Central Platinum Atom Research Articles

A([18]crown‐6)]2[Pt(CO)3] ⋅ 10 NH3(A=K, Rb) – A crystal structure containing the long postulated [Pt(CO)3]2−

AbstractThe compound [A([18]crown‐6]2[Pt(CO)3] ⋅ 10 NH3(A=K, Rb, [18]crown‐ 6=1,4,7,10,13,16‐Hexaoxacyclooctadecane) containing the anion [Pt(CO)3]2−was the unexpected result of a reaction between K6Rb6Ge17, Pt(CO)2(PPh3)2, [18]crown‐6 and [2.2.2]‐crypt. This compound represents the first example of a mononuclear carbonyl platinate and expands the list of known group 10 carbonyl metallates. The central anion has a trigonal planar shape with an approximate D3hsymmetry. Theoretical investigations confirm the trigonal planar structure of the carbonylate and give insight into the electronic structure. The calculations reveal a strong charge density at the central platinum atom, while the HOMO shows a dispersion of the residual electrons under and over the carbonyl plane.

Mixed Valence Pt(II),Pt(IV),Pt(II) Complexes from a Diplatinum(III) Synthon and Sulfur-Based Anions

The coordination of the S-based anions, thiophenoxide (PhS–, a), ethyl xanthogenate (EtOCS2–, b), 2-mercaptopyridinate (pyS–, c), and 2-mercaptopyrimidinate (pymS–, d), to the central platinum atom...

Triplet state structure-property relationships in a series of platinum acetylides: effect of chromophore length and end cap electronic properties.

To develop quantitative structure-spectroscopic property relationships in platinum acetylides, we investigated the triplet state behavior of nominally centrosymmetric chromophores trans-Pt(PBu3)2(C[triple bond, length as m-dash]C-Phenyl-X)2, where X = diphenylamino, NH2, OCH3, t-Bu, CH3, H, F, benzothiazole, CF3, CN, and NO2. We measured ground state absorption, phosphorescence, excitation and triplet state absorption spectra and triplet lifetimes. By DFT we calculated the phosphorescence emission energy (ET), the spin density on the end cap (SD(X)), triplet state geometry and the distance between the triplet centroid and the central platinum atom (RS-Pt(X)). Compounds with electron-donating X have smaller triplet state lifetime, blue-shifted phosphorescence and larger triplet potential energy surface displacement associated with the C[triple bond, length as m-dash]C bond. Compounds with electron-withdrawing X have larger triplet lifetime, red-shifted phosphorescence and smaller triplet potential energy surface displacement associated with the C[triple bond, length as m-dash]C bond. The range of spin-orbit-coupling between the platinum atom and the triplet centroid was determined to be 6 Å. The quantity RS-Pt is shown to be a linear function of one-dimensional well length calculated from experimental ET. The multiple examples demonstrate RS-Pt is a useful descriptor for analyzing triplet state behavior.

Reversibly core-crosslinked PEG-P(HPMA) micelles: Platinum coordination chemistry for competitive-ligand-regulated drug delivery

HypothesisThe presence of pendant thioether groups on poly(ethylene glycol)-poly(N(2-hydroxypropyl) methacrylamide) (PEG-P(HPMA)) block copolymers allows for platinum-mediated coordinative micellar core-crosslinking, resulting in enhanced micellar stability and stimulus-responsive drug delivery. ExperimentsA new PEG-P(HPMA) based block copolymer with pendant 4-(methylthio)benzoyl (MTB) groups along the P(HPMA) block was synthesized by free radical polymerization of a novel HPMA-MTB monomer using a PEG based macro-initiator. As crosslinker the metal-organic linker [ethylenediamineplatinum(II)]2+ was used, herein called Lx, which is a coordinative linker molecule that has been used for the conjugation of drug molecules to a number of synthetic or natural carrier systems such as hyperbranched polymers and antibodies. FindingsThe introduction of Lx in the micellar core results in a smaller size, a lower critical micelle concentration and a better retention of the hydrophobic drug curcumin thanks to coordination bonds between the central platinum atom of Lx and thioether groups on different polymer chains. The drug release from Lx crosslinked micelles is significantly accelerated under conditions mimicking the intracellular environment due to competitive coordination and subsequent micellar de-crosslinking. Because of their straightforward preparation and favorable drug release characteristics, core-crosslinked Lx PEG-P(HPMA) micelles hold promise as a versatile nanomedicine platform.

