp2(CO)2{µ-η1:η3-CH═C(C(OH)(R))C(═O)}] (2a-c; Cp = η5-C5H5) were synthesized in 94-96% yields from the reactions of [Ru2Cp2(CO)2{µ-η1:η3-C(Ph)═C(Ph)C(═O)}] (1) with 1-ethynylcyclopentanol, 17α-ethynylestradiol, and 17-ethynyltestosterone, respectively, in toluene at reflux. Protonation of 2a-c by HBF4 afforded the corresponding allenyl derivatives [Ru2Cp2(CO)3{µ-η1:η2-CH═C═R}]BF4 (3a-c) in 85-93% yields. All products were thoroughly characterized by elemental analysis, mass spectrometry, and IR, UV-vis, and nuclear magnetic resonance spectroscopy. Additionally, 2a and 3a were investigated by cyclic voltammetry, and the single-crystal diffraction method was employed to establish the X-ray structures of 2b and 3a. The cytotoxicity in vitro of 2b and 3a-c was evaluated against nine human cancer cell lines (A2780, A2780R, MCF-7, HOS, A549, PANC-1, Caco-2, PC-3, and HeLa), while the selectivity was assessed on normal human lung fibroblast (MRC-5). Overall, complexes exert stronger cytotoxicity than cisplatin, and 3b (comprising 17α-estradiol derived ligand) emerged as the best-performing complex. Inductively coupled plasma mass spectrometry cellular uptake studies in A2780 cells revealed a higher level of internalization for 3b and 3c compared to 2b, 3a, and the reference compound RAPTA-C. Experiments conducted on A2780 cells demonstrated a noteworthy impact of 3a and 3b on the cell cycle, leading to the majority of the cells being arrested in the G0/G1 phase. Moreover, 3a moderately induced apoptosis and oxidative stress, while 3b triggered autophagy and mitochondrial membrane potential depletion.

Diiron Aminocarbyne Complexes with NCE- Ligands (E = O, S, Se).

Diiron µ-aminocarbyne complexes [Fe2Cp2(NCMe)(CO)(µ-CO){µ-CN(Me)(R)}]CF3SO3 (R = Xyl, [1aNCMe]CF3SO3; R = Me, [1bNCMe]CF3SO3; R = Cy, [1cNCMe]CF3SO3; R = CH2Ph, [1dNCMe]CF3SO3), freshly prepared from tricarbonyl precursors [1a-d]CF3SO3, reacted with NaOCN (in acetone) and NBu4SCN (in dichloromethane) to give [Fe2Cp2(kN-NCO)(CO)(µ-CO){µ-CN(Me)(R)}] (R = Xyl, 2a; Me, 2b; Cy, 2c) and [Fe2Cp2(kN-NCS)(CO)(µ-CO){µ-CN(Me)(CH2Ph)}], 3 in 67-81% yields via substitution of the acetonitrile ligand. The reaction of [1aNCMe-1cNCMe]CF3SO3 with KSeCN in THF at reflux temperature led to the cyanide complexes [Fe2Cp2(CN)(CO)(µ-CO){µ-CNMe(R)}], 6a-c (45-67%). When the reaction of [1aNCMe]CF3SO3 with KSeCN was performed in acetone at room temperature, subsequent careful chromatography allowed the separation of moderate amounts of [Fe2Cp2(kSe-SeCN)(CO)(µ-CO){µ-CN(Me)(Xyl)}], 4a, and [Fe2Cp2(kN-NCSe)(CO)(µ-CO){µ-CN(Me)(Xyl)}], 5a. All products were fully characterized by elemental analysis, IR, and multinuclear NMR spectroscopy; moreover, the molecular structure of trans-6b was ascertained by single crystal X-ray diffraction. DFT calculations were carried out to shed light on the coordination mode and stability of the {NCSe-} fragment.

Diethylammonium iodide as catalyst for the metal-free synthesis of 5-aryl-2-oxazolidinones from aziridines and carbon dioxide.

