Project Abstract

<p> This project work present the alkylating reaction of [Pt2(μ-S)2(PPh3)4] with boronic<br>acid alkylating agents.The reactivity of the metalloligand [Pt2(μ-S)2(PPh3)4] with the<br>boron-functionalized alkylating agents BrCH2(C6H4)B(OR)2 (R = H or C(CH3)2) was<br>investigated by electrospray ionization mass spectrometry (ESI-MS) in real time using<br>the pressurized sample infusion (PSI). The macroscopic reaction of [Pt2(μ-S)2(PPh3)4]<br>with one mole equivalent of alkylating agents BrCH2(C6H4)B{OC(CH3)2}2and<br>BrCH2(C6H4)B(OH)2 gave the dinuclear monocationic μ-sulfide thiolate complexes<br>[Pt2(μ-S){μ-SCH2(C6H4)B{OC(CH3)2}2}(PPh3)4]+ and [Pt2(μ-S){μ-S+CH2<br>(C6H4)B(OH)(O–)}(PPh3)4]. The products were isolated as the [PF6]– salts and<br>zwitterion respectively, and fully characterized by ESI-MS, IR, 1H and 31P NMR<br>spectroscopy and single crystal X-ray structure determinations. The alkylation<br>reaction of BrCH2(C6H4)B{OC(CH3)2}2 with [Pt2(μ-S)2(PPh3)4 + H]+was determined<br>via kinetic analysis by PSI-ESI-MS to be second order consistent with the expected<br>SN2 mechanism for an alkylation reaction. The PSI-ESI-MS microscale synthesis<br>showed that[Pt2(μ-S)2(PPh3)4]disappeared rapidly with consequent formation of<br>onlymonoalkylated cationic product, [Pt2(μ-S){μ-<br>SCH2(C6H4)B{OC(CH3)2}2}(PPh3)4]+. This was indicated by the immediate<br>appearance of the monoalkylated product peak at m/z 1720.6.The reaction came to<br>completion within 6 minutes after injection and no trace of any other product or<br>dialkylated species. The desk top synthesis observed after further stirring for six hours<br>also show the formation of no other product. The reaction ofBrCH2(C6H4)B(OH)2,<br>with({[Pt2(μ-S)2(PPh3)4] + H}+)within same time interval yielded three monocationic<br>species that were detected by ESI-MS and assignable to the three alkylated products<br>[Pt2(μ-S){μ-SCH2C6H5)(PPh3)4]+, m/z 1593.4 from the loss of B(OH)2 moiety; a<br>hemiketal-like species [Pt2(μ-S){μ-SCH2(C6H4)B(OH)(OCH3)}(PPh3)4]+, m/z 1651.5<br>and [Pt2(μ-S){μ-SCH2(C6H4)OH}(PPh3)4]+, m/z 1609.5. The laboratory scale<br>synthesis indicated the same products.The masses were identified by comparing the<br>experimental isotope patterns with calculated ones. No peak was observed in the<br>mass spectrum that was attributable to the formation of the expected product [Pt2(μ-<br>S){μ-SCH2(C6H4)B(OH)2}(PPh3)4]+. The structural determination by X-ray<br>diffraction showed that the compound formed was a zwitter ion (neutral complex)<br>[Pt2(μ-S){μ-S+CH2(C6H4)B(OH)(O-)}(PPh3)4]. [Pt2(μ-S){μ-S+CH2(C6H4)B(OH)(O-<br>)}(PPh3)4] is a neutral species and not detectable in ESI-MS. 1H NMR spectra showed<br>a complicated set of resonances in the aromatic region due to the terminal<br>triphenylphosphine ligands and were broadly assigned as such. However, SCH2<br>hydrogen atoms were easily identified as broad peaks at δ 3.59 ppm and 3.60 ppm for<br>[Pt2(μ-S){μ-SCH2(C6H4)B{OC(CH3)2}2}(PPh3)4]+PF6 and [Pt2(μ-S){μ-<br>S+CH2(C6H4)B(OH)(O-)}(PPh3)4], respectively. The monoalkylated products shows<br>IR and 31P{1H} NMR spectra expected of the complexes. The OH vibration (3336 cm-<br>1) in 2.1 shifted to 3435 cm-1 in 2.1a. The absorption bands of the B-O bond in 2.2<br>(1355 cm-1) and 2.1 (1350 cm-1) shifted to 1360 cm-1 and 1367 cm-1 in 2.2a·(PF6) and<br>2.1a respectively. The 31P{1H} NMR spectra showed nearly superimposed central<br>resonances and clearly separated satellite peaks due to 195Pt coupling. The 1J(PtP)<br>coupling constants showed the differences due to the trans influences of the<br>substituted and the unsubstituted sulfide centers. The trans influence of the<br>unsubstituted sulfide is greater than the thiolate (substituted) species demonstrated by<br>the coupling constants at (2628 and 3291 Hz) for 2.2a·(PF6) and (2632 and 3272 Hz)<br>2.1a,respectively. <br></p>