Crystallographic and structural characterization of heterometallic platinum clusters Part VIII. Heteronona- and heterodecanuclear clusters

Abstract This review classifies and analyses fifty heteronona- and heterodecanuclear Pt clusters of metal composition: Pt4Ru5, Pt3Ru6, Pt20sr PtRh8, PtAu8; Pt6M4, Pt5M5, Pt4M6, Pt3M2, Pt2M8, PtM9, Pt3Ru6M and PtAu8M. There are nine different heterometals: M = Ru, Au, Ag, Cu, Hg, Os, Rh, Ir and Fe, of which Ru and Au are the most frequent. The clusters crystallize mostly into two crystal classes, monoclinic (74%) and triclinic (18%), and their structures are complex. Three triangular layers of nine metal atoms arranged in the form of a face-shared bioctahedron are common in the series of heterononanuclear clusters. In the series of heterodecanuclear clusters distorted skeletal icosahedrons, where a central platinum atom is surrounded by nine metal atoms, and face (edge) shared (fused) bioctahedral cluster of the metal atoms are the most common. The most frequent ligands are CO and PPh3. The shortest metal-metal bond distances are: 2.540(4) Å (Pt-Fe), 2.580(2) Å (Ru-Ru), 2.584 Å (Pt-Pt) and 2.629(4) Å (Cu-Au). Several relationships between the structural parameters were found and are discussed. Some clusters contain two crystallographically independent molecules within the same crystal and are examples of distortion isomerism.

Synthesis, crystal structure and antimicrobial studies of chlorido(dimethylsulfoxide-κS)(pyrrolidinedithiocarbamato-κ2S,S/)platinum(II)

Abstract Platinum(II) complexes, [Pt(PDTC)(H2O)Cl] and [Pt(PDTC)(DMSO)Cl] (1) (PDTC = pyrrolidinedithiocarbamate) have been prepared and characterized by IR, NMR and X-ray crystallographic methods. In the crystal structure of 1 the central platinum atom is coordinated to two sulfur atoms of PDTC, one sulfur atom of DMSO and one chloride ion adopting a square planar geometry with the average cis and trans bond angles of 90.00° and 171.62° respectively. The 1H and 13C NMR spectral data indicate the coordination of both PDTC and DMSO to platinum(II). The title complex was screened for antimicrobial effects and the results show that it exhibits significant activity against gram-negative bacteria (E. coli, P. aeruginosa), while the activities are moderate against molds (A. niger, P. citrinum) and yeasts (C. albicans, S. serevisaiae).

Photophysical Properties of a Series of Electron-Donating and -Withdrawing Platinum Acetylide Two-Photon Chromophores

To explore spectroscopic structure-property relationships in platinum acetylides, we synthesized a series of complexes having the molecular formula trans-bis(tributylphosphine)-bis(4-((9,9-diethyl-7-ethynyl-9H-fluoren-2-yl)ethynyl)-R)-platinum. The substituent, R = NH(2), OCH(3), N(phenyl)(2), t-butyl, CH(3), H, F, benzothiazole, CF(3), CN, and NO(2), was chosen for a systematic variation in electron-donating and -withdrawing properties as described by the Hammett parameter σ(p). UV/vis, fluorescence, and phosphorescence spectra, transient absorption spectra on the fs-ps time scale, and longer time scale flash photolysis on the ns time scale were collected. DFT and TDDFT calculations of the T(1) and S(1) energies were performed. The E(S) and E(T) values measured from linear spectra correlate well with the calculated results, giving evidence for the delocalized MLCT character of the S(1) state and confinement of the T(1) exciton on one ligand. The calculated T(1) state dipole moment ranges from 0.5 to 14 D, showing the polar, charge-transfer character of the T(1) state. The ultrafast absorption spectra have broad absorption bands from 575 to 675 nm and long wavelength contribution, which is shown from flash photolysis measurements to be from the T(1) state. The T(1) energy obtained from phosphorescence, the T(1)-T(n) transition energy obtained from flash photolysis measurements, and the triplet-state radiative rate constant are functions of the calculated spin density distribution on the ligand. The calculations show that the triplet exciton of chromophores with electron-withdrawing substituents is localized away from the central platinum atom, red-shifting the spectra and increasing the triplet-state lifetime. Electron-donating substituents have the opposite effect on the location of the triplet exciton, the spectra, and the triplet-state lifetime. The relation between the intersystem crossing rate constant and the S(1)-T(1) energy gap shows a Marcus relationship with a reorganization energy of 0.83 eV. The calculations show that intersystem crossing occurs by conversion from a nonpolar, delocalized S(1) state to a polar, charge-transfer T(1) state confined to one ligand, accompanied by conformation changes and charge transfer, supporting the experimental evidence for Marcus behavior.