The catalytic potential of ammonium halide salts was explored in the coupling reaction of a model aziridine with carbon dioxide, highlighting the superior activity of [NH2Et2]I. Then, working at room temperature, atmospheric CO2 pressure and in the absence of solvent, the [NH2Et2]I-catalyzed synthesis of a series of 5-aryl-2-oxazolidinones was accomplished in good to high yields and excellent selectivity, from 2-aryl-aziridines with N-methyl or N-ethyl groups. NMR studies and DFT calculations outlined the pivotal role of both the diethylammonium cation and the iodide anion. The proposed method represents a convenient choice for obtaining a limited number of valuable molecules for which more complex and more expensive catalytic systems have been reported even in recent years.

A Comprehensive Analysis of the Metal-Nitrile Bonding in an Organo-Diiron System.

Nitriles (N≡CR) are ubiquitous in coordination chemistry, yet literature studies on metal-nitrile bonding based on a multi-technique approach are rare. We selected an easily-available di-organoiron framework, containing both π-acceptor (CO, aminocarbyne) and donor (Cp = η5-C5H5) ligands, as a suitable system to provide a comprehensive description of the iron-nitrile bond. Thus, the new nitrile (2-12)CF3SO3 and the related imine/amine complexes (8-9)CF3SO3 were synthesized in 58-83% yields from the respective tris-carbonyl precursors (1a-d)CF3SO3, using the TMNO strategy (TMNO = trimethylamine-N-oxide). The products were fully characterized by elemental analysis, IR (solution and solid state) and multinuclear NMR spectroscopy. In addition, the structures of (2)CF3SO3, (3)CF3SO3, (5)CF3SO3 and (11)CF3SO3 were ascertained by single crystal X-ray diffraction. Salient spectroscopic data of the nitrile complexes are coherent with the scale of electron-donor power of the R substituents; otherwise, this scale does not match the degree of Fe → N π-back-donation and the Fe-N bond energies, which were elucidated in (2-7)CF3SO3 by DFT calculations.

Recent Advances in the Chemistry of Metal Carbamates.

Following a related review dating back to 2003, the present review discusses in detail the various synthetic, structural and reactivity aspects of metal species containing one or more carbamato ligands, representing a large family of compounds across all the periodic table. A preliminary overview is provided on the reactivity of carbon dioxide with amines, and emphasis is given to recent findings concerning applications in various fields.

Modifying bis(triflimide) ionic liquids by dissolving early transition metal carbamates.

The authors report the first modification of ionic liquids with metal carbamates. A selection of homoleptic N,N-dialkylcarbamates of group 4 and 5 metals, M(O2CNR2)n, were dissolved in bis(trifluoromethylsulfonyl)imide-based ionic liquids, i.e. [bmim][Tf2N] and [P(oct)4][Tf2N], at 293 K. The resulting solutions were characterized by means of IR, UV and NMR spectroscopy, and the data were compared to those of the respective metal compounds. Notably, the dissolution process did not proceed with the release of any of the original carbamato ligands, thus preserving the intact coordination frame around the metal centre. The solvation process of Ti(O2CNiPr2)4, as a model species, in [bmim][Tf2N] was rationalized by DFT calculations. As a comparative study, solutions of NbF5 and MCl5 (M = Nb, Ta) in [bmim][Tf2N] were also investigated, revealing the possible occurrence of solvent anion coordination to the metal centres.

Mixed valence triiron complexes from the conjugation of [FeIFeI] and [FeII] complexes via intermolecular carbyne/alkyne coupling.

