Indian Journal of Chemistry

Sect. A: Inorganic, Bio-inorganic, Physical, Theoretical & Analytical

CODEN: ICACEC; ISSN: 0376-4710 (Print), 0975-0975 (Online)

 

http://www.niscair.res.in;http://nopr.niscair.res.in

Total visitors: 9982 since 18-03-2011

 

Special Issue on Bioinorganic Chemistry

VOLUME 50A

NUMBER 3-4

March-April 2011


Cover Page

Foreword

Preface

CONTENTS

Advances in Contemporary Research

 

355

 

Substrate orientation and the origin of catalytic power in xanthine oxidoreductase

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Hongnan Cao, James Pauff & Russ Hille*

 

 

 

 

Recent efforts towards understanding the role of active site amino acid residues in accelerating reaction rate have been reviewed.

 

 

 

 

363

 

Probing dioxygen activation mechanisms in
heme-containing enzymes
by heme models

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Jin-Gang Liu & Yoshinori Naruta*

 

 

 

 

Recent synthetic model studies on the mechanism of dioxygen reduction reaction involved in cytochrome c oxidase as well as on the dioxygen binding and activation associated with general heme-containing enzymes have been summarized.

 

 

 

 

 

374

 

Bacterial model systems for cytochrome c oxidase biogenesis

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

A Hannappel, F A Bundschuh, P Greiner,
M Alles, C Werner, O M Richter & B Ludwig*

 

 

 

 

Biogenesis of the enzyme is a complex process involving up to 30 accessory proteins in higher eukaryotes. The chaperones required during early biogenesis steps have been reviewed, with special emphasis on the bacterial counterparts.

 

 

 

 

 

 

383

 

Recent advances in metal-phenoxyl radical chemistry

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Yuichi Shimazaki* & Osamu Yamauchi*

 

 

 

 

The phenolate ligand is well-known as one of the
non-innocent ligands in inorganic and coordination chemistry. This review focuses on metal–phenolate complexes and their one-electron oxidized species and compares the properties of the metal–phenoxyl and high-valent metal–phenolate complexes.

 

 

 

 

 

 

395

 

Differences between two active forms of CO-bound soluble guanylate cyclase in the presence of activators and substrate and their populations revealed by resonance Raman spectroscopy

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Biswajit Pal & Teizo Kitagawa*

 

 

 

 

Effects of exogenous compounds, YC-1 and BAY 41-2272, on CO-bound soluble guanylate cyclase are discussed. Structural changes of heme, including the vinyl and propionate side chains, upon binding of YC-1/BAY 41-2272 play an important role in the activation of this enzyme.

 

Papers

 

401

 

Hydrosulfido molybdenum(V) complexes in relevance to xanthine oxidase

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Joyee Mitra & Sabyasachi Sarkar*

 

 

 

 

Rare hydrosulfido coordinated Mo(V) complexes are synthesized in relevance to xanthine oxidase. The dimeric form, and not the monomeric form, could be stabilized due to high reactivity.
DFT calculations show involvement of Mo and S (from SH) orbitals in HOMO.

 

 

409

 

Perchlorate reduction to chloride by the dimolybdenum(II) core: Making a case for molybdenum cofactor (MoCo) in the perchlorate reductase enzyme

 

 

 

 

 

 

 

 

 

 

 

Moumita Majumdar & Jitendra K Bera*

 

 

 

 

Ligand-transfer reaction from quadruply bonded [MoIIMoII] core to [CuI…CuI] unit proceeds with concomitant reduction of ClO4¯® Cl¯.

 

 

414

 

Moving iron in ferritin: Leucine 154, a residue near Fe(III) during mineral buildup minimizes mineral dissolution

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Suranjana Haldar, Takehiko Tosha &
Elizabeth C Theil*

 

 

 

 

Mineral dissolution from eukaryotic ferritin protein nanocages is influenced by conserved residue leucine 154. The residue (illustrated in red) is identified by proximity to ferric oxo mineral nuclei by NMR; view from the inside of the ferritin protein cage (yellow polypeptide helices). Each L154 residue is at the entry to the mineralization cavity, ~ 60 % of the protein cage volume, from each of the 24-subunit  nucleation channels, and, because of cage geometry, in a group of four L154 residues around the four-fold axes of the cage

 

 

 

420

 

Iron(II)-catecholate complexes of a monoanionic facial N3 ligand: Structural and functional models of the extradiol cleaving catechol dioxygenases

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Sayantan Paria, Partha Halder,
Biswarup Chakraborty & Tapan Kanti Paine*

 

 

 

 

The iron(II)-3,5-di-tert-butylcatecholate complex of
hydrotris(3,5-diphenylpyrazole-1-yl)borate ligand reacts with dioxygen to selectively give extradiol cleavage products of catechol.

 

 

 

427

 

Oxidation of dibenzothiophene by mononuclear non-heme iron complexes: A biomimetic approach for oxidative desulphurization

 

 

 

 

 

 

 

 

 

 

 

 

Anil Kumar Vardhaman, Subhajit Sikdar & Chivukula V Sastri*

 

 

 

 

 

 

 

432

 

Synthesis, structure and properties of a high-spin Fe(III) porphyrin with non-equivalent axial ligands: Implications for the hemoproteins

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Arvind Chaudhary, Ranjan Patra &
Sankar Prasad Rath*

 

 

 

 

Synthesis and X-ray structure of a six-coordinate (porphinato)iron(III) derivative, having mixed-axial ligation of perchlorate and dimethylformamide with no displacement of metal in a nonplanar porphyrinic environment, is reported for the first time.

 

 

 

438

 

Interaction of gammaxene with site specific mutants of cytochrome P450cam

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Saptaswa Sen, Soumen Kanti Manna &
Shyamalava Mazumdar*

 

 

 

 

Site-specific mutation studies of cytochrome P450cam show that Y96F, Y96F/L244A and Y96F/T101V mutants of the enzyme bind and metabolize the halogenated pesticide, gammaxene, making them potential green biocatalysts for environmental applications.

 

 

 

447

 

Effect of b-lactamase-catalyzed hydrolysis of cephalosporins on peroxynitrite-mediated nitration of serum albumin and cytochrome c

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Surendar Reddy Jakka & Govindasamy Mugesh*

 

 

 

 

Some cephalosporin-based antibiotics effectively inhibit peroxynitrite-mediated protein tyrosine nitration upon hydrolysis by β-lactamase. The inhibition is mainly due to the elimination of heterocyclic thiol/thione moieties from cephalosporins by the
β-lactamase-mediated hydrolysis.