Tellurium(0) as a Ligand: Synthesis and Characterization of 2-Pyridyltellurolates of Platinum(II) and Structures of [Pt{2-Te-3-(R)C5H3N}2Te(PR′3)] (R = H or Me)

Treatment of toluene solutions of the ditellurides [Te(2){C(5)H(3)N(R)-3}(2)] (R = H or Me) with [Pt(PPh(3))(4)] yielded two types of complexes, [Pt{2-Te-3-(R)C(5)H(3)N}(2)(PPh(3))(2)] (1a-d) as the major products and [Pt{2-Te-3-(R)C(5)H(3)N}(2)Te(PPh(3))] (2a-d) as minor products. The above complexes can also be obtained by the reaction of [PtCl(2)(PR'(3))(2)] (PR'(3) = PPh(3) or PPh(2)(2-C(5)H(4)N)) with 2 equiv of Na(2-Te-C(5)H(3)R). The complexes were characterized by elemental analyses and UV-vis, NMR ((1)H and (31)P), and (in part) XPS spectroscopy. The molecular structures of [Pt(2-Te-C(5)H(4)N)(2)Te(PPh(3))] (2a) and [Pt{2-Te-C(5)H(3)(Me)N}(2)Te(PPh(3))] (2b) were established by single crystal X-ray diffraction. Both complexes exhibit a distorted square-planar configuration at the platinum(II) centers. The two mutually trans positioned 2-pyridinetellurolate ligands [2-Te-C(5)H(3)(R)N] coordinate to the central platinum atom in a monodentate fashion through the tellurium atoms. The tellurium(0) atom adopts a "bent T" configuration as it is bridging the 2-Te- C(5)H(3)(R)N molecules via N-Te-N bonds (166 degrees angle) and coordinates to Pt(II) in the trans position to PPh(3). The novel bis(pyridine)tellurium(0) arrangement resembles the bis(pyridine)iodonium structure. The calculated NICS indices and ELF functions clearly show that the compounds 2a and 2b are aromatic in the region defined by the Te-C-N-Te-Pt five-membered rings.

The Extension of the Solid‐Angle Concept to Bidentate Ligands

AbstractIn search of an applicable parameter to express the steric requirement of bidentate ligands, the generalised equivalent cone angle Θ–b is established. It is designed in the style of the solid‐angle concept for monodentate ligands, utilising crystal structure data. Its reliability is tested with bidentate phosphanes coordinated to a central platinum atom. Therefore, a detailed evaluation of the Cambridge Database for platinum complexes with bridging phosphanes is performed. Herein, we present the results of the analysis of more than 900 molecular structures and over 280 different bidentate phosphanes. We intend to establish diselenolatoplatinum(II) complexes as model compounds for the fast prediction of Θ–b instead of calculating a multiplicity of molecular structures that is often not available. The complexes reported in Part 1 of this publication turn out to be rather acceptable for rough estimates of the generalised equivalent cone angle. On the other hand, the compounds are used to demonstrate the practicability of the concept, which is easily extended to other bidentate ligands, as is shown for the 2,2‐bis(hydroxymethyl)‐1,3‐diselenolato moiety. In conclusion, the generalised equivalent cone angle Θ–b proves to be a feasible parameter for the steric demand of bidentate ligands.