Project Overview

<p> 1.0 Introduction<br>1.1 Background of Study<br>The diverse study on platinum and sulfur element has been possible due to their rich<br>individual chemistries.Their compounds have been extensively studied due to their<br>wide range of applications in both biology and industry1. Platinum was first<br>discovered in 1735 by Don Antonio de Ulloa. It has high melting point and good<br>resistance to corrosion and chemical attack2. Consequence to its resistance to wear<br>and tarnish and its beautiful looks, it is employed in jewellery production3,4. It is also<br>used in laboratory equipment, electrical contacts, catalytic converters, dentistry<br>equipment, electrodes, antioxidation processes, catalysis, biomedical applications and<br>hard disk4,5,6,7, 8-11. Platinum compounds like cisplatin, carboplatin and oxaliplatin are<br>used in cancer treatments12,13,14. The use of cisplatin in cancer chemotherapy is<br>limited by ototoxicity, emetogenesis effect, neurotoxicity, and nephrotoxicity of the<br>drug15-18. It has been suggested that the toxicity of the drug is as a result of bonding<br>between platinum and protein sulfur atoms19.<br>Platinum exists in different oxidation states, 0 to +6, due to its vacant d<br>orbitals. The most common oxidation state is +2 including non-even20 with +1 and +3<br>found in dinuclear Pt-Pt bonded complexes. These properties make platinum form<br>coordination compounds easily.<br>Sulfur is commonly used in the manufacturing of important chemical like<br>sulfuric acid. It is also used to refine oil and in processing ores11. It is an essential<br>element in most biochemical processes. Sulfur compounds serve as substrates in<br>biochemical process (serving as an electron acceptor in anaerobic respiration of<br>2<br>sulfate-sulfur eubacteria), fuels (electron donors) and respiratory (oxygen alternative)<br>in metabolism22. Vitamins such as thiamine and biotin, antioxidants like thioredoxin<br>and glutathiones, and myriads of enzymes contain organic sulfur23. Organic sulfur has<br>an anti-neoplastic effect and used in oral and other cancers treatment24.<br>Sulfur ligands coordinate with most transition metals in different oxidation<br>states25. The chemical properties of sulfur as a versatile coordination ligand is<br>illustrated by its tendency to extend its coordination from terminal groups example<br>([Mo2S10]2-)26 to μ-sulfido group e.g. [Pt2(μ-S)2(PPh2Py)4]27 and to an encapsulated<br>form e.g. [Rh17(S)2(CO)32]3- consisting of a S-Rh-S moiety in the cavity of a<br>rhodium-carbonyl cluster28. It has the propensity to catenate and give rise to<br>polysulfide ligands (Sn<br>2-) with n ranging from 1 to 8. Sulfur ligands coordination<br>chemistry is widely manifested in the variety of structures it forms with most of the<br>transition metals25. The important roles of metal sulfide compounds are seen in<br>catalysis29, bioinorganic and rich solid-state chemistry 30. The metal-sulfur bonding<br>serves as key part of the active site component in reactivity of the biological<br>macromolecule31-35.