 

 

 

453

 

A phosphorus-supported coumarin-containing ligand as a fluorescence probe for detection of  Cu(II) and Ag(I) ions

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Vadapalli Chandrasekhar*, Mrituanjay D Pandey, Biswanath Das, Bani Mahanti & Tapas Senapati

 

 

 

 

A phosphorus-supported fluorescent probe, N3P3(O2C12H8)2[N(Me)N=CHR]2, (RCHO = 7-diethylamino-coumarin-3-aldehyde) has been synthesized by the condensation of gem-N3P3(O2C12H8)2[N(Me)NH2]2 with 7-diethylamino-coumarin-3-aldehyde. It is shown to be an excellent fluorescence-based chemosensor of Cu2+ and Ag+ ions in aqueous solutions.

 

 

 

459

 

Catalytic oxidation of benzene by mononuclear copper(II) complexes with a bis(imidazolyl)methane ligand

 

 

 

 

 

 

 

 

 

Mana Goto, Yuji Kajita & Hideki Masuda*

 

 

 

 

 

 

465

 

Copper(I) complexes of modified nucleobases and vitamin B3 as potential chemotherapeutic agents:
In vitro and in vivo studies

 

 

 

 

 

 

 

 

 

 

 

 

 

 

N J M Sanghamitra, M K Adwankar, A S Juvekar, V Khurajjam, C Wycliff, A G Samuelson*

 

 

 

 

Thionucleobase and nicotinamide containing copper(I) phosphine complexes with potent anticancer activities are reported.

 

 

 

 

474

 

Synthesis, structure and anticancer activity of copper(II) complexes of N-benzyl-2-(diethylamino)acetamide and
2-(diethylamino)-N-phenylethylacetamide

 

 

 

 

 

 

 

 

 

 

 

 

 

Amit P Singh, Nagendra K Kaushik,
Akhilesh K Verma & Rajeev Gupta*

 

 

 

 

Two copper(II) complexes have been synthesized with two new bidentate amide-based ligands. Anti–proliferative studies against the U87 and HeLa cancerous cells indicate promising cytotoxicity. Despite potent in vitro activity, both complexes exhibit diminished cytotoxicity against the normal human HEK cells.

 

 

 

 

484

 

Bidentate coordination of a potentially tridentate ligand. A mononuclear four-coordinate Ni(II) complex supported by two o-iminobenzosemiquinonato units

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Atasi Mukherjee & Rabindranath Mukherjee*

 

 

 

 

A potentially tridentate ligand with N,O,S donor sites coordinates to a NiII ion as a bidentate ligand, utilizing only N and O donor sites in its o-iminobenzosemiquinonate(1–) π-radical form.

 

 

 

 

491

 

Cobalt hexamine trichloride induced toroidal condensation of FtsZ

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Anuradha Kuchibhatla, Jayesh Bellare &
Dulal Panda*

 

 

 

 

 

 

498

 

Density functional theory calculations on Fe2S2 clusters: Effect of ligand environment on geometric/electronic structure and reduction potential

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Abhishek Dey

 

 

 

 

 

 

 

503

 

Density functional theory investigations of the  catalytic mechanism of β-carbonic anhydrase

 

 

 

 

 

 

 

 

 

 

 

 

 

 

V Hakkim, V Rajapandian & V Subramanian*

 

 

 

 

 

 

511

 

A comparative study of third-order optical nonlinearity of symmetrical dipolar chromogenic probes and their enhancement by different
metal ions

 

 

 

 

 

 

 

 

 

 

 

Atanu Jana, Jong Min Lim, Sun Woo Park,
Dongho Kim* & Parimal K Bharadwaj*

 

 

 

 

Three dipolar NLO-phores consisting of different conjugation lengths as well as binding sites have been synthesized to obtain symmetrical D-p-D systems. In presence of metal ions, these dipolar moieties transform into A-p-A systems showing very large two-photon absorption cross-section values.

 

 

 

 

519

 

Photocytotoxicity and DNA photocleavage activity of La(III) and Gd(III) complexes of phenanthroline bases

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Akhtar Hussain, Sounik Saha, Ritankar Majumdar, Rajan R Dighe & Akhil R Chakravarty*

 

 

 

 

The lanthanum(III) and gadolinium(III) complexes of dipyridophenazine base show significant photo-induced plasmid DNA cleavage activity  and photocytotoxicity in HeLa cancer cells in UV-A light of 365 nm. The dark toxicity of the dppz base is significantly reduced upon binding to the lanthanide(III) ions, while retaining its photocytotoxicity.

 

 

 

531

 

Chromium(III) mediated conformational changes associated with alterations in the enzymatic activity of BSA: Influence of the coordinated ligand

 

 

 

 

 

 

 

 

 

 

 

 

Natesasn Sella Raja, H Yamini Shrivastava & Balachandran Unni Nair*

 

 

 

 

The structural and functional changes brought about in BSA due to interaction with Cr(III) complexes is largely dependent on the ligand environment of the complex.

 

 

 

 

539

 

Structural basis for preferential Ca2+-displacement by a paramagnetic ion (Ce3+) in non-myristoylated neuronal calcium sensor-1

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

 

Kousik Chandra, A L Susmitha, Y Sharma &
K V R Chary*

 

 

 

 

The relative specificity of the individual Ca2+-binding sites
present in a 190 amino acid long neuronal calcium sensor protein (r = 23 kDa) has been studied at the microscopic level by
NMR by looking at the Ca2+-displacement by a paramagnetic metal ion (Ce3+).

 

 

 

 

Authors for correspondence are indicated by (*)

 

 

 

 

 

Advances in Contemporary Research

 

Indian Journal of Chemistry

Vol. 50A, March-April 2011, pp. 355-362

 

Substrate orientation and the origin of catalytic power in xanthine oxidoreductase

Hongnan Cao, James Pauff & Russ Hille*

Department of Biochemistry,The University of California, Riverside, CA  92521, USA

Email: russ.hille@ucr.edu

Received 23 July 2010; accepted 25 August 2010

With the chemical course of the reaction catalyzed by the molybdenum-containing hydroxylase xanthine oxidoreductase now relatively well-understood, efforts in the field have now turned to understanding the catalytic power of the enzyme in the context of its structure. The present minireview is an account of recent efforts, from the authors’ laboratory and elsewhere, towards understanding the role of active site amino acid residues in accelerating reaction rate.  On the basis of recent site-directed mutagenesis work, in conjunction with protein X-ray crystallography, it is now possible to attribute the specific extent to which each contributes to transition state stabilization and the means by which this occurs.

