bluuebunny/crossref_metadata_2025 huggingface dataset:
Spectroscopic Studies of Copper, Silver and Gold‐Metallothioneins
Authors: Stillman Martin J. , Presta Anthony , Gui Ziqi , Jiang De-Tong
Published: March 2007

Metallothionein is a ubiquitous protein with a wide range of proposed physiological roles, including
the transport, storage and detoxification of essential and nonessential trace metals. The amino
acid sequence of isoform 2a of rabbit liver metallothionein, the isoform used in our spectroscopic
studies, includes 20 cysteinyl groups out of 62 amino acids. Metallothioneins in general represent
an impressive chelating agent for a wide range of metals. Structural studies carried out by a
number of research groups (using  1H and  113Cd NMR, X‐ray crystallography, more recently EXAFS,
as well as optical spectroscopy) have established that there are three structural motifs for metal
binding to mammalian metallothioneins. These three structures are defined by metal to protein
stoichiometric ratios, which we believe specifically determine the coordination geometry adopted
by the metal in the metal binding site at that metal to protein molar ratio. Tetrahedral geometry is
associated with the thiolate coordination of the metals in the M7‐MT species, for M = Zn(II), Cd(II),
and possibly also Hg(II), trigonal coordination is proposed in the M11-12‐MT species, for M = Ag(I),
Cu(I), and possibly also Hg(II), and digonal coordination is proposed for the metal in the M17-18‐MT
species for M = Hg(II), and Ag(I). The M7‐MT species has been completely characterized for M =
Cd(II) and Zn(II).  113Cd NMR spectroscopic and x‐ray crystallographic data show that mammalian
Cd7‐MT and Zn7‐MT have a two domain structure, with metal‐thiolate clusters of the form
(the α domain) and (the β domain). A similar two domain structure involving
(α) and (β) copper‐thiolate clusters has been proposed for the Cu12‐MT species.
Copper‐, silver‐ and gold‐containing metallothioneins luminesce in the 500‐600 nm region from
excited triplet, metal‐based states that are populated by absorption into the 260‐300 nm region of
the metal‐thiolate charge transfer states. The luminescence spectrum provides a very sensitive
probe of the metal‐thiolate cluster structures that form when Ag(I), Au(I), and Cu(I) are added to
metallothionein. CD spectroscopy has been used in our laboratory to probe the formation of
species that exhibit well‐defined three‐dimensional structures. Saturation of the optical signals
during titrations of MT with Cu(I) or Ag(I) clearly show formation of unique metal‐thiolate structures
at specific metal:protein ratios. However, we have proposed that these M=7, 12 and 18 structures
form within a continuum of stoichiometries. Compounds prepared at these specific molar ratios
have been examined by X‐ray Absorption Spectroscopy (XAS) and bond lengths have been
determined for the metal‐thiolate clusters through the EXAFS technique. The stoichiometric ratio
data from the optical experiments and the bond lengths from the XAS experiments are used to
propose structures for the metal‐thiolate binding site with reference to known inorganic
metal‐thiolate compounds.
The Cellular Metabolism and Effects of Gold Complexes
Authors: Graham Garry G. , Champion G. David , Ziegler John B.
Published: March 2007

Leads to the cellular effects of the anti‐arthritic gold complexes may come from
the determination of their metabolism by target cells and, possibly, cells in the immediate
environment of the target cells. Polymorphonuclear leukocytes (PMN) and mononuclear cells
(monocytes and lymphocytes) are present in inflamed joints of patients with rheumatoid arthritis and
these cells have been widely used in pharmacological studies on the gold complexes. It is
suggested that the cellular effects of the gold complexes are mediated by the production of
aurocyanide. According to this hypothesis, PMN metabolize small quantities of thiocyanate to
cyanide which, in turn, converts gold complexes, such as aurothiomalate, to aurocyanide
(dicyanogold(I)) which inhibits the functions of PMN and other cells. There is now considerable
evidence for this hypothesis from in vitro studies but there is little in vivo work to back up the
hypothesis. One of the few in vivo studies which tested the hypothesis involved the examination
of the activity of aurothiomalate in the treatment of polyarthritis in Hooded Wistar rats. Activity of
aurothiomalate is only shown in animals which received thiocyanate. Hydrogen cyanide is a
constituent of cigarette smoke and the aurocyanide formed by the interaction with gold complexes
and inhaled hydrogen cyanide rapidly diffuses into red blood cells. Because of the metabolism of
hydrogen cyanide to thiocyanate in the liver, there are higher plasma levels of thiocyanate in
smokers than in non‐smokers. Smokers may have a greater incidence of side effects than non‐smokers
but there appears to be little difference in therapeutic response, possibly because there is
sufficient thiocyanate in extracellular fluid, even in non‐smokers, to support the conversion of gold
complexes to aurocyanide. The relationship between the metabolism and effects of the orally
active gold complex, auranofin are less clear. Auranofin itself is taken up by cells with the loss of the
ligands bound to gold while its inhibitory activity against the oxidative burst of PMN decreases with
increasing cell density. For example, the lucigenin‐dependent chemiluminescence of 106 PMN/ml
is 46 percent of control at 0.5 μM auranofin but only 2.2 percent in 2.105 PMN/ml in the presence
of the same concentration of auranofin. A potentially active gold complex is a plasma component
which is taken up by red blood cells.
Electronic and Steric Effects in Gold(I) Phosphine ThiolateComplexes
Authors: Foley Janet , Fort Raymond C. , McDougal Katherine , Bruce Mitchell R. M. , Bruce Alice E.
Published: March 2007