<br>{Pt2S2} chemistry is dated back to 1903 when Hofmann and Hochlen reported<br>a work on isolation of the first platinum-sulfur complex [(NH4)2[Pt(η2-S5)3]36.<br>Platinum sulfido complexes are classified as homometallic sulfido complexes and<br>heterometallic sulfido complexes. The homometallic sulfido complex of platinum was<br>further classified into groups consisting of the platinum atom metal-metal bond<br>bridged by single sulfur, and that in which the two non-bonded platinum atoms are<br>held together by two sulfur ligands. The sulfur atoms, in both complexes have the<br>capability of bonding further to other metals or ligands. Following the development<br>reported by Hofmann and Hochlen in 1903, a metal-metal bond bridged by single<br>3<br>sulfur complex [Pt2(μ-S)(CO)2(PPh3)3] was reported by Baird and Wilkinson as a<br>product of the reaction of [Pt(PPh3)3] with COS37. On heating in chloroform, the<br>intermediate [Pt(PPh3)2(COS)] gave an orange air-stable compound which was<br>identified using infra-red spectroscopy and elemental analysis technique38. X-ray<br>crystallography showed that the compound had only one CO ligand and the structure<br>was reported by Skapski and Troughton39.<br>S<br>Pt Pt<br>Ph3P<br>Ph3P<br>PPh3<br>CO<br>Figure 1.1: Structure of[Pt(PPh3)2(COS)] formed by the reaction of [Pt(PPh3)3] with<br>COS.<br>A related synthesis which uses CS2 instead of COS was also reported40. The reaction<br>of [Pt(dppe)(CS2)] with [Pt(PPh3)2(C2H 4)] is a typical example of the synthetic<br>reaction and gives the complex in Figure 1.2.<br>S<br>Pt Pt<br>PPh2<br>PPh2<br>PPh3<br>CS<br>Figure 1.2: Product for the reaction of [Pt(dppe)(CS2)] with [Pt(PPh3)2(C2H4)]<br>Chatt and Mingos41 in 1970 reported a related complex [Pt2(PMe2Ph)(μ-S)2]4<br>– having<br>two non-bonded platinum atoms held together by two sulfur ligands so-called {Pt2(μ-<br>S)2}. Ugo et al26 followed almost immediately in a study of the reaction of zerovalent<br>platinum phosphine complexes with H2S and or elemental sulfur to give di-μ-<br>4<br>sulfidotetrakis-(triphenylphosphine) diplatinum(II) [Pt2(μ-S)2(PPh3)4] 1.0. Similar<br>complexes having different terminal ligands that have been reported also include: 2-<br>(diphenylphosphino)pyridine [Pt2(μ-S)2(PPh2Py)4]27 1.2, Redox active 1,1’-<br>bis(diphenyiphosphino) ferrocene [Pt2(μ-S)2(dppf)2]36 1.3, 1,2-bis<br>(diphenylphosphino)[Pt2(μ-S)2(dppe)2]42 1.4, dimethylphenylphosphane<br>[Pt2(PMe2Ph)4(μ-S)2]43 1.5 , 1,3-bis(diphenylphosphino) propane [Pt2(μ-S)2(dppp)2]<br>1.644, [Pt2(μ-S)2(Ptolyl3)2]45 1.7, diphosphines such as (Ph2P(CH2S)nPPh2)2<br>46 (n = 2,3).<br>Chiral phosphine such as O-Isopropylidene-2,3-dihydroxy-1,4-<br>bis(diphenylphosphino)butane (DIOP)47 have also been studied but to a lesser extent.<br>[Pt2(μ-S)2(PPh3)4] is the most widely studied of the complexes due to its ease of<br>preparation, from air-stable starting materials, and its tendency to produce crystalline<br>derivatives which was highlighted in an excellent review by Fong and Hor48.<br>González-Duarte46 and co-workers also worked on the development of other sulfidebridged<br>complexes with the {Pt2(μ-S)2} core, as well as the synthesis of its<br>derivatives, structure, and reactivities. They also synthesized series of di-μ-thiolate<br>complexes with the {M2(μ-S)2} core (where M = Ni, Pd or Pt),49,50,51 provided the<br>molecular orbital study of the hinge distortion of the {Pt2(μ-S)2} ring52 and used<br>chelating diphosphines as terminal ligands53.