We present a new synthetic strategy for obtaining mixed-valence triiron complexes where the metal centers are bridged by a novel, highly functionalized hydrocarbyl ligand. The alkynyl-vinyliminium complexes [Fe2Cp2(CO)(µ-CO){µ-η1:η3-C(X-CCH)CHCNMe2}]CF3SO3 (X = 4-C6H4, [2a1]CF3SO3; X = (CH2)3, [2a2]CF3SO3) were synthesized in almost quantitative yields from the aminocarbyne precursor [Fe2Cp2(CO)2(µ-CO){µ-CNMe2}]CF3SO3, [1a]CF3SO3, and the di-alkynes HCC-X-CCH. Then, the ferracycle [Fe(Cp)(CO){C(NMe2)CHC(4-C6H4CCH)C(O)}], 4a1, was produced in 47% yield from the cleavage of [2a1]CF3SO3 promoted by pyrrolidine. Subsequent reactions of the acetonitrile adducts [Fe2Cp2(CO)(µ-CO)(NCMe){µ-CNMe(R)}]CF3SO3 (R = Me, [1aACN]CF3SO3; R = Xyl, [1bACN]CF3SO3) ([FeIFeI]) with 4a1 ([FeII]) at room temperature resulted in the formation of [FeIFeIFeII] complexes [Fe2Cp2(CO)(µ-CO){µ-η1:η3-C(X-CCHC(NMe2)FeCp(CO)CO)CHCNMe(R)}]CF3SO3 (R = Me, [5a1]CF3SO3; R = Xyl, [5b1]CF3SO3) in yields ranging from 56% to 64%. The new products were characterized by IR and multinuclear NMR spectroscopy, and the structures of [2a2]CF3SO3 and 4a1 were confirmed by single crystal X-ray diffraction. Cyclic voltammetry and spectroelectrochemical studies on [5a1]+ have revealed that reduction and oxidation events occur almost independently at the [FeIFeI] and [FeII] units, respectively. This observation underscores a minimal electronic interaction between the two fragments within the triiron complex. Accordingly, DFT studies pointed out that the HOMO and LUMO orbitals are predominantly localized in the two distinct compartments of [5a1]+.

The choice of µ-vinyliminium ligand substituents is key to optimize the antiproliferative activity of related diiron complexes.

Diiron vinyliminium complexes constitute a large family of organometallics displaying a promising anticancer potential. The complexes [Fe2Cp2(CO)(µ-CO){µ-η1:η3-C(R3)C(R4)CN(R1)(R2)}]CF3SO3 (2a-c, 4a-d) were synthesized, assessed for their behavior in aqueous solutions (D2O solubility, Log Pow, stability in D2O/Me2SO-d6 mixture at 37°C over 48 h) and investigated for their antiproliferative activity against A2780 and A2780cisR ovarian cancer cell lines and the nontumoral one Balb/3T3 clone A31. Cytotoxicity data collected for 50 vinyliminium complexes were correlated with the structural properties (i.e. the different R1-R4 substituents) using the partial least squares methodology. A clear positive correlation emerged between the octanol-water partition coefficient and the relative antiproliferative activity on ovarian cancer cell lines, both of which appear as uncorrelated to the cancer cell selectivity. However, the different effects played by the R1-R4 substituents allow tracing guidelines for the development of novel, more effective compounds. Based on these results, three additional complexes (4p-r) were designed, synthesized and biologically investigated, revealing their ability to hamper thioredoxin reductase enzyme and to induce cancer cell production of reactive oxygen species.

N-Indolyl diiron vinyliminium complexes exhibit antiproliferative effects in cancer cells associated with disruption of mitochondrial homeostasis, ROS scavenging, and antioxidant activity.

The indole scaffold has been established as a key organic moiety for developing new drugs; on the other hand, a range of diiron bis-cyclopentadienyl complexes have recently emerged for their promising anticancer potential. Here, we report the synthesis of novel diiron complexes with an indole-functionalized vinyliminium ligand (2-5) and an indole-lacking analogue for comparative purposes (6), which were characterized by analytical and spectroscopic techniques. Complexes 2-6 are substantially stable in DMSO­d6 and DMEM-d solutions at 37 °C (8% average degradation after 48 h) and display a balanced hydrophilic/lipophilic behaviour (LogPow values in the range -0.32 to 0.47), associated with appreciable water solubility. The complexes display selective antiproliferative potency towards several cancer cells in monolayer cultures, mainly in the low micromolar range, with reduced toxicity towards noncancerous epithelial cells. Thus, the cytotoxicity of the complexes is comparable to or better than clinically used metallopharmaceutical cisplatin. Comparing the antiproliferative activity obtained for complexes containing different ligands, we confirmed the importance of the indolyl group in the mechanism of antiproliferative activity of these complexes. Cell-based mechanistic studies suggest that the investigated diiron vinyliminium complexes (DVCs) show cytostatic rather than cytotoxic effects and subsequently induce a population of cells to undergo apoptosis. Furthermore, the molecular mechanism of action involves interactions with mitochondrial DNA and proteins, the reactive oxygen species (ROS)-scavenging properties and antioxidant activity of these complexes in cancer cells. This study highlights the importance of DVCs to their cancer cell activity and reinforces their prospective therapeutic potential as anticancer agents.