Keywords: Bioinorganic chemistry, Catalysis, Reaction mechanisms, Molybdenum enzymes, Xanthine oxidoreductase

 

Indian Journal of Chemistry

Vol. 50A, March-April 2011, pp. 363-373

 

Probing dioxygen activation mechanisms in heme-containing enzymes by heme models

Jin-Gang Liu & Yoshinori Naruta*

Institute for Materials Chemistry and Engineering, Kyushu University, Higashi-ku, Fukuoka, 812-8581, Japan

Email: naruta@ms.ifoc.kyushu-u.ac.jp

 

Received 10 August 2010; accepted 4 December 2010

In this mini-review, we summarize our recent synthetic model studies on the mechanism of dioxygen reduction reaction involved in cytochrome c oxidase (CcO), as well as on the dioxygen binding and activation associated with general heme-containing enzymes. A series of heme/copper dinuclear complexes bearing a cross-linked His-Tyr mimic have been designed and synthesized as synthetic models of the active site of CcO, focusing on the possible role(s) of the cross-linked His-Tyr-CuB moiety. The spectroscopic evidences from the oxygenation reaction of these model compounds demonstrate that the role(s) of the cross-linked His-Tyr moiety is more likely to be structural and a proton mediator rather than acting as the fourth electron donor in the dioxygen reduction process. It also implies that after one-electron reduction of the oxyheme unit in CcO under physiological conditions, O-O bond cleavage could occur through a FeIII-OOH rather than a peroxo FeIII-(O22-)-CuII species. In addition, as key intermediates involved in the catalytic cycles of heme-containing enzymes, the low-spin end-on ferric-peroxo and ferric-hydroperoxo intermediates have been successfully captured and spectroscopically characterized in solution for the first time by using of delicate designed heme models. The results suggest the crucial role of the axial imidazole ligation to heme for O2 activation

Keywords: Bioinorganic chemistry, Cytochrome c oxidase, Heme proteins, Enzyme models, Dioxygen activation

 

Indian Journal of Chemistry

Vol. 50A, March-April 2011, pp. 374-382

 

Bacterial model systems for cytochrome c oxidase biogenesis

A Hannappel, F A Bundschuh, P Greiner, M Alles, C Werner, O M Richter & B Ludwig*

Molecular Genetics, Institute of Biochemistry, Goethe University, Max-von-Laue-Strasse 9,
D-60438 Frankfurt am Main, Germany

Email: Ludwig@em.uni-frankfurt.de

Received 2 September 2010; accepted 31 October 2010

Cytochrome c oxidase is the key player in cellular respiration, catalysing the reduction of molecular oxygen to water via its internal heme and copper redox centres. Biogenesis of the enzyme is a complex process involving up to 30 accessory proteins in higher eukaryotes. Factors directly involved in cofactor recruitment and insertion into the two core structural subunits I and II are also present in many bacteria and have been conserved during evolution. Herein we briefly review the chaperones required during early biogenesis steps, with special emphasis on the bacterial counterparts.

Keywords:   Bioinorganic chemistry, Biogenesis, Oxidase assembly, Terminal oxidase, Heme copper oxidase, Chaperone proteins, Heme a, Surf1, CbaX, CtaG, Cox11, Sco

 

Indian Journal of Chemistry

Vol. 50A, March-April 2011, pp. 383-394

 

Recent advances in metal-phenoxyl radical chemistry

Yuichi Shimazakia, * & Osamu Yamauchib, *

aCollege of Science, Ibaraki University, Mito 310-8512, Japan

Email: yshima@mx.ibaraki.ac.jp

bFaculty of Chemistry, Materials, and Bioengineering, Kansai University, Suita, Osaka 564-8680, Japan

Email: oyamauchi36bioin@wonder.ocn.ne.jp

Received 19 August 2010; accepted 16 December 2010

The phenolate ligand is well-known as one of the non-innocent ligands. It is typically shown in biological systems as the ligand of a single copper enzyme galactose oxidase, forming a relatively stable Cu(II)-phenoxyl radical intermediate. On the other hand, some of the one-electron oxidized metal-phenolate complexes are revealed to be high valent metal-phenolate complexes, which are isoelectronic with the metal-phenoxyl radical complexes. Therefore, characterization of the one-electron oxidized metal-phenolate complexes has recently been the subject of intense studies aiming at understanding their oxidation states under the given conditions. This review focuses on metal-phenolate complexes and their one-electron oxidized species and compares the properties of the metal-phenoxyl and high-valent metal-phenolate complexes.

Keywords: Bioinorganic chemistry, Metal-phenoxyl radicals, Phenoxyl radicals, Non-innocent ligands

 

Indian Journal of Chemistry

Vol. 50A, March-April 2011, pp. 395-400

 

Differences between two active forms of CO-bound soluble guanylate cyclase in the presence of activators and substrate and their populations revealed by resonance Raman spectroscopy

Biswajit Pala & Teizo Kitagawab, *

aCentre for Cellular and Molecular Biology, Uppal Road, Hyderabad 500 007, India

bPicobiology Institute, Graduate School of Life Science, University of Hyogo, 3-2-1 Koto, Kamigori,
Ako-gun, Hyogo, 678-1297 Japan

Email : teizo@sci.u-hyogo.ac.jp

Received 31 October 2010; accepted 12 December 2010

Soluble guanylate cyclase is a dimeric (ab) enzyme catalyzing the conversion of GTP to cyclic GMP which acts as a second messenger in cellular signaling. It is the only known physiological receptor of NO and binding of NO to its heme, which is covalently bound via a conserved His-b105, activates this enzyme several hundred folds over its basal level. It is known that NO-binding causes the cleavage of
Fe-His bond. CO marginally activates sGC, and in the presence of some activator molecules like YC-1 and BAY it activates to the same level as NO-bound sGC, although a mechanism of this synergistic effect is hardly understood. Herein, we present evidences for the presence of two forms of CO-bound sGC in the presence of activators and deduce their structural differences and population on the basis of resonance Raman spectroscopy. A mechanism for the synergetic effect has been discussed.