<br>1.2 Statement of Problem<br>Sulfide alkylation chemistry of di-μ-sulfidotetrakis-(triphenylphosphine)<br>diplatinum(II) [Pt2(μ-S)2(PPh3)4] (1.0) using alkyl, aryl, and functionalised organic<br>electrophiles46,54 to form thiolate55 ligands has been a subject of researchers interest.<br>However, no derivatives of [Pt2(μ-S)2(PPh3)4] containing boronic acid electrophiles,<br>4-bromomethyl phenyl boronic acid pinacolester, BrCH2(C6H4)B{OC(CH3)2}2 and 4-<br>bromomethylphenylboronic acid, BrCH2(C6H4)B(OH)2 or any metalloid<br>5<br>functionalized thiolate ligands has been synthesised using sulfide alkylation. Kinetic<br>analysis has not been previously applied in the investigation of the synthetic<br>complexities surrounding the alkylation of {Pt2S2}. Boronic acid derivatives have<br>been used in the synthesis of bi- and polyaryl compounds via the Suzuki–Miyaura<br>coupling reactions56-60. To date, no derivatives of 1.0 containing boron or any<br>metalloid functionalized thiolate ligands have been synthesized using sulfide<br>alkylation. We present in this report the first experimental kinetic analysis of<br>alkylation of 1.0, and the first synthesis and characterization of boronic acid<br>derivatives of 1.0. The isolation and crystallographic identification of the dinuclear<br>structures incorporating boron thiolate substituents suggests that useful synthetic<br>precursor groups can be incorporated into 1.0, and in particular open up avenues for<br>preparing larger multinuclear assemblies on the nanometer scale. Therefore there is a<br>need to further develop the alkylation chemistry of this system by investigation the<br>reactivity of other potentially synthetic precursor groups. Detailed investigation of the<br>reaction kinetics by careful monitoring of the reaction in real time using Pressurized<br>Sample Infusion Electrospray Ionization Mass Spectrometry (PSI-ESI-MS) has never<br>been reported.<br>1.3 Justification of Study<br>Despite the fact that much work has been reported on 1.0 complex, no derivatives of<br>1.0 containing boron has been used to generate coordinated functionalized thiolate<br>ligands (-SR) on 1.0. In view of this, this research work will investigate the<br>incorporation of new functionalized organic electrophiles of boronic acid derivatives<br>and monitor the reaction kinetics with the aid of Pressurized Sample Infusion<br>Electrospray Ionization Mass Spectrometry (PSI-ESI-MS). This work will present the<br>first study on the monoalkylation chemistry of 1.0 towards organic electrophiles<br>6<br>BrCH2(C6H4)B{OC(CH3)2}2 and BrCH2(C6H4)B(OH)2.The chemistry of this system<br>is of great interest due to the reactivity of 1.0 with different electrophiles as observed<br>in the ESI-MS, NMR and IR spectroscopic result.<br>1.4 Aims and Objectives of the Study<br>The objectives of this study are:<br>1. To design, synthesize and characterise functionalized monoalkylated<br>derivatives of 1.0; acquire and analyze the kinetic data of the monoalkylation<br>reaction between boronic acid derivatives BrCH2(C6H4)B{OC(CH3)2}2 and<br>BrCH2(C6H4)B(OH)2.<br>2. Use the data obtained from (1) to incorporate the boronic acid derivatives in<br>the desktop/laboratory scale synthesis.<br>3. Characterize the isolated products using conventional spectroscopic technique:<br>NMR, IR, and X-ray crystallography. <br></p>