η6-Coordinated ruthenabenzenes from three-component assembly on a diruthenium µ-allenyl scaffold.

The room temperature reactions with internal alkynes, RCCR, of the µ-allenyl acetonitrile complex [Ru2Cp2(CO)2(NCMe){µ-η1:η2-C1HC2C3Me2}]BF4 (1-NCMe), freshly prepared from the tricarbonyl precursor [Ru2Cp2(CO)3{µ-η1:η2-C1HC2C3Me2}]BF4, 1, proceeded with alkyne insertion into ruthenium-allenyl bond and allenyl-CO coupling, affording compounds [Ru2Cp2(CO)2{µ-η2:η5-C(R)C(R)C1HC2(C3MeCH2)C(OH)}]BF4 (R = Ph, 2; R = CO2Me, 3; R = CO2Et, 4) in 83-94% yields. Deprotonation of 2-4 by triethylamine gave [Ru2Cp2(CO)2{µ-η2:η5-C(R)C(R)CHC(CMeCH2)C(O)}] (R = Ph, 5; R = CO2Me, 6; R = CO2Et, 7) in 75-88% yields, and 2-4 could be recovered upon HBF4·Et2O addition to 5-7. All the products, 2-7, were fully characterized by elemental analysis, IR and multinuclear NMR spectroscopy. The structure of 2 was ascertained by single crystal X-ray diffraction and investigated by DFT calculations, revealing a six-membered ruthenacycle with Shannon aromaticity index in line with related compounds. The formation of ruthenium-coordinated ruthenabenzenes from a preexistent diruthenium scaffold is a versatile but underdeveloped approach exploiting cooperative effects typical of a dimetallic core.

Cyanide-alkene competition in a diiron complex and isolation of a multisite (cyano)alkylidene-alkene species.

The µ-(amino)alkylidyne complex [Fe2Cp2(CO)2(µ-CO){µ-CNMe(CH2CHCH2)}]CF3SO3, [1]CF3SO3, reacted with NBu4CN in dichloromethane affording the µ-(cyano)(amino)alkylidene [Fe2Cp2(CO)2(µ-CO){µ-C(CN)N(Me)(CH2CHCH2)}], 2, in 91% yield. Decarbonylation of 2 by using Me3NO in acetone at room temperature yielded [Fe2Cp2(CO)(µ-CO){µ-κ3C-C(CN)N(Me)(CH2CHCH2)}], 3, containing a multidentate alkylidene-alkene ligand occupying both a bridging site and a terminal site, in admixture with the µ-(amino)alkylidyne cyanide product [Fe2Cp2(CN)(CO)(µ-CO){µ-CN(Me)(CH2CHCH2)}], 4. The reaction of the µ-(amino)alkylidyne imine complex [Fe2Cp2(CO)(µ-CO)(NHCPh2){µ-CN(Me)(CH2CHCH2)}]CF3SO3, [7]CF3SO3, with NBu4CN gave 3 with an optimized yield of 75% via imine elimination. According to DFT calculations, 3 is less stable than its geometric isomer 4 by 13.4 kcal mol-1 and quantitative conversion to 4 was achieved by refluxing a THF solution of 3 for 2 hours. No replacement of alkene coordination occurred upon treating 3 with CO or PPh3. The previously unknown compounds 2, 3, 4 and [7]CF3SO3 were fully characterized by analytical and spectroscopic techniques and the structure of 3 was elucidated by single crystal X-ray diffraction.

Alkyne-alkenyl coupling at a diruthenium complex.