Keywords: Bioinorganic chemistry, Soluble guanylate cyclase, Resonance Raman spectroscopy,
Enzyme activation

 

Papers

 

Indian Journal of Chemistry

Vol. 50A, March-April 2011, pp. 401-408

 

Hydrosulfido molybdenum(V) complexes in relevance to xanthine oxidase

Joyee Mitra & Sabyasachi Sarkar*

Department of Chemistry, Indian Institute of Technology Kanpur, Kanpur 208 016, India

Email: abya@iitk.ac.in

Received 10 November 2010, accepted 20 January 2011

The rare and extremely unstable M-SH linkage uniquely prevalent in xanthine oxidase class of enzymes, has been modeled with the relevant Mo(V)-SH moiety in three new complexes. These complexes are characterized fully by X-ray structure analysis, spectroscopic studies and by DFT level of calculations.

Keywords: Bioinorganic chemistry, Molybdoenzymes, Molybdenum, Xanthine oxidase, Hydrosulfides, Density functional calculations

 

Indian Journal of Chemistry

Vol. 50A, March-April 2011, pp. 409-413

 

Perchlorate reduction to chloride by the dimolybdenum(II) core: Making a case for molybdenum cofactor in the perchlorate reductase enzyme

Moumita Majumdar & Jitendra K Bera*

Department of Chemistry, Indian Institute of Technology Kanpur, Kanpur 208 016, India

Email: jbera@iitk.ac.in

Received 10 November 2010; accepted 11 January 2011

Ligand-transfer reaction from the quadruply bonded complex cis-[Mo2(pzNP)2(OAc)2][BF4]2 (1) (pzNP = 2-(2-pyrazinyl)-1,8-naphthyridine) to non-bonded dicopper(I) core proceeds with the concomitant oxidation of the [Mo2]4+ core by the perchlorate anion, resulting in the [Cu2(µ-Cl)(pzNP)2][ClO4] (2) and oxo-molybdenum species. X-ray analysis of (2) shows the presence of a chloride anion bridging the two Cu(I) atoms. The chloride originates from the quantitative reduction of one perchlorate anion by the electron-rich dimolybdenum(II) species, mimicking the functional role of molybolenum cofactor in the perchlorate reducing bacteria.

Keywords:  Bioinorganic chemistry, Perchlorate reduction, Ligand transfer reactions, Molybdenum cofactor, Dimolybdenum, Oxomolybdenum, Copper

 

Indian Journal of Chemistry

Vol. 50A, March-April 2011, pp. 414-419

 

Moving iron in ferritin: Leucine 154, a residue near Fe(III) during mineral buildup minimizes mineral dissolution

Suranjana Haldara, Takehiko Toshab, † & Elizabeth C Theila, b, *

aCouncil on Bioiron at Children’s Hospital Oakland Research Institute, 5700 Martin Luther King Jr. Way,
Oakland, CA 94609, USA

bDepartment of Nutritional Science and Toxicology, University of California, Berkeley, CA 94720, USA

Email: etheil@chori.org

Received 16 October 2010; accepted 27 October 2010

Ferritins, ancient protein nanocages, reversibly synthesize hydrated ferric oxide concentrates; minerals with thousands of iron atoms grow in 8 nm cavities of the 12 nm cages of plant and animal ferritins. Cells use ferritin iron for iron-protein cofactor synthesis and as a trap for reactive iron from damaged iron-proteins. Recent ferritin structural studies show the iron entry path through iron ion channels, oxidoreductase sites and nucleation channels, a distance of ~ 5 nm from one end of the cage subunits
(4 α-helix bundles) to the other. We now show that conserved L154, at the cavity entrance in a loop between helix 4 and a fifth short helix, slows mineral dissolution (50% mineral dissolution was >7 times faster in L154G ferritin). The effects on iron exit of leucine/glycine replacement in residue 154 at the end of iron entry path shows convergence of the iron entry and exit at L154 on the cage edge. The L154-dependent cage stabilization mechanism and the path that Fe(II) follows from the mineral surface to the ferritin protein are problems that remain unsolved in understanding the complex, eukaryotic ferritin protein cages that evolved for natural iron metabolism and are also used for imaging, nanocatalysis and nanomaterials.

Keywords: Bioinorganic chemistry, Catalysis, Protein cages, Ferritin, Mineral dissolution, Iron, Biominerals

 

Indian Journal of Chemistry

Vol. 50A, March-April 2011, pp. 420-426

 

Iron(II)-catecholate complexes of a monoanionic facial N3 ligand: Structural and functional models of the extradiol cleaving catechol dioxygenases

Sayantan Paria, Partha Halder, Biswarup Chakraborty & Tapan Kanti Paine*

Department of Inorganic Chemistry, Indian Association for the Cultivation of Science,
2A&2B Raja S C Mullick Road, Jadavpur, Kolkata 700 032, India

 

Email: ictkp@iacs.res.in

Received 5 November 2010; accepted 5 January 2011

Two biomimetic iron(II)-catecholate complexes, [(TpPh2)FeII(CatH)] (1) and [(TpPh2)FeII(DBCH)] (2) (where TpPh2 = hydrotris(3,5-diphenylpyrazole-1-yl)borate, CatH = monoanionic pyrocatecholate and DBCH = monoanionic 3,5-di-tert-butyl catecholate), have been isolated and characterized to study their reactivity towards dioxygen. The single-crystal X-ray structure of (1) reveals a high-spin iron(II) center ligated by the monoanionic facial N3 ligand and a monoanionic catecholate, giving rise to a trigonal bipyramidal coordination geometry. Complex (1) represents the first structurally characterized five-coordinate iron(II)-catecholate complex with an asymmetric bidentate binding motif of monoanionic catecholate. While (1) reacts with dioxygen to form the corresponding iron(III)-catecholate, (2) reacts with dioxygen to give 75 % extradiol and 25 % intradiol cleavage products via an iron(III)-catecholate intermediate species. Complex (2) is a potential functional model of extradiol cleaving catechol dioxygenases.