The unusual yellow color of Au2(dppm)(SR) 2 (R = 4‐tolyl; dppm = diphenylphosphinomethane) is
attributed to a red‐shift in the S→Au charge transfer caused by destabilization of the sulfur highest
occupied molecular orbital (HOMO). Variable temperature experiments show two broad bands at
‐80°C in the  31P{ 1H} NMR spectrum of Au2(dppm)(SR) 2 and the activation energy for
interconversion is 10 kcal/mol. Only one sharp band is observed down to ‐80°C in the spectrum of
the white complex, Au2(dppe)(SR) 2 (dppe = diphenylphosphinoethane). Molecular mechanics
calculations on Au2(dppm)(SR) 2 and Au2(dppe)(SR) 2 reveal that, for Au2(dppe)(SR) 2, a series of
maxima and minima, separated by 2.5 kcal/mol, occur every 120° which is consistent with rotation
around an unhindered carbon‐phosphorus single bond. The Au atoms are not within bonding
distance in any conformation. Computational results for Au2(dppm)(SR) 2 indicate one minimum
energy structure in which the Au‐P bonds are anti. There is a high energy conformation (9 kcal/mol
above the global minimum) where overlap between golds is maximized. The implications of
gold‐gold bonding in this complex are discussed. The steric influence of the thiolate ligand has
been examined by synthesizing a series of dinuclear gold(I) complexes in which the steric
properties of the thiolate are varied: Au2(dppm)(SR) 2 (R = 2,6‐dichlorophenyl; 2,6‐dimethylphenyl;
3,5‐dimethylphenyl). The 2,6‐disubstituted complexes are white, while the 3,5‐dimethyl complex is
yellow. These results, along with VT‐NMR experiments, are consistent with the conclusion that the
more sterically‐bulky thiolates hinder the close approach of the golds in the dinuclear complexes.
Water‐Soluble Ruthenium(III)‐Dimethyl Sulfoxide Complexes:Chemical Behaviour and Pharmaceutical Properties
Authors: Mestroni G. , Alessio E. , Sava G. , Pacor S. , Coluccia M. , Boccarelli A.
Published: March 2007

In this paper we report a review of the results obtained in the last few years by our
group in the development of ruthenium(III) complexes characterized by the presence of
sulfoxide ligands and endowed with antitumor properties. In particular, we will focus on
ruthenates of general formula Na[trans‐RuCl4(R1R2SO)(L)], where R1R2SO =
dimethylsulfoxide (DMSO) or tetramethylenesulfoxide (TMSO) and L = nitrogen donor
ligand. The chemical behavior of these complexes has been studied by means of
spectroscopic techniques both in slightly acidic distilled water and in phosphate buffered
solution at physiological pH. The influence of biological reductants on the chemical
behavior is also described. The antitumor properties have been investigated on a number
of experimental tumors. Out of the effects observed, notheworthy appears the capability
of the tested ruthenates to control the metastatic dissemination of solid metastasizing
tumors. The analysis of the antimetastatic action, made in particular on the MCa
mammary carcinoma of CBA mouse, has demonstrated a therapeutic value for these
complexes which are able to significantly prolong the survival time of the treated
animals. The antimetastatic effect is not attributable to a specific cytotoxicity for
metastatic tumor cells although in vitro experiments on pBR322 double stranded DNA
has shown that the test ruthenates bind to the macromolecule, causing breaks
corresponding to almost all bases, except than thymine, and are able to cause interstrand
bonds, depending on the nature of the complex being tested, some of which results active
as cisplatin itself.
Redox Chemistry of Gold(I) Phosphine Thiolates: Sulfur‐BasedOxidation
Authors: Jiang Tong , Wei Gang , Turmel Cristopher , Bruce Alice E. , Bruce Mitchell R. M.
Published: March 2007

The redox chemistry of mononuclear and dinuclear gold(I) phosphine arylthiolate complexes
was recently investigated by using electrochemical, chemical, and photochemical techniques. We
now report the redox chemistry of dinuclear gold(I) phosphine complexes containing aliphatic
dithiolate ligands. These molecules differ from previously studied gold(I) phosphine thiolate
complexes in that they are cyclic and contain aliphatic thiolates. Cyclic voltammetry experiments of
Au2(LL)(pdt) [pdt = propanedithiol; LL = 1,2‐bis(diphenylphosphino)‐ethane (dppe),
1,3‐bis(diphenylphosphino)propane (dppp), 1,4‐bis(diphenylphosphino)butane (dppb),
1,5‐bis(diphenylphosphino)pentane (dpppn)] in 0.1 M TBAH/CH3CN or CH2Cl2 solutions at 50 to
500 mV/sec using glassy carbon or platinum electrodes, show two irreversible anodic processes at
ca. +0.6 and +1.1 V (vs. SCE). Bulk electrolyses at +0.9 V and +1.4 V result in n values of 0.95
and 3.7, respectively. Chemical oxidation of Au2(dppp)(pdt) using one equivalent of Br2
(2 oxidizing equivalents) yields 1,2‐dithiolane and Au2(dppp)Br2. The reactivity seen upon mild
oxidation ≤ +1.0 V is consistent with formal oxidation of a thiolate ligand, followed by a fast
chemical reaction that results in cleavage of a second gold‐sulfur bond. Oxidation at higher
potentials (≥ +1.3 V) is consistent with oxidation of gold(I) to gold(III). Structural and
electrochemical differences between gold(I) aromatic and aliphatic thiolate oxidation processes are
discussed.
Stimulation, Recording Potential and Antimicrobial Medical Catheter Coatings
Authors: Beard Richard B. , DeLaurent Mark , Pourrezaei Kambiz , Adrian Sorin
Published: March 2007

Biocompatibility of electrodes for stimulation are difficult to maintain
homeostasis. Noble metal stimulating electrodes which are normally
biocompatible on keratinized tissue become very non‐biocompatible when they
are interfaced with nonkeratinized tissue in an area such as the oral cavity.
Composite electrodes have been made biocompatible in the oral cavity even at
current densities larger than 1 μA/mm2. Electrodes used in potential readings
require that the anodic and cathodic polarization remain minimal. Silver‐silver
chloride electrodes are minimal. Silver‐silver chloride electrodes are not always
reversible. The range of pH, voltages and current densities when silver‐silver
chloride are not reversible are presented. Recently at Drexel University reliable
silver coatings inside and outside of medical catheters have been fabricated to act
as antimicrobial to a variety of bacteria. Noble and nonnoble metals have been
combined in coatings with silver to enhance the antimicrobial action.
Excited States of Gold(I) Compounds, Luminescence and Gold‐Gold Bonding
Authors: Fackler John P. , Assefa Zerihun , Forward Jennifer M. , Staples Richard J.
Published: March 2007