Dimetallic complexes are suitable platforms for the assembly of small molecular units, and the reactivity of bridging alkenyl ligands has been widely investigated to model C-C bond forming processes. Here, we report the unusual coupling of an alkenyl ligand, bridging coordinated on a diruthenium scaffold, with a series of alkynes, revealing two possible outcomes. The diruthenium complex [Ru2Cp2(Cl)(CO)(µ-CO){µ-η1:η2-C(Ph)CH(Ph)}], 2, was prepared in two steps from [Ru2Cp2(CO)2(µ-CO){µ-η1:η2-C(Ph)CH(Ph)}]BF4, [1]BF4, in 69% yield. Then, the reaction of 2 with C2(CO2Me)2, promoted by AgCF3SO3 in dichloromethane, afforded in 51% yield the complex [Ru2Cp2(CO)2{µ-η3:η2-C(Ph)CH(Ph)C(CO2Me)C(CO2Me)}]CF3SO3, [3]CF3SO3, containing a ruthenacyclopentene-based hydrocarbyl ligand. On the other hand, 2 reacted with other alkynes and AgX salts to give the butadienyl complexes [Ru2Cp2(CO)2{µ-η3:η2-C(R)CH(R')C(Ph)C(Ph)}]X (R = R' = H, [4]BF4; R = R' = Me, [5]CF3SO3; R = R' = Ph, [6]CF3SO3; R = Ph, R' = H, [7]CF3SO3), in 42-56% yields. All products were characterized by IR and NMR spectroscopy, and by single crystal X-ray diffraction in the cases of 2, [3]CF3SO3 and [6]BF4. DFT calculations highlighted the higher stability of [4-7]+-like structures with respect to the corresponding [3]+-like isomers. It is presumable that [3]+-like isomers initially form as kinetic intermediates, then undergo H-migration which is disfavoured in the presence of carboxylato substituents on the alkyne. Such hypothesis was supported by the computational optimization of the transition states for H-migration in the cases of R = R' = H and R = R' = CO2Me.

Screening the biological properties of transition metal carbamates reveals gold(I) and silver(I) complexes as potent cytotoxic and antimicrobial agents.

We report a screening study aimed to assess for the first time the air- and water-stability and the biological potential of simple metal-carbamates. These molecular metallic species are based on elements belonging to the groups 4-5, 7-9 and 11, and tin, and are easily available from inexpensive reagents. Complexes [Ag(O2CNEt2)] (13-Ag) and [Au(O2CNMe2)(PPh3)] (14-Au) resulted substantially stable in aqueous media and exhibited a potent in vitro cytotoxicity. Especially 13-Ag revealed a significant selectivity against the A549 lung adenocarcinoma and the A2780 ovarian cancer cell lines with respect to the noncancerous HEK293 cell line. Generation of ROS (reactive oxygen species) and mitochondrial membrane depolarization were recognized for 13-Ag and 14-Au; notwithstanding, the cell death mechanism is different in the two cases: apoptosis and cell cycle arrest in G0/G1 phase for 13-Ag; necroptosis and cell cycle arrest in S phase for 14-Au. Both 13-Ag and 14-Au are endowed with antibacterial activity, which is relatively stronger for 13-Ag towards Gram negative and for 14-Au towards Gram positive strains, respectively.

Non-precious metal carbamates as catalysts for the aziridine/CO2 coupling reaction under mild conditions.

The catalytic potential of a large series of easily available metal carbamates (based on thirteen different non-precious metal elements) was explored for the first time in the coupling reaction between 2-aryl-aziridines and carbon dioxide, working under solventless and ambient conditions and using tetraalkylammonium halides as co-catalysts. The straightforward synthesis of novel [NbCl3(O2CNEt2)2], NbCl, and [NbBr3(O2CNEt2)2], NbBr, is reported. The niobium complex NbCl, in combination with NBu4I, emerged as the best catalyst of the overall series to convert aziridines with small N-alkyl substituents into the corresponding 5-aryl-oxazolidin-2-ones.