Keywords: Bioinorganic chemistry, Iron, Oxidative cleavage, Catechol

Indian Journal of Chemistry

Vol. 50A, March-April 2011, pp. 427-431

 

Oxidation of dibenzothiophene by mononuclear non-heme iron complexes: A biomimetic approach for oxidative desulphurization

Anil Kumar Vardhaman, Subhajit Sikdar & Chivukula V Sastri*

Department of Chemistry, Indian Institute of Technology Guwahati, Assam, India

sastricv@iitg.ernet.in

Received 29 January 2011; accepted 9 February 2011

Dibenzothiophene (DBT), a common component of crude oil, is a widespread environmental pollutant with known adverse effects. Oxidation of DBT to dibenzothiophene sulfone has been examined using
in situ generated high-valent oxo-iron(IV) complexes. The reactivities and the corresponding thermodynamic parameters are evaluated and compared with those for simple S-oxidation (thioanisole) reactions. Among the catalysts examined, [FeII(Bn-Tpen)]2+ is found to be a more efficient oxidant over [FeII(N4Py)]2+. The order of the reactivity and the evaluated thermodynamic parameters signify the role of the electron delocalization due to benzene rings for DBT oxidation.

Keywords: Bioinorganic chemistry, Oxidation, Desulphurization, Oxidative desulphurization, Iron, Dibenzothiophene

 

Indian Journal of Chemistry

Vol. 50A, March-April 2011, pp. 432-437

 

Synthesis, structure and properties of a high-spin Fe(III) porphyrin with
non-equivalent axial ligands: Implications for the hemoproteins

Arvind Chaudhary, Ranjan Patra & Sankar Prasad Rath*

Department of Chemistry, Indian Institute of Technology Kanpur, Kanpur 208 016, India

Email: sprath@iitk.ac.in

Received 5 November 2010; accepted 5 January 2011

The synthesis and X-ray structure of a six-coordinate (porphinato)iron(III) derivative having the mixed-axial ligation of perchlorate and dimethylformamide with no displacement of metal in a nonplanar porphyrinic environment is reported for the first time. The Fe-Np (Np: porphinato nitrogen) distances which range from 2.044(2) to 2.070(2) Å, leaves little doubt that the Fe(III) ion is in high-spin state which is also supported by its characteristic axial EPR spectrum at low temperature. The axial Fe-O(DMF) distance is 2.050(2) Å which is ~0.6 Å shorter than the Fe-OClO3 distance of the complex. In the complex, iron sits in the plane of four porphyrinic nitrogens even when metal coordinates to two non-equivalent axial ligands. The present study suggests that the displacement of iron in proteins is the consequence of non-equivalent axial coordination as well as the protein induced deformations at heme.

Keywords: Bioinorganic chemistry, Hemoproteins, Iron, High spin iron, Porphyrins, Mixed axial ligands

 

Indian Journal of Chemistry

Vol. 50A, March-April 2011, pp. 438-446

 

Interaction of gammaxene with site specific mutants of cytochrome P450cam

 

Saptaswa Sen, Soumen Kanti Manna & Shyamalava Mazumdar*

Department of Chemical Sciences, Tata Institute of Fundamental Research,
Homi Bhabha Road, Colaba, Mumbai 400 005, India

Email: shyamal@tifr.res.in

Received 1 November 2010; accepted 18 December 2010

Cytochrome P450cam (CYP101) from soil bacteria Pseudomonas putida, is one of the most well studied heme-b monoxygenase. A large number of X-ray crystal structures of this enzyme and its mutants are now available with different types of substrates that can be used to study the topology of the active site of the enzyme. We have a continuing interest in applying the current knowledge of cytochrome
P450cam-substrate recognition to rationally design the enzyme for the biotransformation of unnatural substrates, like gammaxene, with the long-term aim of applications in bioremediation of environmental contaminants. Comparison of the structure of target substrate with that of camphor, the natural substrate, led us to engineer the heme active-site and we have found that binding affinities significantly are increased for Y96F, Y96F/L244A and Y96F/T101V mutants. This has shown the way to new functions of the enzymes, which not only has provided a novel approach to the study of the mechanism of this complex super-family of enzymes, but has also led to the discovery of green biocatalysts for environmental applications.

Keywords:   Bioinorganic chemistry, Gammaxene, Cytochrome P450cam, Heme, Oxygenase,
Site specific mutagenesis

 

Indian Journal of Chemistry

Vol. 50A, March-April 2011, pp. 447-452

 

Effect of b-lactamase-catalyzed hydrolysis of cephalosporins on peroxynitrite-mediated nitration of serum albumin and cytochrome c

Surendar Reddy Jakka & Govindasamy Mugesh*

Department of Inorganic and Physical Chemistry, Indian Institute of Science, Bangalore 560 012, India

Email: mugesh@ipc.iisc.ernet.in

Received 28 November 2010; accepted 12 January 2011

The hydrolysis of b-lactam antibiotics by b-lactamases is one of the major bacterial defense systems. These enzymes generally hydrolyze a variety of antibiotics including the latest generation of cephalosporins, cephamycins and imipenem. In this paper, the effect of cephalosporins-based antibiotics on the peroxynitrite-mediated nitration of protein tyrosine is described. Although some of the antibiotics have weak inhibitory effect on the nitration reactions in the absence of b-lactamase, they exhibit very strong inhibition in the presence of b-lactamase. This is due to the elimination of heterocyclic thiol/thione moieties from cephalosporins by b-lactamase-mediated hydrolysis. After the elimination, the thiols/thiones effectively scavenge peroxynitrite, leading to the inhibition of the nitration reactions.

Keywords: Bioinorganic chemistry, Hydrolysis, Enzyme hydrolysis, Nitration, Protein nitration, Cephalosporins, Tyrosine, Lactams

Indian Journal of Chemistry

Vol. 50A, March-April 2011, pp. 453-458

 

A phosphorus-supported coumarin-containing ligand as a fluorescence probe for detection of Cu(II) and Ag(I) ions

Vadapalli Chandrasekhar*, Mrituanjay D Pandey, Biswanath Das, Bani Mahanti & Tapas Senapati

Department of Chemistry, Indian Institute of Technology Kanpur, Kanpur 208 016, India

Email: vc@iitk.ac.in

Received 22 November 2010; accepted 7 January 2011

A phosphorus-supported fluorescent probe N3P3(O2C12H8)2[N(Me)N=CHR]2 (RCHO = 7-diethylamino-coumarin-3-aldehyde) has been synthesized by the condensation of gem-N3P3(O2C12H8)2[N(Me)NH2]2 with 7-diethylamino-coumarin-3-aldehyde. This compound has been shown to be an excellent fluorescence-based chemosensor of Cu2+ and Ag+ ions in aqueous solution.