It has long been established by Khan that the superoxide anion, , generates singlet oxygen, ,
during dismutation. Auranofin, gold‐phosphine thiols, β‐Carotene, and metal‐sulfur compounds can
rapidly quench singlet O2. The quenching of the , which exists at 7752 cm-1 above the ground state
triplet, may be due to the direct interaction of the singlet O2 with gold(I) or may require special ligands
such as those containing sulfur coordinated to the metal. Thus we have been examining the excited state
behavior of gold(I) species and the mechanisms for luminescence. Luminescence is observed under
various conditions, with visible emission ranging from blue to red depending on the ligands coordinated
to gold(I). Triplet state emission can be found from mononuclear three coordinate Au(I) species, including
species which display this behavior in aqueous solution. A description is given of the luminescent three
coordinate TPA (triazaphosphaadamantane) and TPPTS (triphenylphosphine‐trisulfonate) complexes,
the first examples of water soluble luminescent species of gold(I).
Antibacterial Silver
Authors: Clement Julia L. , Jarrett Penelope S.
Published: March 2007

The antibacterial activity of silver has long been known and has found a variety of applications
because its toxicity to human cells is considerably lower than to bacteria. The most widely
documented uses are prophylactic treatment of burns and water disinfection. However, the
mechanisms by which silver kills cells are not known. Information on resistance mechanisms is
apparently contradictory and even the chemistry of Ag+ in such systems is poorly understood.

Silver binds to many cellular components, with membrane components probably being more
important than nucleic acids. It is difficult to know whether strong binding reflects toxicity or
detoxification: some sensitive bacterial strains have been reported as accumulating more silver than
the corresponding resistant strain, in others the reverse apparently occurs. In several cases
resistance has been shown to be plasmid mediated. The plasmids are reported as difficult to
transfer, and can also be difficult to maintain, as we too have found. Attempts to find biochemical
differences between resistant and sensitive strains have met with limited success: differences are
subtle, such as increased cell surface hydrophobicity in a resistant Escherichia coli.

Some of the problems are due to defining conditions in which resistance can be observed. Silver(I)
has been shown to bind to components of cell culture media, and the presence of chloride is
necessary to demonstrate resistance. The form of silver used must also be considered. This is
usually water soluble AgNO3, which readily precipitates as AgCl. The clinically preferred compound
is the highly insoluble silver sulfadiazine, which does not cause hypochloraemia in burns. It has
been suggested that resistant bacteria are those unable to bind Ag+ more tightly than does
chloride. It may be that certain forms of insoluble silver are taken up by cells, as has been found for
nickel. Under our experimental conditions, silver complexed by certain ligands is more cytotoxic than
AgNO3, yet with related ligands is considerably less toxic. There is evidently a subtle interplay of
solubility and stability which should reward further investigation.
The Antirheumatic Drug Gold, a Coin With Two Faces: AU(I) and AU(III).Desired and Undesired Effects on the Immune System
Authors: Takahashi Kazuo , Griem Peter , Goebel Carsten , Gonzalez Jose , Gleichmann Ernst
Published: March 2007

Three new findings are reviewed that help to understand the mechanisms of
action of antirheumatic Au(I) drugs, such as disodium aurothiomalate (Na2Au(I)TM):
(i) We found that Na2Au(I)TM selectively inhibits T cell receptor (TCR)‐mediated
antigen recognition by murine CD4+ T cell hybridomas specific for antigenic peptides
containing at least two cysteine residues. Presumably, Au(I) acts as a chelating
agent forming linear complexes (Cys‐Au(I)‐Cys) which prevent correct antigen‐processing
and/or peptide recognition by the TCR. (ii) We were able to show that
Au(I) is oxidized to Au(III) in phagocytic cells, such as macrophages. Because Au(III)
is re‐reduced to Au(I) this may introduce an Au(I)/Au(III) redox system into phagocytes
which scavenges reactive oxygen species, such as OCl- and inactivates
lysosomal enzymes. (iii) Pretreatment with Au(III) of a model protein antigen, bovine
ribonuclease A (RNase A), induced novel antigenic determinants recognized by
CD4+ T lymphocytes. Analysis of the fine specificity of these ‘Au(III)‐specific’ T cells
revealed that they react to RNase peptides that are not presented to T cells when the
native protein, i.e., not treated with Au(III), is used as antigen. The T cell recognition
of these cryptic peptides did not require the presence of gold. This finding has
important implications for understanding the pathogenesis of allergic and autoimmune
responses induced by Au(I) drugs. Taken together, our findings indicate that
Au(I) and Au(III) each exert specific effects on several distinct components of
macrophages and the subsequent activation of T cells; these effects may explain
both the desired anti‐inflammatory and the adverse effects of antirheumatic gold
drugs.
Synthesis, Structure and Biological Activity of 6‐R3Si(Ge, Sn)‐Substituted 5‐Fluorouracils
Authors: Lukevics E. , Ignatovich L. , Shilina N. , Kemme A. , Sjakste N.
Published: March 2007

Direct lithiation of 1‐(2‐tetrahydrofuryl)‐5‐fluorouracil (Ftorafur) has been investigated. The treatment
of ftorafur with lithium diisopropylamide (LDA)at –70℃ in ether‐hexane, followed by the reaction
with various electrophiles afforded the corresponding 6‐substituted silicon, germanium and tin
derivatives of ftorafur. The results of biological investigation indicate the ability of germanium–modified
nucleoside analogues to interfere with transcription and replication processes.
The Anti‐Inflammatory Activityof Boron Derivatives in Rodents
Authors: Hall Iris H. , Burnham Bruce S. , Chen Shang Y. , Sood Anup , Spielvogel Bernard F. , Morse Karen W.
Published: March 2007