Bypassing the Inertness of Aziridine/CO2 Systems to Access 5-Aryl-2-Oxazolidinones: Catalyst-Free Synthesis Under Ambient Conditions.

The development of sustainable synthetic routes to access valuable oxazolidinones via CO2 fixation is an active research area, and the aziridine/carbon dioxide coupling has aroused a considerable interest. This reaction features a high activation barrier and thus requires a catalytic system, and may present some other critical issues. Here, the straightforward gram-scale synthesis of a series of 5-aryl-2-oxazolidinones was developed at ambient temperature and atmospheric CO2 pressure, in the absence of any catalyst/co-catalyst. The key to this innovative procedure consists in the direct transfer of the pre-formed amine/CO2 adduct (carbamate) to common aziridine precursors (dimethylsulfonium salts), replacing the classical sequential addition of amine (intermediate isolation of aziridine) and then CO2 . The reaction mechanism was investigated by NMR spectroscopy and DFT calculations applied to model cases.

Iron(III) N,N-Dialkylcarbamate-Catalyzed Formation of Cyclic Carbonates from CO2 and Epoxides under Ambient Conditions by Dynamic CO2 Trapping as Carbamato Ligands.

Easily available and inexpensive FeIII carbamates were employed in the solvent-free synthesis of a series of cyclic carbonates from epoxides and CO2 at room temperature and atmospheric pressure, in the presence of a cocatalyst. Different experimental conditions (type and concentration of catalyst and cocatalyst, as well as reaction time) were investigated: Fe(O2 CNEt2 )3 and NBu4 Br acted as the best catalyst/cocatalyst combination, allowing the formation of propylene carbonate and 1,2-butylene carbonate with quantitative yield and selectivity in 24 h. According to NMR and DFT studies, the reaction proceeds with the dynamic trapping of carbon dioxide as a carbamato ligand.

Donation programme of returned medicines: role of donors and point of view of beneficiaries.

Background: Donation of returned medicines is a debated health policy issue as it is discouraged by WHO, but accepted in some countries. Methods: Lessons learned from a donation programme of returned medicines carried out in Europe were documented. Results: The donation programme we reviewed followed a strict protocol for collection, sorting and distribution of returned drugs, in order to avoid the major limitations associated with unused medicine donations. Over a period of 3 years, 23 145 boxes of medicines were donated to 14 organizations operating in Europe, Africa and Latin America. Conclusions: The donations covered about one-third of the volume of medicines used by beneficiary organizations. The programme helped to decrease expenditure by both patients and health facilities.

MoCl5 as an effective chlorinating agent towards α-amino acids: synthesis of α-ammonium-acylchloride salts and α-amino-acylchloride complexes.

The reactivity of MoCl5 with α-amino acids was investigated for the first time by choosing CH2Cl2 as the reaction medium. The interaction of MoCl5 with l-proline proceeded with Cl/O interchange and led to the formation of [NH2(CH2)3CHC(O)Cl][MoOCl4], 1, in 63% yield. The reactions of MoCl5 with l-phenylalanine, sarcosine, N,N-dimethylglycine and N,N-dimethyl-l-phenylalanine afforded the α-amino-acylchloride complexes MoOCl3[O[double bond, length as m-dash]C(Cl)CH(R)N(R')(R'')] (R = CH2Ph, R' = R'' = H, 2a; R = R' = H, R'' = Me, 2b; R = H, R' = R'' = Me, 2c R = CH2Ph, R' = R'' = Me, 2d), in ca. 70% yields. According to DFT studies, 2a,d are mononuclear Mo(v) octahedral complexes bearing a N,O-coordinated α-amino-acylchloride ligand. The presumed species formed during the first stages of the MoCl5/l-phenylalanine interaction were DFT-elucidated, thus the calculated Gibbs free energy profile for the multi-step reaction of MoCl5 with l-phenylalanine was traced. [NH3CH(CH2Ph)C(O)Cl][MoOCl4], 3, acting as an intermediate in the course of the formation of 2a, was isolated by combination of [NH3CH(CH2Ph)C(O)Cl][Cl] with MoOCl3.