Keywords: Fluorescence, Chemosensors, Probes, Phosphorus ligands, Cyclophosphazene, Hydrazides,
Copper, Silver

 

Indian Journal of Chemistry

Vol. 50A, March-April 2011, pp. 459-464

 

Catalytic oxidation of benzene by mononuclear copper(II) complexes with a bis(imidazolyl)methane ligand

Mana Goto, Yuji Kajita & Hideki Masuda*

Department of Frontier Materials, Nagoya Institute of Technology, Gokiso-cho, Showa-ku,
Nagoya 466-8555, Japan

Email: masuda.hideki@nitech.ac.jp

Received 19 August 2010; accepted 28 October 2010

Catalytic oxidation of benzene under mild conditions is one of the most challenging reactions in synthetic chemistry. In order to develop a hydroxylation catalyst for benzene, we have designed and synthesized new copper(II) complexes with the bidentate ligand bis(1,4,5-trimethyl-2-imidazolyl)methane (Me6bim), [Cu(Me6bim)X2] (X = Cl, Br). This ligand provides a reaction space which can be easily accessed by exogenous substrates and has an imidazole group, which is a typical ligand of metalloenzymes. These complexes exhibit catalytic oxidation of benzene in the presence of excess H2O2 at room temperature in aqueous MeCN solution to yield phenol and 1,4-benzoquinone.

Keywords: Bioinorganic chemistry, Metalloenzymes, Catalysts, Oxidation, Benzene oxidation, Mononuclear copper, Copper, Bis(benzimidazolyl)methane

Indian Journal of Chemistry

Vol. 50A, March-April 2011, pp. 465-473

 

Copper(I) complexes of modified nucleobases and vitamin B3 as potential chemotherapeutic agents: In vitro and in vivo studies

N J M Sanghamitraa, M K Adwankarb, A S Juvekarb, V Khurajjamb & C Wycliff a, A G Samuelsona

aDepartment of Inorganic and Physical Chemistry, Indian Institute of Science, Bangalore 560 012, India

Email: ashoka@ipc.iisc.ernet.in

bDivision of Chemotherapy, Advanced Centre for Treatment, Research and Education in
Cancer (ACTREC), Tata Memorial Centre, Navi Mumbai 410 208, India

Received 27 October 2010; accepted 3 January 2011

Three new complexes of Cu(I) have been synthesized using ancillary ligands like thiopyrimidine (tp) a modified nucleobase, and nicotinamide (nic) or vitamin B3, and characterized by spectroscopy and X-ray crystallography. In vitro cytotoxicity studies of the complexes on various human cancer cell lines such as Colo295, H226, HOP62, K562, MCF7 and T24 show that [Cu(PPh3)2(tp)Cl] (1) and [Cu(PPh3)2(tp)]ClO4 (2) have in vitro cytotoxicity comparable to cisplatin. Complex [Cu(nic)3PPh3]ClO4 (3) is non-toxic and increases the life span by about 55 % in spontaneous breast tumor model. DNA binding and cleavage studies show that complex (3) binds to calf thymus DNA with an apparent binding constant of 5.9 ´ 105 M and completely cleaves super-coiled DNA at a concentration of 400 mM, whereas complexes (1) and (2) do not bind DNA and do not show any cleavage even at 1200 mM. Thus, complex (3) may exhibit cytotoxicity via DNA cleavage whereas the mechanism of cytotoxicity of (1) and (2) probably involves a different pathway.

Keywords:   Bioinorganic chemistry, Metallodrugs, Copper, Antitumor activity, Thiopyrimidine, Nicotinamide, Cytotoxicity, Lipophilicity

 

Indian Journal of Chemistry

Vol. 50A, March-April 2011, pp. 474-483

 

Synthesis, structure and anticancer activity of copper(II) complexes of N-benzyl-2-(diethylamino)acetamide and 2-(diethylamino)-
N-phenylethylacetamide

Amit P Singha, Nagendra K Kaushikb, Akhilesh K Vermaa & Rajeev Guptaa, *

aDepartment of Chemistry, University of Delhi, Delhi 110 007, India

Email: rgupta@chemistry.du.ac.in

bDr B R Ambedkar Centre for Biomedical Research, University of Delhi, Delhi 110 007, India

Received 30 October 2010; accepted 23 December 2011

The ligands N-benzyl-2-(diethylamino)acetamide, (HL1) and 2-(diethylamino)-N-phenylethylacetamide (HL2), have been used to synthesize copper(II) complexes, [Cu(HL1)2](ClO4)2 (1) and [Cu(HL2)2](ClO4)2 (2), respectively. Both complexes are well characterized by various spectral and physical methods. The crystal structure of complex (1) reveals that two bidentate ligands coordinate the Cu(II) ion via Oamide and Namine atoms in the basal plane whereas one of the ClO4- ions occupies the apical position maintaining a square–pyramidal geometry. Screening results for anti–proliferative studies against the U87 and HeLa cancerous cells indicate promising activity. The complexes enhanced growth inhibition and cell death in a concentration and time dependent manner for both U87 and HeLa cell lines. Of the two compounds, complex (2) exhibits better activity against both HeLa and U87 cells. Further, both complexes are specifically potent against U87 after 72 h of treatment. Micronucleus and apoptosis frequencies are 3 – 4 times higher in treated cells when compared with untreated control. Despite potent in vitro activity, both complexes exhibit diminished cytotoxicity against the normal human HEK cells at all effective concentrations.