Acyclic amine‐carboxyboranes were effective anti‐inflammatory agents in mice at 8 mg/kg x 2.
These amine‐carboxyboranes were more effective than the standard indomethacin at 8 mg/kg x
2, pentoxifylline at 50 mg/kg x 2, and phenylbutazone at 50 mg/kg x 2. The heterocyclic amine
derivatives as well as amine‐carbamoylboranes, carboalkoxyboranes, and cyanoboranes were
generally less active. However, selected aminomethyl‐phosphonate‐N‐cyanoboranes
demonstrated greater than 60% reduction of induced inflammation. The boron compounds were
also active in the rat induced edema, chronic arthritis, and pleurisy screens, demonstrating
activity similar to the standard indomethacin. The compounds were effecive in reducing local
pain and decreased the tail flick reflex to pain. The derivatives which demonstrated good anti‐inflammatory
activity were effective inhibitors of hydrolytic lysosomal, and proteolytic enzyme
activities with IC50
values equal to 10-6M
in mouse macrophages, human leukocytes, and Be
Sal osteofibrolytic cells. In these same cell lines, the agents blocked prostaglandin
cyclooxygenase activity with IC50 values of 10-6M. In mouse macrophage and human
leukocytes, 5′ lipoxygenase activity was also inhibited by the boron derivatives with IC50 values
of 10-6M. These IC50 values for inhibition of these enzyme activities are consistent with
published values of known anti‐inflammatory agents which target these enzymes.
Structural Characterization of the Rhenium(V) Oxo Complex of Mercaptoacetyltriglyclne in its Dianionic Form
Authors: Hansen Lory , Taylor Andrew , Marzilli Luigi G.
Published: March 2007

Dianionic (MAG3=
penta‐anionic form of mercaptoacetyltriglycine, M =  186Re, 99mTc
)
complexes have important applications in nuclear medicine. In vivo the complexes have a
deprotonated carboxyl group that is important to their biodistribution. The solid‐state structures of
 99Tc
and Re complexes with mercaptoacetyltriglycine reported previously are monoanions with
protonated carboxyl groups. In the present work, we report the preparation and X‐ray crystal
structure of Na2[ReO(MAG3)] · 5H2O(1), which contains the physiologically relevant dianion. The
dianion is a distorted square pyramid with the nitrogen and sulphur donor atoms forming the base
and the oxo ligand at the apex. The terminal carboxyl group is deprotonated, uncoordinated and
has a syn orientation with respect to the oxo ligand. The syn conformation of the dianion in 1 differs
in conformation from the anti‐monoanion in [Bu4N][ReO(MAG3H)]
but is similar to the syn‐monoanion in [Ph4P][ 99TcO(MAG3H)]
.
A Spectroscopic Study on PtCl4(2−) Binding to Rabbit SkeletalMuscle G‐Actin
Authors: Zou Juan , Sun Hong-Ye , Wang Kui
Published: March 2007

It was found that the binding of
to G‐actin and the consequent conformational
changes are different with those for hard acids. It is a two‐step process depending on molar
ratio /actin (R). In the first step, R less than 25, the ions are bound to
sulfur‐containing groups preferentially. These high‐affinity sites determined by Scatchard
approach are characterized by n1 = 30
with average binding constant K1=1.0×107M−1. The
conformational changes are significant as characterized by N‐(1‐pyrenyl) maleimide(NPM)
labeled fluorescence, intrinsic fluorescence and CD spectra. EPR spectroscopy of
maleimide spin labeled(MSL) actin demonstrated that even binding is limited to a
very small fraction of high‐affinity sites(R<1), it can bring about a pronounced change of
conformation. In the range of R=25‐40, high‐affinity sites accessible are saturated. In the
second step(R>40)
, deep‐buried binding sites turn out to be accessible as a result of the
accumulated conformational changes. These new binding sites are estimated to be n2=26
with average binding constant K2=2.1×106M-1. Although in this step the quenching of
intrinsic fluorescence goes on and the NPM‐labled thiols moves to more hydrophilic
environment, no change in α‐helix content was found. These results suggested that with
increasing in binding, the G‐actin turns to an open and loose structure in a
discontinuous mode.
Structure Determination and Anti‐Inflammatory Activity of somePurine Complexes
Authors: Marwaha Satwinder S. , Kaur Jasjest , Sodhi Gurvinder S.
Published: March 2007

Organomercury(II)‐purine derivatives of the type, p‐MeOC6H4HgL1 (I), p‐NO2C6H4HgCl(L2)
(II), p‐MeC6H4HgCl(L3)(III) and p‐NO2C6H4HgCl(L3) (IV) [HL1 = theophylline, L2 = theobromine, L3 =
caffeine] have been synthesised and characterised on the basis of spectral studies (IR, UV,  1H &  13C NMR). The complexes have been screened for anti‐inflammatory activity.
UVA‐Photosensitivityof cis‐Diamminedichloro‐Platinum(II)‐Modified DNA
Authors: Payet Dominique , Leng Marc
Published: March 2007

cis‐Diamminedichloroplatinum(II)‐modified oligonucleotides contain‐ing either a single
intrastrand cross‐link at the d(GpG) site or an interstrand cross‐link at the d(GpC/GpC) site, were
irradiated with 320 to 400‐nm light. Upon irradiation, the adducts are photosensitive. Among the
photo‐induced reactions, the cleavage of the coordination bonds between platinum and the G
residues in the interstrand cross‐link is demonstrated.
Use of Organosilicon Compounds towards the Rational Design ofAntiparasitic and Antiviral Drugs
Authors: Déléris Gérard
Published: March 2007

One of the major problems met for the conception of antiviral or antiparasitic drugs is to
reach a high level of selectivity towards the pathogenic agent versus the host. We shall describe
two synthetic approaches where main group organometallics have been used towards this goal. A
series of nucleoside sila‐analogues was synthesized as potential therapeutic agents designed to
inhibit HIV Reverse Transcriptase. In a second approach novel organosilicon derivatives have
been synthesized as mimics of antisense oligonucleotides.

Infectious agents, namely viruses or parasites, more or less use cellular machinery. Therefore
therapeutic agents must interfere with biochemical mechanisms or possess high affinity towards
specific molecular cellular components, to reach selectivity.

We thought that main group organometallics could show many advantages for designing
biologically active molecules in this field. They allow a high synthetic flexibility for the modulations
of physico‐chemical properties and they show a mechanistic behaviour which may be close to the
one of several heteroelements present in living organisms such as sulfur or phosphorus.