Platinum Acetylide Two-Photon Chromophores

To explore the photophysics of platinum acetylide chromophores with strong two-photon absorption cross-sections, we have investigated the synthesis and spectroscopic characterization of a series of platinum acetylide complexes that feature highly pi-conjugated ligands substituted with pi-donor or -acceptor moieties. The molecules (numbered 1-4) considered in the present work are analogs of bis(phenylethynyl)bis(tributylphosphine)platinum(II) complexes. Molecule 1 carries two alkynyl-benzothiazolylfluorene ligands, and molecule 2 has two alkynyl-diphenylaminofluorene ligands bound to the central platinum atom. Compounds 3 and 4 possess two dihexylaminophenyl substituents at their ends and differ by the number of platinum atoms in the oligomer "core" (one vs two in 3 and 4, respectively). The ligands have strong effective two-photon absorption cross-sections, while the heavy metal platinum centers give rise to efficient intersystem crossing to long-lived triplet states. Ultrafast transient absorption and emission spectra demonstrate that one-photon excitation of the chromophores produces an S1 state delocalized across the two conjugated ligands, with weak (excitonic) coupling through the platinum centers. Intersystem crossing occurs rapidly (Kisc approximately 1011 s-1) to produce the T1 state, which is possibly localized on a single conjugated fluorenyl ligand. The triplet state is strongly absorbing (epsilonTT > 5 x 104 M-1 cm-1), and it is very long-lived (tau > 100 micro s). Femtosecond pulses were used to characterize the two-photon absorption properties of the complexes, and all of the chromophores are relatively efficient two-photon absorbers in the visible and near-infrared region of the spectrum (600-800 nm). The complexes exhibit maximum two-photon absorption at a shorter wavelength than 2lambda for the one-photon band, consistent with the dominant two-photon transition arising from a two-photon-allowed gerade-gerade transition. Nanosecond transient absorption experiments carried out on several of the complexes with excitation at 803 nm confirm that the long-lived triplet state can be produced efficiently via a sequence involving two-photon excitation to produce S1, followed by intersystem crossing to produce T1.

Asymmetry in Platinum Acetylide Complexes: Confinement of the Triplet Exciton to the Lowest Energy Ligand

To determine structure-optical property relationships in asymmetric platinum acetylide complexes, we synthesized the compounds trans-Pt(PBu3)2(C[triple bond]CC6H5)(C[triple bond]C-C6H4-C[triple bond]CC6H5) (PE1-2), trans-Pt(PBu3)2(C[triple bond]CC6H5)(C[triple bond]C-C6H4-C[triple bond]C-C6H4-C[triple bond]CC6H5) (PE1-3) and trans-Pt(PBu3)2(C[triple bond]C-C6H4-C[triple bond]CC6H5)(C[triple bond]C-C6H4-C[triple bond]C-C6H4-C[triple bond]CC6H5) (PE2-3) that have different ligands on either side of the platinum and compared their spectroscopic properties to the symmetrical compounds PE1, PE2 and PE3. We measured ground state absorption, fluorescence, phosphorescence and triplet state absorption spectra and performed density functional theory (DFT) calculations of frontier orbitals, lowest lying singlet states, triplet state geometries and energies. The absorption and emission spectra give evidence the singlet exciton is delocalized across the central platinum atom. The phosphorescence from the asymmetric complexes comes from the largest ligand. Time-dependent (TD) DFT calculations show the S1 state has mostly highest occupied molecular orbital (HOMO) --> lowest unoccupied molecular orbital (LUMO) character, with the LUMO delocalized over the chromophore. In the asymmetric chromophores, the LUMO resides on the larger ligand, suggesting the S1 state has interligand charge transfer character. The triplet state geometries obtained from the DFT calculations show distortion on the lowest energy ligand, whereas the other ligand has the ground state geometry. The calculated trend in the triplet state energies agrees very well with the experimental trend. Calculations of triplet state spin density also show the triplet exciton is confined to one ligand. In the asymmetric complexes the spin density is confined to the largest ligand. The results show Kasha's rule applies to these complexes, where the triplet exciton moves to the lowest energy ligand.

Spectroscopic Characterization of a Series of Platinum Acetylide Complexes Having a Localized Triplet Exciton

In this work, we describe the spectroscopic properties of a series of platinum complexes containing one acetylide ligand per platinum, having the chemical formula trans-Pt(PBu(3))(2)((C[triple bond]CC(6)H(4))(n)()-H)Cl, n = 1-3 (designated as half-PEn-Pt) and compare their spectroscopic behavior with the well-characterized series trans-Pt(PBu(3))(2)((C[triple bond]CC(6)H(4))(n)-H)(2), n = 1-3 (designated as PEn-Pt). This comparison aims to determine if the triplet state of PEn-Pt is confined to one ligand or delocalized across the central platinum atom. We measured ground-state absorption spectra, fluorescence spectra, phosphorescence spectra, and triplet-state absorption spectra. The ground-state absorption spectra and fluorescence spectra both showed a blue shift when comparing half-PEn-Pt with PEn-Pt, showing the S(1) state is delocalized across the platinum. In contrast, the phosphorescence spectra of the two types of compounds had the same 0-0 band energy, showing the T(1) state was confined to one ligand in PEn-Pt. The triplet state absorption spectra blue shifted when comparing half-PEn-Pt with PEn-Pt, showing the T(n) state was delocalized across the central platinum. This comparison supports recently published work that suggested this confinement effect (Rogers, J. E et al. J. Chem. Phys. 2005, 122, 214701).