Keywords: Bioinorganic chemistry, Copper, Amide-based ligands, Anti-cancer activity, Cytotoxicity

 

Indian Journal of Chemistry

Vol. 50A, March-April 2011, pp. 484-490

 

Bidentate coordination behaviour of a potentially tridentate ligand. A mononuclear four-coordinate Ni(II) complex supported by
two o-iminobenzosemiquinonato units

Atasi Mukherjee & Rabindranath Mukherjee*

Department of Chemistry, Indian Institute of Technology Kanpur, Kanpur 208 016, India

Email: rnm@iitk.ac.in

Received 23 December 2010; accepted 29 December 2010

Using a new N,O,S–potentially tridentate ligand (H2L), a mononuclear NiII complex of composition  (1) has been synthesized. The structure of the complex has been elucidated in the solution state using 1H NMR spectroscopy and in the solid state by X-ray crystallography. X-ray studies reveal that the NiII is surrounded by two o-iminobenzosemiquinonate(1–) π-radical ligands, providing a NiIIN2O2 square planar coordination environment. Notably, the thioether unit in each ligand remains non-coordinated. Cyclic voltammetric measurements of (1) show two one-electron reductive and two one-electron oxidative redox responses, which are ligand-centred in origin. Characterization of electrochemically-generated reduced and oxidized species has also been accomplished.

Keywords: Bioinorganic chemistry, Metal coordinated radicals, Non-innocent ligands, Crystal structures, Nickel

 

Indian Journal of Chemistry

Vol. 50A, March-April 2011, pp. 491-497

 

Cobalt hexamine trichloride induced toroidal condensation of FtsZ

Anuradha Kuchibhatlaa, Jayesh Bellareb & Dulal Pandaa, *

aDepartment of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Powai, Mumbai 400 076, India

bDepartment of Chemical Engineering, Indian Institute of Technology Bombay, Powai, Mumbai 400 076, India

Email: panda@iitb.ac.in

Received 1 January 2011; accepted 25 January 2011

The bacterial cell division protein, FtsZ, polymerizes to form a cytokinetic Z-ring at the midcell, which engineers bacterial cell division. Herein, we have examined the effects of an inorganic polyamine, cobalt hexamine trichloride, on the assembly of FtsZ in vitro. Cobalt hexamine trichloride strongly enhances FtsZ assembly, suppresses its GTPase activity and stabilizes FtsZ polymers. However, CoCl2 and MnCl2 have no detectable effect on the assembly of FtsZ in vitro. Interestingly, FtsZ is found to assemble into toroidal structures in the presence of low concentrations of cobalt hexamine trichloride. The Z-ring in bacterial cells appears to be a toroidal-like structure, suggesting that the use of cobalt hexamine trichloride may help to understand the assembly of FtsZ into toroidal structure. The toroidal structures may also serve as templates to build toroidal resonators for electrical and thermal applications.

Keywords: Bioinorganic chemistry, Toroidal condensation, Polymer assembly, Morphology, Polyamines, Inorganic polyamines, Cobalt hexamine trichloride, FtsZ, Z-ring

 

Indian Journal of Chemistry

Vol. 50A, March-April 2011, pp. 498-502

 

Density functional theory calculations on Fe2S2 clusters: Effect of ligand environment on geometric/electronic structure and reduction potential

Abhishek Dey

Department of Inorganic Chemistry, Indian Association for the Cultivation of Science,
Jadavpur, Kolkata 700 032, India

Email: icad@iacs.res.in

Received 14 December 2010; accepted 10 January 2011

The Fe2S2 clusters in nature are generally coordinated to the peptide backbone using thiolate ligands (from cysteines). A known variation of these are the imidazole (from histidine) coordinated active sites of Riesky proteins. Recently, a few newer modifications have been observed, e.g., the arginine coordinated cluster in biotin synthases. Very recently, a cysteine persulfide coordinated cluster has been observed in the hydrogenase maturase enzyme, HydE. Herein, density functional theory calculations are used to investigate the effect of the unusual arginine and cysteine persulfide coordinations on the geometric and electronic properties of these clusters. Further, the effect of these ligands in tuning the thermodynamic reduction potentials of these clusters has also been investigated.

Keywords: Bioinorganic chemistry, Theoretical chemistry, Density functional calculations, Iron, Sulfur clusters, Electronic structures, Reduction potentials

 

Indian Journal of Chemistry

Vol. 50A, March-April 2011, pp. 503-510

 

Density functional theory investigations of the catalytic mechanism of
β-carbonic anhydrase

V Hakkim, V Rajapandian & V Subramanian*

Chemical Laboratory, Central Leather Research Institute, CSIR, Adyar, Chennai 600 020, India

Email:subuchem@hotmail.com/ subbu@clri.res.in

Received 18 November 2010; accepted 1 December 2010

Carbonic anhydrase (CA) is an enzyme that catalyses the reversible hydration of carbon dioxide. There are three broad classes α, β, and γ, of CA, divided into three genetically unrelated families, namely, animal, plant, and bacterial Cas, respectively. The active site of this enzyme contains a zinc atom which is necessary for catalysis. In this study, the catalytic mechanism of β-CA has been investigated using its active site model employing DFT based Becke’s three parameter exchange and B3LYP method. It is evident from the results that the activation barrier for the nucleophilic attack is negligible, which is similar to that of α-CA. Furthermore, results show that Asp162-Arg164 dyad and Glu151 residues play a decisive role in the catalysis. Primarily, the catalytic dyad orients the hydroxyl group appropriately to enable nucleophilic attack and stabilizes the negative charge on the bicarbonate.

Keywords: Bioinorganic chemistry, Theoretical chemistry, Catalysis, Reaction mechanisms, Metalloenzymes, Carbonic anhydrase

Indian Journal of Chemistry

Vol. 50A, March-April 2011, pp. 511-518

 

A comparative study of third-order optical nonlinearity of symmetrical dipolar chromogenic probes and their enhancement by different metal ions

Atanu Janaa, Jong Min Limb, Sun Woo Parkb, Dongho Kimb, * & Parimal K Bharadwaja, *

aDepartment of Chemistry, Indian Institute of Technology Kanpur, 208 016, India

Email: pkb@iitk.ac.in

bSpectroscopy Laboratory for Functional π-Electronic Systems and Department of Chemistry,
Yonsei University, Seoul 120-749, Republic of Korea

Received 3 December 2010; accepted 9 January 2011

We have investigated the two-photon absorption properties of three symmetrical NLO-phores, L1, L2 and L3, having different conjugation lengths as well as different binding sites like cryptand, crown ether and bipyridyl moiety. The TPA properties have been measured by a femtosecond laser at 800 nm, which is in the window of ‘in vivo’ imaging. Upon metal ion binding, the TPA cross-section values are enhanced to different extents depending on the nature of metal ion and the overall architecture of the molecular system as well. The unique CT transition process after metal ion incorporation, along with various conjugation lengths of the NLO-phores, fully elucidates the structure-property relationship of the photophysical properties.