We tried to use this approach towards two directions involving the synthesis of organosilicon
derivatives i.e:

‐the synthesis of organosilicon derivatives as inhibitors of HIV Reverse Transcriptase,

‐the synthesis of organosilicon precursors of modified antisense oligonucleotides.
On the Mechanism of Action of the Antitumor Drug cis‐Platin(cis‐DDP) and its Second Generation Derivatives
Authors: Aletras Vasilis , Hadjiliadis Denis , Hadjiliadis Nick
Published: March 2007

The present article attempts to summarise the elements of the
mechanism of action of the antitumor drug ‐Platin presented the last few
years. Highlights on the discovery, of the drug and the development of it’s
second generation derivatives are presented, as well as the ways that
‐DDP reacts with biomolecules as DNA and proteins and their models e.g.
nucleosides, nucleotides. Also the hydrolysis data are presented for
‐DDP and its’ inactive congener ‐DDP, as well as for the second
generation drug carboplatin. Finally, usefull conclusions are given from
this work, pointing out the unanswered questions about the action of ‐DDP as well as its differences in action, in comparison with ‐DDP.
Cytotoxic Phosphinoarsino and Diphosphino Pd(II) Complexesof Thiolate Amino Acids and Glutathione
Authors: Dhubhghaill Orla M. Ni , Sadler Peter J. , Fernandez Esther Garcia
Published: March 2007

The novel complexes [Pd(L‐L′)(SR)Cl] where L‐L′ is Ph2PCH2CH2PPh2
(dppe) or
Ph2AsCH2CH2PPh2
(dadpe) and RSH is glutathione, L‐cysteine, or N‐acetyl‐L‐cysteine, have
been prepared and characterised. Their structures in the solid‐state and in solution are
discussed. The introduction of cysteine or glutathione as a ligand in these complexes greatly
improved their aqueous solubility compared with the hydrophobic parent dichloro complexes. The
cytotoxicities of the glutathione complexes towards the cell‐lines L1210, ADJ/PC6 and CH1 were
investigated. Their cytotoxicities towards L1210 cells were comparable to those of the parent
dichloro complexes.
Synthesis, Structure and Antitumour Properties of a New1,2‐Propylenediaminetetraacetate‐Ruthenium(III) Compound
Authors: Vilaplana R. , Romero M. A. , Quirós M. , Salas J. M. , González-Vílchez F.
Published: March 2007

A novel complex formed by ruthenium (III) and the sequestering ligand
1,2‐propylenediaminetetraacetic acid (PDTA) has been synthetized and characterized. The structure
of the monomeric compound, studied by X‐ray diffraction , shows an almost symmetric octahedral
geometry around the metal ion, with two chlorine atoms in a cis conformation. The antitumour
activity against a variety of murine and human cancers is reported.
Hypolipidemic Activity of Amine‐Borane Aducts of Cyclohexylamineand Toluidine in Rodents
Authors: Burnham Bruce S. , Chen S. Y. , Sood A. , Spielvogel Bernard F. , Hall Iris H.
Published: March 2007

The amine‐borane adducts of cyclohexylamine and toluidine were observed
to be potent hypolipidemic agents in mice, I.P. and rats orally at 8
mg/kg/day lowering both serum cholesterol and triglyceride levels after
14‐16 days. These compounds were able to lower tissue lipids including
the cholesterol content of the aorta wall. The agents successfully
lower VLDL‐ and LDL‐cholesterol content while elevating HDL‐cholesterol
content significantly. The agents also modulate lipid regulatory enzyme
activities in a manner to reduce liver lipid levels. These studies
demonstrate that the nitrogen atom does not have to be apart of the
aromatic ring as in heterocyclic‐amine borane to afford good
hypolipidemic activity in rodents.
Spectral Studies and Bactericidal, Fungicidal, Insecticidal andParasitological Activities of Organotin(IV) Complexes of ThioSchiff Bases Having no Donor Atoms
Authors: Nath Mala , Goyal Savita
Published: March 2007

Twelve new organotin(IV) complexes of the type RnSnLm
[where n = 3, m = 1, R = CH3
or
C6H5 ;
n = 2, m = 2, R = C6H5 or C4H9 ; L = anion of Schiff bases derived from the condensation
of 2‐amino‐5‐(o
‐anisyl)‐l,3,4‐thiadiazole with salicylaldehyde (HL‐1), 2‐
hydroxynaphthaldehyde (HL‐2) and 2‐hydroxyacetophenone (HL‐3)] have been synthesized and
characterized by elemental analysis, molar conductances, electronic, infrared, far‐infrared,  1H
NMR
and  119Sn
Mössbauer spectral studies. Thermal studies of two complexes, viz., Ph3Sn
(L‐1) and
Ph2Sn(L‐2) 2
have been carried out in the temperature range 25‐1000∘C
using TG, DTG and DTA
techniques. All these complexes decompose gradually with the formation of SnO2
as an end product.
In vitro antimicrobial activity of the Schiff bases and their complexes has also been determined
against Streptococcus faecalis, Klebsiella pneumoniae, Escherichia coli, Pseudomonas aeruginosa,
Staphylococcus aureus Penicillin resistance (2500 units), Candida albicans, Cryptococcus
neoformans, Sporotrichum schenckii, Trichophyton mentagrophytes and Aspergillus fumigatus. The
Schiff bases (HL‐1), (HL‐2) and the organotin(IV) compounds have also been tested against various
important herbicidal, fungicidal, insecticidal species and also for parasitological activity against
freeliving nematode.
Synthesis, Structure of Nitrogen‐ContainingPhosphinogold(I) Ferrocenes. In vitro Activity against Bladder andColon Carcinoma Cell Lines
Authors: Viotte Manuella , Gautheron Bernard , Kubicki Marek M. , Nifant′ev Ilya E. , Fricker Simon P.
Published: March 2007