Synthesis and characterization of trimethylplatinum(IV) complexes with (2-dimethylaminoethyl)organochalcogenides (Me 2NCH 2CH 2ER; E = S, Se, Te). X-ray crystal structure of [PtMe 3Br(Me 2NCH 2CH 2SC 6H 4Me-4)

Trimethylplatinum(IV) complexes of the type [PtMe 3X(Me 2NCH 2CH 2ER)] (X = Cl, Br, I; ER = SBu t, SC 6H 4Me-4, SPh, SePh, TePh) have been prepared and characterized by elemental analysis and NMR ( 1H and 13C) spectral data. The structure of [PtMe 3Br(Me 2NCH 2CH 2SC 6H 4Me-4)] has been determined by single-crystal X-ray diffraction. The central platinum atom is coordinated by three fac-methyl groups and nitrogen, sulphur and bromine atoms. The five-membered chelate ring PtNCCS is non-planar.

Tri- and tetra-nuclear homo- or hetero-metallic palladium(II) and platinum(II) complexes with double halide bridges. Molecular structure of [NBu4]2[(C6F5)2Pt(µ-Cl)2Pt(µ-Cl)2Pt(C6F5)2

By treating cis-[M(C6X5)2(thf)2](M = Pd or Pt, X = F or Cl, thf = tetrahydrofuran) with [M′X′4]2– or [M′2(µ-X′)2X′4]2–(M′= Pd or Pt; X′= Cl or Br) in a 2:1 ratio tri- or tetra-nuclear, homo- or heterometallic complexes of the types [NBu4]2[(C6X5)2M(µ-X′)2M′(µ-X′)2M(C6X5)2] or [NBu4]2[(C6X5)2M(µ-X′)2M′(µ-X′)2M′(µ-X′)2M(C6X5)2] can be obtained. The molecular structure of the trinuclear anion with M = M′= Pt, X = F, X′= Cl has been established by single-crystal X-ray crystallography. The anion is centrosymmetric, showing a square-planar PtCl4 central unit embraced by two Pt(C6F5)2 terminal moieties bonded to the central platinum atom through double chloride bridges.

Synthesis and reactivity of trinuclear complexes of platinum containing the single bridging ligand SC4H8. Molecular structure of [NBu4]2[trans-PtCl2{(µ-SC4H8)Pt(C6F5)3}2

Trinuclear complexes of the type [NBu4]2[trans-PtX2{(µ-SC4H8)Pt(C6F5)3}2](X = Cl,Br,I, or C6F5;SC4H8= tetrahydrothiphene)(1)–(4) have been prepared form trans-[PtX2(SC4H8)2] and NBu4[Pt(C6H5)3(OCMe2)](molar ratio 1:2). The SC4H8 ligands act as the single bridge between the central platinum atom and the two terminal ones. Attemps to prepare similar trinuclear complexes with singly bridging halide ligands failed since the reaction between trans-[PtCl2(py)2](py = pyridine) and NBu4[Pt(C6F5)3(OCMe2)](molar ratio 1:2) does not take place, while trans-[Ptl2(py)2] or [PtBr2(cod)](cod = cyclo-octa-1,5-diene), under similar conditions, yield cis-[Pt(C6F5)2(py)2] and [NBu4]2[Pt2(µ-I)2(C6F5)4] or [Pt(C6F5)2(cod)] and [NBu4]2[Pt2(µ-Br)2(C6F5)4] respectively. The trinuclear derivatives (1) and (3) react with neutral ligands L to give different mononuclear complexes, depending on the ligand L: when L = PPh3, NBu4[Pt(C6F5)3(SC4H8)] and cis-[PtX2(PPh3)2]; when L = CO, NBu4[Pt(C6F5)3(CO)] and trans-[PtCl2(SC4H8)2]. The molecular structure of [NBu4]2[trans-PtCl2{(µ-SC4H8)Pt(C6F5)3}2] has been established by a single-crystal X-ray diffraction study. The compound forms triclinic cryctals in the space group P, with Z= 1 and unit-cell dimensions a= 12.463(3), b= 12.487(3), c= 15.137(3)A, α= 85.68(15), β= 66.04(2), and γ= 87.04(1)°. The structure was refined to R= 0.048 and R′= 0.048. The central platinum atom in the trinuclear anion [trans-PtCl2{(µ-SC4H8)Pt(C6F5)3}2]2– lies on a crystallographic centre of symmetry and is bonded to two Cl atoms and two S atoms (from two SC4H8 ligands), the latter acting as bridging ligands between the central and the terminal Pt atoms.