Keywords: Bioinorganic chemistry, Coordination chemistry, Optical nonlinearity, NLO-phores,
Two photon absorption, Chromogenic probes

 

Indian Journal of Chemistry

Vol. 50A, March-April 2011, pp. 519-530

 

Photocytotoxicity and DNA photocleavage activity of La(III) and
Gd(III) complexes of phenanthroline bases

 

Akhtar Hussaina, Sounik Sahaa, Ritankar Majumdarb, Rajan R Digheb & Akhil R Chakravarty a, *

aDepartment of Inorganic and Physical Chemistry, Indian Institute of Science, Bangalore 560 012, India

Email: arc@ipc.iisc.ernet.in

bDepartment of Molecular Reproduction, Development and Genetics, Indian Institute of Science,
Bangalore 560 012, India

Received 1 October 2010; accepted 20 January 2011

Lanthanide(III) complexes [La(B)(acac)3] (13) and [Gd(B)(acac)3]  (46), where B is a N,N-donor phenanthroline base, viz., 1,10-phenanthroline (phen in 1, 4), dipyrido[3,2-d:2',3'-f]quinoxaline (dpq in 2, 5) and dipyrido[3,2-a:2’,3’-c]phenazine (dppz in 3, 6), have been prepared and characterized. The Gd(III) complexes 46 are structurally characterized by single crystal X-ray crystallography. The complexes display GdO6N2 coordination with the ligands showing bidentate chelating mode of bonding. The complexes are non-electrolytic in aqueous DMF and exhibit ligand-centered absorption bands in the UV region. The dppz complexes show a band at 380 nm in DMF. The La(III) complexes are diamagnetic. The Gd(III) complexes are paramagnetic with magnetic moment that corresponds to seven unpaired electrons. The complexes are avid binders to calf thymus DNA giving Kb values in the range of 4.7 ´ 104 - 6.1 ´ 105 M-1 with a relative binding order: 3, 6 (dppz) > 2, 5 (dpq) > 1, 4 (phen). The binding data suggest DNA surface and/or groove binding nature of the complexes. The dpq and dppz complexes efficiently cleave SC DNA to its nicked circular form in UV-A light of 365 nm via formation of both singlet oxygen (1O2) and hydroxyl radical (HO) species. The dppz complexes 3 and 6 exhibit significant PDT effect in HeLa cervical cancer cells giving respective IC50 value of 460(±50) and 530(±30) nM in UV-A light of 365 nm, and are essentially non-toxic in dark with an IC50 value of >100 µM. The dppz ligand alone is cytotoxic in dark and UV-A light. A significant decrease in the dark toxicity of the dppz base is observed on binding to the Ln(III) ion while retaining its photocytotoxicity.

Keywords:   Bioinorganic chemistry, Lanthanides, Phenanthroline bases, Crystal structures, DNA binding, DNA photocleavage, Photocleavage, Photocytotoxicity, Cytotoxicity

 

Indian Journal of Chemistry

Vol. 50A, March-April 2011, pp. 531-538

 

Chromium(III) mediated conformational changes associated with alterations in the enzymatic activity of BSA: Influence of the coordinated ligand

Natesasn Sella Raja, H Yamini Shrivastava & Balachandran Unni Nair*

Chemical Laboratory, Central Leather Research Institute, Adyar, Chennai 600 020, India

Email: bunair@clri.res.in

Received 4 November 2010; accepted 20 December 2010

Interaction of three chromium(III) complexes, [Cr(salen)(H2O)2]ClO4 (1), Na[Cr(EDTA)(H2O)] (2) and [Cr(en)3]Cl3 (3) with bovine serum albumin (BSA) has been investigated in order to understand the role of coordinated ligand in mediating the interaction between the protein and chromium(III) ion. Binding of (1) and (2) to BSA has been found to result in increase in the esterase activity of BSA from 2.41 to 2.72 and 2.62 U/L respectively. On the other hand, binding of (3) results in decrease of the activity from 2.41 to 1.91 U/L. These changes in the esterase activity are also reflected in the conformation of BSA in the presence of (1), (2) and (3). CD spectrum of BSA clearly indicates that binding of (1) and (2) leads to increase in the helicity of BSA, whereas binding of (3) leads to decrease in the helicity of the protein. Such a change in the helicity of BSA leads to change in the orientation of active amino acids (Tyr 411 and Arg 410) in the protein, thus affecting the esterase activity of protein. The nature of the coordinated ligand has also been found to influence the stability of BSA against trypsin digestion.

Keywords: Bioinorganic chemistry, Metalloproteins, Chromium, Tryptic digestion, Circular dichroism,
Bovine serum albumin

 

Indian Journal of Chemistry

Vol. 50A, March-April pp. 539-547

 

Structural basis for preferential Ca2+-displacement by a paramagnetic ion (Ce3+) in non-myristoylated neuronal calcium sensor-1

Kousik Chandraa, A L Susmithaa, Y Sharmab & K V R Charya, *

aDepartment of Chemical Sciences, Tata Institute of Fundamental Research, Mumbai 400 005, India

bCenter for Cellular and Molecular Biology, Hyderabad 500 007, India

Email: chary@tifr.res.in

Received 7 December 2010; accepted 29 December 2010

We have investigated the Ca2+-displacement by a trivalent lanthanide ion (Ce3+) in a Ca2+-sensor protein called neuronal calcium sensor-1 in its non-myristoylated form by NMR. We observe that all the Ca2+ bound to the three active Ca2+-binding loops are displaced by Ce3+. Microscopically, NMR paramagnetic titration data on [Ca2+]-non-myr-NCS-1 shows that the Ce3+ displaces Ca2+ first from both sites, EF2 and EF3, almost in parallel, followed by the displacement from EF4. Between EF2 and EF3, the NMR data conclusively shows that the Ca2+-displacement is more prominent in EF2 as compared to that in EF3. These findings have been attributed to: (i) the presence of a higher number of negatively charged residues in EF2 compared to EF3 and EF4, and, (ii) the presence of a Lys instead of a highly conserved Phe at –4 position in the first Ca2+-binding loop, which results in a relatively more open conformation of the N-terminal domain compared to the C-terminal counterpart.

Keywords: Bioinorganic chemistry, Sensors, Neuronal calcium sensor, Calcium displacement, Cerium