The gold salt [(tht)AuCl] was reacted with [1‐N,N‐dimethylaminométhyl‐2‐diphenylphosphino]ferrocene (1) forming the bimetallic derivative 4. The reaction of methyl iodide
and tetramethylammonium bromide on the chloride 4 produced the ammonium salt 5 and the
bromide 6 respectively. New aminophosphines 2 and 3, which represent two of the rare
phosphorylated metallocenes containing P(III)‐N bond have also been coordinated to gold(I) to
form 7 and 8. The presence of the ethoxy group in 7 provides evidence for the lability of one
nitrogen‐phosphorus bond. The X‐ray structure of compounds 4 and 7 have been established.
Both crystallize in space group P21/c, monoclinic, with a = 11.095(2) Å, b = 12.030(3) Å, c =
17.763(4) Å, β= 94.02(2)∘, Z = 4 for 4 and a = 14.863(3) Å, b = 8.036(5)Å, c = 18.062(5)Å, β
=101.64(1)°, Z = 4 for 7.  197Au
Mössbauer data are in good agreement with those for other linear P‐Au‐Cl containing complexes. The compounds were evaluated for in vitro anti‐tumour activity
against two human tumours. Differential cytotoxicity was observed with activity comparable to
cisplatin, with the exception of one compound which was significantly more cytotoxic.
Synthesis, Characterization and In vitro Antitumour Activityof Novel Organotin Derivatives of 1,2‐ and1,7‐Dicarba‐Closo‐dodecaboranes
Authors: Gielen Marcel , Kayser François , Zhidkova Olga B. , Kampel Vladimir Ts. , Bregadze Vladimir l. , de Vos Dick , Biesemans Monique , Mahieu Bernard , Willem Rudolph
Published: March 2007

Several organotin derivatives of 1,2‐ and 1,7‐dicarba‐closo‐dodecaboranes were
synthesized and characterized by  119Sn
Mössbauer,  1H
,  13C
and  119Sn
NMR spectroscopy.
Their antitumour activities in vitro against cancerous cell lines of human origin are reported.
Effects of Cisplatin and its Analogues on the Permeabilityof Human Erythrocyte Membrane
Authors: Lu J.-F. , Wang K. , Sun X.-Z. , Xing F. , An P.-D. , Yang Z.-H. , Yin J.-J.
Published: March 2007

The biomembrane is postulated as the initial target when Platinum(II) complexes
attack cells. In this work, a spin‐labeling ESR technique has been used to study the effects
of cis‐DCDP, cis‐DBDP, cis‐DIDP, trans‐DCDP, and cis‐DADP on the permeability of
human erythrocyte membrane. We monitored the reduction processes of the ESR signal of
a nitroxide spin label, (TEMPO), which leaks out through the membrane and is reduced by
the external ascorbate. Our results indicate that cisplatin and its analogues can enhance the
permeability of membranes to small moieties such as TEMPO and ascorbate, and the
differences between these compounds are related to features of the leaving group. In
addition, changes in the order parameter of 5DS spin label in membrane indicate that
hydrolysis of these Pt(II) complexes result in membrane damage.
Cytotoxicity and Antineoplastic Activities of Alkylamines andTheir Borane Derivatives
Authors: Hall Iris H. , Tse Elaine Y. , Muhammad Rosallah A.
Published: March 2007

The alkylamines and their related boron derivatives demonstrated potent
cytotoxicity against the growth of murine and human tissue cultured
cells. These agents did not necessarily require the boron atom to
possess potent cytotoxic action in certain tumor lines. Their ability
to suppress tumor cell growth was based on their inhibition of DNA and
protein syntheses. DNA synthesis was reduced because purine synthesis
was blocked at the enzyme site of IMP dehydrogenase by the agents. In
addition ribonucleotide reductase and nucleoside kinase activities were
reduced by the agents which would account for the reduced d[NTP] pools.
The DNA template or molecule may be a target of the drugs with regard to
binding of the drug to nucleoside bases or intercalaction of the drug
between DNA base pairs. Only some Of the agents caused DNA
fragmentation with reduced DNA viscosity. These effects would
contribute to overall cell death afforded by the agents.
Complexes of Zinc With Picolinic and Aspartic Acids Inactivate Free Varicella‐Zoster Virions
Authors: Shishkov S. , Varadinova T. , Bontchev P. , Nachev C. , Michailova E.
Published: March 2007

Zn(II) picolinate and aspartate, Zn(pic) 2 and Zn(asp) 2, have been shown to inhibit key steps of the
replication of HSV‐1. In the present study we describe the effect of Zn(pic) 2 and Zn(asp) 2 on the
replication of VZV and on the infectivity of free virions. The experiments are done using BHK‐21
cells, a clinical isolate of VZV and Zn‐complexes in concentration of 10 μM. When Zn‐complexes
are present during the whole period of infection, the yield of infectious virus progeny decreases up
to 98%. The infectivity of VZV is completely restored after the removal of zinc. The virucidal effect is
manifested at the 2nd h of contact, when 90% of the virions are inactivated. The results show that
both Zn(pic) 2 and Zn(asp) 2 specifically inactivate free VZV virions with no effect on viral replication.
New Perfluorophtalate Complexes of Platinum(II) With Chemotherapeutic Potential
Authors: de Oliveira M. B. , Miller J. , Banks R. E. , Kelland L. R. , McAuliffe C. A. , Mahmood N. , Rowland I. J.
Published: March 2007

Two new platinum(II) complexes have been synthesized and their anti‐tumour and anti‐HIV activities have
been evaluated.

The new complexes are: (i) cis‐tetrafluorophthalate‐ammine‐morpholine‐platinum(II) or MMF3 and (ii) cis‐tetrafluorophthalate‐
ammine‐piperidine‐platinum(II) or MPF4. They were characterized by elemental analysis,
IR spectra and  1H and  13C NMR spectra.

They were tested against five human ovarian carcinoma cell lines, viz., CH1, CH1cisR, A2780, A2780cisR
and SKOV‐3. They were less active than cis‐platin and showed cross‐resistance with cis‐platin in the
CH1cisR and A2780cisR acquired resistance lines.