Cisplatin ( cis-diamminedichloroplatinum II)

<h2>Summary</h2><h3>Preclinical</h3> <ul><li>1.Cisplatin is a co-ordination complex of a central platinum atom, two chlordies and two ammonia molecules in the "cis" position.</li><li>2.A prime mechanism of inhibition of tumor growth by cisplatin appears to be inhibition of DNA synthesis.</li><li>3.Cisplatin produces intrastrand and interstrand crosslinks in DNA.</li><li>4.The plasma t_1/2α of cisplatin (as determined by platinum measurements) was 30–60 min. The t_1/2β was 2–3 days.</li><li>5.Urinary excretion accounted for 60–70% and 27–45% of the administered dose of cisplatin in animals and humans respectively.</li><li>6.Cisplatin was rapidly bound to plasma proteins after i.v. administration with a plasma t_1/2β of the "free durg" of 32–53 min.</li><li>7.The principal dose limiting toxicity of cisplatin in animals was renal toxicity.</li><li>8.Other major toxicities of cisplatin in animals included myelosuppression, gastro-intestinal, hepatic and ototoxicity.</li></ul> <h3>Clinical</h3> (a) <i>Efficacy</i> Cisplatin has demonstrated antitumor activity as a single agent and in combination with other antitumor drugs in the following metastatic tumors.<ul>o<li>1.Testicular cancer—An active drug combination included cisplatin (20 mg/m² daily × 5 or 120 mg/m² single dose), bleomycin, vinblastine with the addition of cyclo-phosphamide and actinomycin D in some regimens. Complete response rates of 60–70% have been reported and the survival times of these patients have been significantly increased over patients receiving other therapy.</li><li>2.Ovarian cancer—Cisplatin has shown activity in ovarian cancer as single agent (50–100 mg/m²) and in combination with adriamycin. Survival times of complete responders have been significantly increased over those obtained with standard alkylating agent therapy.</li><li>3.Other adult tumors—Cisplatin has demonstrated activity as a single agent and in combination chemotherapy in metastatic tumors of the urinary bladder, cervix, head and neck, and prostate.</li><li>4.Pediatric tumors—Antitumor activity of cisplatin has been observed in pediatric patients with osteogenic sarcoma and neuroblastoma.</li></ul> (b) <i>Toxicity</i><ul>o<li>1.Renal toxicity—Dose related and cumulative renal insufficiency was the major dose-limiting toxicity of cisplatin. It was first noted during the second week after a dose of cisplatin.</li><li>2.Hematologic—Cisplatin-induced myelosuppression was dose related and occurred in approximately 25–30% of patients treated. The nadirs in circulating platelets and leukocytes occurred between days 18–23 after a dose of cisplatin.</li><li>3.Ototoxicity—Dose related and cumulative ototoxicity has been associated with cisplatin therapy. This toxicity was manifested by loss of hearing in the high frequency range (4000–8000 Hz).</li><li>4.Nausea and Vomiting—Nearly all patients treated with cisplatin have experienced nausea and vomiting. In most cases antiemetics have been ineffective in controlling emesis.</li><li>5.Other toxicities—Ncurotoxicity, characterized by peripheral neuropathies, hyperuricemia and anaphylactic-like reactions have been reported to occur infrequently after cisplatin administration. Neurotoxicity appeared to be total dose related.</li></ul> (c) <i>Mode of administration</i> Three modes of cisplatin administration have significantly reduced the incidence and severity of renal toxicity.<ul>o<li>1.Patients received intravenous hydration with 1 to 21 of saline for 8 to 12 h prior to a 15 min intravenous infusion of cisplatin in saline and followed by saline hydration for 24 h.</li><li>2.Patients received intravenous hydration with 21 of 5% glucose in 0.5 n-saline, and 12.5 g mannitol immediately prior to a 10–15 min infusion of cisplatin followed by a continuous infusion of 10 g/h mannitol in 0.5 n-saline over the next 6 h.</li><li>3.Patients received cisplatin mixed with 37.5 g mannitol and 40 mg furosemide administered as an intravenous infusion with 2 1 of 5% dextrose in 0.33 n-saline for 6 to 8 h. Patients received subsequent hydration to replace fluids lost as a result of emesis and diuresis.</li></ul>