They were also tested for possible anti‐HIV activity using the HIV‐I IIIB virus and C8166 cells, but they
were inactive compared with AZT.
"In Vivo" Effects of Lithium Sulphate on the Turnover of Rat TissueNucleotides
Authors: Loghin Felicia , Socaciu Carmen , Leucuta Sorin E.
Published: March 2007

The effects of lithium sulphate following acute administration to Wistar rats ‐ in therapeutic and toxic
doses ‐ were investigated, using as markers the levels and turnover of brain, kidney and liver
nucleotides. Adenine‐ and guanine‐dependent nucleotides were assayed concomitantly, using a high‐
performance liquid chromatographic method. Following acute administration, lithium′s effects on 3’,5’‐
cAMP levels were more significant at hepatic and cerebral level, in a dose‐dependant manner. The
effect on 3’,5’‐cGMP had tissue specificity and was not dose‐dependant. It might be possible that 3’,5’‐cGMP is a better indicator of lithium toxicity than 3’,5’‐cAMP.
Extent of the Acidification by N7‐Coordinatedcis‐Diammine‐Platinum(II) on the Acidic Sites of Guanine Derivatives
Authors: Song Bin , Oswald Gerda , Bastian Matthias , Sigel Helmut , Lippert Bernhard
Published: March 2007

Coordination of two monoprotonated 2′‐deoxyguanosine 5′‐monophosphate species,
H(dGMP) −, via N7 to cis‐ gives the complex cis‐Pt(H · dGMP) 2 which is a four‐protonic
acid. The corresponding acidity constants were measured by potentiometric pH titrations
(25℃; I = 0.1 M, NaNO3). The first two protons are released from the two ‐P(O) 2(OH) − groups
(PKa/1 = 5.57; PKa/2 = 6.29) and the next two protons are from the H(N1) sites of the guanine
residues (PKa/3 = 8.73; PKa/4 = 9.48). The micro acidity constants of the various sites are also
evaluated. Comparison of these data with those determined for the three‐protonic H2(dGMP) ±
(PKa/1 = 2.69 for the H+(N7) site; PKa/2 = 6.29 for ‐P(O) 2(OH) − ;PKa/3 = 9.56 for H(N1)) shows that
on average the N‐7‐coordinated Pt2+ acidifies the phosphate protons by Δ pKa = 0.36 and the
H(N1) sites by Δ pKa = 0.46. These results are further compared with those obtained previously for
cis‐, where L = 9‐ethylguanine or monoprotonated 2′‐deoxycytidine 5′‐monophosphate.
Conclusions regarding platinated DNA are also presented.
Effect of Complexes of Cobalt With Aminoacids on the Replicationof Herpes Simplex Virus Type 1 (HSV‐1)
Authors: Varadinova T. , Shishkov S. , Panteva M. , Bontchev P.
Published: March 2007

Cobalt, being essential metal, influences different physiological and enzymatic functions. As cobalt
does not accumulate in the body, Co‐compounds have relatively low toxicity. The aim of the present
study is the effect of complexes of Co(II) with aminoacids ‐ lysine, arginine, histidine and serine on
HSV‐1 replication. No effect of [O2Co(his)4].nH2O and [O2Co(arg)2].nH2O on HSV‐1 infection in vitro
was found. Both, [O2Co(lys)2].nH2O and [O2Co(ser)2].nH2O suppress the attachement of HSV‐1
particles onto target cells and the viral replication as well. Moreover, the properties of the particular
Co‐complex (charge, stability, structure) are manifestated by their virucidal effect. Thus,
[O2Co(ser)2].nH2O irreversibly inhibits the infectious activity of free HSV‐1 virions, while virucidal
effect of [O2Co(lys)2].nH2O is completely reversible after the 2h of contact.
Comparison of the Antiproliferative Activity of Two AntitumourRuthenium(III) Complexes With Their Apotransferrin andTransferrin‐Bound Forms in a Human Colon Cancer Cell Line
Authors: Kratz F. , Keppler B. K. , Hartmann M. , Messori L. , Berger M. R.
Published: March 2007

Two ruthenium(III) complexes, namely trans‐indazolium[tetrachlorobis(indazole)‐
ruthenate(III)], HInd[RuInd2Cl4] and trans‐imidazolium[tetrachlorobis(imidazole)‐
ruthenate(III)], HIm[RuIm2Cl4] exhibit high anticancer activity in an autochthonous
colorectal carcinoma model in rats. Recently, it has been shown that both complexes bind
specifically to human serum apotransferrin and the resulting adducts have been studied
through spectroscopic and chromatographic techniques with the ultimate goal of preparing
adducts with good selectivity for cancer cells due to the fact that tumour cells express high
amounts of transferrin receptors on their cell surface.

In order to investigate whether the cellular uptake of the complexes was mediated by
apotransferrin or transferrin, we compared the antiproliferative efficacy of
HInd[RuInd2Cl4] and HIm[RuIm2Cl4] with its apotransferrin‐ and transferrin‐bound form
in the human colon cancer cell line SW707 using the microculture tetrazolium test (MTT).

Our results show that especially the transferrin‐bound forms exhibit high antiproliferative
activity, which exceeds that of the free complex, indicating that this protein can act as a
carrier of the ruthenium complexes into the tumor cell.
The Hypolipidemic Activity of Boronated Nucleosides in Male Mice and Rats
Authors: Burnham Bruce S. , Sood Anup , Tomasz Jeno , Powell W. J. , Spielvogel Bernard F. , Chen S. Y. , Hall Iris H.
Published: March 2007

The boronated nucleosides with varying bases and sugar moieties were
shown to be potent hypolipidemic agents in rodents. The 3′–
aminocynaoborane dideoxythymidine derivative caused reductions in serum
cholesterol and triglyceride levels, tissue lipids, VLDL and LDL
cholesterol levels while elevating HDL cholesterol levels in rodents.
The agents suppressed rat hepatic acetyl CoA synthetase, HMG‐CoA
reductase, acyl‐CoA cholesterol acyl transferase, phosphatidylate
phosphohydrolase and lipoprotein lipase activities while elevating
cholesterol‐7α‐hydroxylase activity from 25 to 100 μM.
Properties of Binuclear Rhodium(II) Complexes and TheirAntibacterial Activity
Authors: Pruchnik Florian P. , Bień Małgorzata , Lachowicz Tadeusz
Published: March 2007

Binuclear rhodium(II) complexes [Rh2Cl2(μ‐OOCR)2(N‐N)2], (RCOO) 2
and [Rh2Cl2(μ‐OOCCH3)(terpy)2](H3O)Cl2.9H2O (R = H, Me, Bun,ph, PhCHOH; N‐N = 2,2′‐bipyridine
(bpy), 1,10‐phenanthroline (phen), 2,9‐dimethyl‐1,10‐phenanthroline (dmp) and 6,7‐dimethyl‐2,3‐
di(2‐pyridyl)quinoxaline (dmpq); terpy 2,2′:6′,2′′‐terpyridine) have been synthesized and their
structure and properties have been studied by electronic, IR and  1H NMR spectroscopy.
Antibacterial activity of these complexes against Staphylococcus aureus and Escherichia coli has
been investigated. The most active antibacterial agents against S. aureus were
, ,
and which were considerably more active than the appropriate
nitrogen ligands. The complexes show rather low activity against E. coli.
Pharmacological Role of Anions (Sulphate, Nitrate, Oxalate andAcetate) on the Antibacterial Activity of Cobalt(II), Copper(II)and Nickel(II) Complexes With Nicotinoylhydrazine‐Derived ONO,NNO and SNO Ligands
Authors: Chohan Zahid Hussain , Rauf Abdur
Published: March 2007

Mixed ligands biologically active complexes of cobalt(II), copper(II) and nickel(II) with
nicotinoylhydrazine‐derived ONO, NNO and SNO donor schiff‐base ligands having the
same metal ion but different anions such as sulphate, nitrate, oxalate and acetate have been
synthesised and characterised on the basis of their physical, analytical and spectral data. In
order to evaluate the role of anions on their bioability, these ligands and their synthesised
metal complexes with various anions have been screened against bacterial species such as
Escherichia coli, Pseudomonas aeruginosa and Staphylococcus aureus and the title studies have proved a definative role of anions in increasing the biological activity
The Pharmacological Activities of the Metabolites ofN‐[(Trimethylamineboryl)‐Carbonyl]‐L‐Phenylalanine Methyl Ester
Authors: Miller M. C. , Sood A. , Spielvogel B. F. , Shrewsbury R. P. , Hall I. H.
Published: March 2007

The metabolites of N‐[(trimethylamineboryl)‐carbonyl]‐L‐phenylalanine methyl ester 1
proved to be active in a number of pharmacological screens where the parent had previously demonstrated potent activity. The proposed metabolites demonstrated significant activity as
cytotoxic, hypolipidemic, and anti‐inflammatory agents. In cytotoxicity screens several of the
proposed metabolites afforded better activity than the parent compound against the growth of
suspended and solid tumor cell lines. Evaluation of in vivo hypolipidemic activity demonstrated
that the proposed metabolites of 1 were only moderately active and were generally less effective
than the parent compound. Interestingly, L‐phenylalanine methyl ester hydrochloride 3, which
contains no boron atom, demonstrated equivalent hypolipidemic activity as the parent at 8
mg/kg/day in CF1 male mice. As anti‐inflammatory agents the proposed metabolites
demonstrated variable capacities to reduce foot pad inflammation. These compounds were
similarly effective as the parent 1 at blocking local pain and were generally better than the parent
at protecting CF1 male mice from LPS induced sepsis.
Synthesis, Characterization and Solution Chemistry oftrans‐Indazoliumtetrachlorobis(Indazole)Ruthenate(III), a NewAnticancer Ruthenium Complex. IR, UV, NMR, HPLC Investigations andAntitumor Activity. Crystal Structures of trans‐1‐Methyl‐Indazoliumtetrachlorobis‐(1‐Methylindazole)Ruthenate(III)and its Hydrolysis Product trans‐Monoaquatrichlorobis‐(1‐Methylindazole)‐Ruthenate(III)
Authors: Lipponer Kari-Georg , Vogel Ellen , Keppler Bernhard K.
Published: March 2007

Besides intensive studies into the synthesis of the complex trans‐Hlnd[RuCl4(ind) 2] (Ind = indazole)
1, which differs remarkably from the usual method for the complexes of the HL[RuCl4L2] ‐ type,
competitive products and hydrolysis of this species are described. Stability and pseudo‐first‐order
rate constant under physiological conditions of complex 1 in comparison with the analogous imidazole
complex trans‐Hlm[RuCl4(im) 2] (Im = imidaZole) ICR were examined by means of HPLC, UV
and conductivity measurements (Kobs.(1) = 1.55 × 10-4s-1; Kobs.(ICR) = 9.10 × 10-4s-1). An attempt
was made to elucidate the bonding conditions in 1 by studying the reactions of Ru(lll) and the two
N‐methyl isomers of indazole. It can be expected that bonding in the unsubstituted ligand should
occur via the N2 nitrogen. The molecular structures of the complex trans‐H(1‐Melnd)[RuCl4(1 − Melnd) 2] × 1H2O (1‐Melnd = 1‐methylindazole) 6 and its hydrolysis product in aqueous solution
[RuCl3(H2O)(1‐Melnd)2]7 were determined crystallographically. After anisotropic refinement of F
values by least squares, R is 0.053 for 6 and 0.059 for 7. Both complexes crystallize with four molecules in a unit cell of monoclinic symmetry. The space group is P2.1/n for 6 with cell dimensions
a = 10.511Å, b = 13.87Å, c = 19.93Å, and β = 98.17° and C2/c for 7 with a = 19.90Å, b = 10.94Å, c = 8.490Å and β = 96.74° The fact that the aqua species 7 could be isolated after dissolving
6 in a water/acetone solution confirmed the theory of many Ru(lll) complexes being initially
transformed, under physiological conditions, into aqua complexes in a first and often rate‐determining
hydrolysis step. Compounds 1 and ICR are potent antitumor agents which exhibit activity
against a variety of tumor cells and experimental tumor models in animals, including autochthonous
colorectal tumors. Clinical studies with 1 are in preparation.
Transepithelial Transport and Metabolism of Boronated DipeptidesAcross Caco‐2 and HCT‐8 Cell Monolayers
Authors: Elkins Amy L. , Eley John G. , Miller Merrill C. , Hall Iris H. , Sood Anup , Spielvogel Bernard
Published: March 2007

Oral delivery of proteins and peptides as therapeutic agents is problematic due to their low bioavailability.
This study examined the effect of boronation on the transepithelial transport and metabolism of three
glycine‐phenylalanine dipeptides in Caco‐2 and HCT‐8 cell monolayers. The three dipeptides exhibited
passive transport characteristics in the monolayer systems. However, metabolism of the boronated
dipeptides did occur, but to a lesser extent than the non‐boronated glycine‐phenylalanine dipeptide. The
same metabolic scheme was seen in both cell monolayer system, but greater metabolism was seen in the
HCT‐8 cell monolayers.