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A series of N -{ para -(ferrocenyl) ethynyl benzoyl} amino acid and dipeptide methyl and ethyl esters 4–18 were prepared by coupling para -(ferrocenyl) ethynyl benzoic acid 3 to the amino acids GABA(OMe), GABA(OEt) and the dipeptide esters GlyGly(OMe), GlyGly(OEt), Gly-L-Ala(OMe), Gly-L-Ala(OEt), Gly-D-Ala(OMe), Gly-D-Ala(OEt), Gly-L-Leu(OEt), Gly-L-Phe(OEt), SarGly(OMe), SarGly(OEt), Sar-L-Ala(OEt), L-ProGly(OEt) and L-Pro-L-Ala(OEt) using the standard N -(3-dimethylaminopropyl)- N’ -ethylcarbodiimide hydrochloride (EDC), 1-hydroxybenzotriazole (HOBt) protocol. All the compounds were fully characterized using a combination of I.R., UV-Vis, 1 H NMR, 13 C NMR, DEPT-135, 1 H- 13 C COSY (HMQC) spectroscopy and electrospray ionization mass spectrometry (ESI-MS). Selected compounds 5 , 7 , 9, 11, 16, 17 and 18 showed micromolar activity in the H1299 NSCLC cell line, with IC 50 values in the range of 3.8–8.3 μM.

The bioactivity of compounds is mainly dependent on molecular structure and the present work aims to explore the bonding features responsible for biological activity of novel anticancer drug N -(6-ferrocenyl-2-naphthoyl)-gamma-amino butyric acid ethyl ester (FNGABEE). In the present study, we investigate the molecular structural properties of newly synthesized title compound through experimental and quantum chemical studies. The detailed vibrational analysis has been performed using FT IR and FT Raman spectrum, aided by DFT computed geometry, vibrational spectrum, Eigen vector distribution and PED, at B3LYP/6-311 ++G(d,p) level. The resonance structure of naphthalene, different from that of benzene, revealed by molecular structure has been investigated using C C and C C stretching modes. The proton transfer in amide has been analyzed to obtain spectral distinction between different carbonyl and C N groups which point to the reactive sites responsible for binding with DNA and bovine serum albumin (BSA). The spectral distinction between eclipsed and staggered form of ferrocene has been analyzed. The molecular docking of FNGABEE with BSA and DNA has been performed to find the strength of binding and the moieties responsible for the interactions. The experimental binding studies of FNGABEE with BSA and DNA has been performed using UV absorption spectroscopy and fluorometric assay, to find the nature and strength of binding.

FT-Raman and FT-IR spectra of N-{(meta-ferrocenyl) Benzoyl} - l-alanine - glycine ethyl ester were recorded in solid phase. The optimized molecular geometry, the vibrational wavenumbers, the infrared intensities and the Raman scattering intensities were calculated by using density functional method(B3LYP) with 6-31G(d, p) basis set. Vibrational assignment of the molecule was done by using potential energy distribution analysis. Natural bond orbital analysis, Mulliken charge analysis and HOMO-LUMO energy were used to elucidate the reasons for intra molecular charge transfer. Docking studies were conducted to predict its anticancer activity.

The reactivity of ester group plays key role in inducing bioactivity of many ferrocenyl biconjugated compounds. The ester reactivity can be explained, based on electron transport mechanism using vibrational spectroscopy, aided by DFT simulation. The FT IR and FT Raman spectral measurements have been carried out for N-(6-ferrocenyl-2-naphthoyl)-L-alanine-glycine ethyl ester (FNLAGEE) and the optimized geometry and vibrational spectra have been computed using DFT method, at B3LYP/LANL2DZ level of theory. The cis conformation of ester and electron transport mechanism, thus analyzed, has been correlated to the geometry and the spectral characteristics of ester. To investigate the bioactivity and binding interactions of the molecule, molecular docking simulations and UV-Vis absorption studies of FNLAGEE with BSA and DNA has been performed.

The interaction of a drug with DNA and BSA play a great role in studying anti cancer activity and drug transport properties, which can be effectively, investigated using vibrational spectroscopy, UV visible spectroscopy and Fluorescence spectroscopy. The present work reports the structural features of N-(6-ferrocenyl-2-naphthoyl)-gamma-amino butyric acid Methyl ester (FNGABME) based on FTIR and FTRaman spectroscopy. The absorption and fluorescence spectroscopic methods were used to study the efficiency of the interaction of the compound FNGABME with BSA and DNA and also molecular docking were performed computationally to validate the results which shows that the title compound may exhibit inhibitory activity against the cancer cells.

1-Alkyl-1′- N - meta -(ferrocenyl) benzoyl dipeptide esters 7–18 and 1-alkyl-1′- N - ortho -(ferrocenyl) benzoyl dipeptide esters 19–30 were prepared by coupling the alkyl ferrocenyl benzoic acids 1–6 to the dipeptide ethyl esters Gly-Gly(OEt), Gly-L-Ala(OEt), Gly-L-Leu(OEt) and Gly-L-Phe(OEt) using the standard N -(3-dimethylaminopropyl)- N' -ethylcarbodiimide hydrochloride (EDC), 1-hydroxybenzotriazole (HOBt) protocol. The alkyl groups employed in the synthesis were methyl, ethyl and propyl. The compounds were characterized using a combination of 1 H NMR, 13 C NMR, DEPT-135 and 1 H- 13 C COSY (HMQC) spectroscopy and electrospray ionization mass spectrometry (ESI-MS). Selected compounds showed micromolar activity in the H1299 NSCLC cell line, with IC 50 values in the range of 2.6–20.1 μM.

1-Alkyl-1′- N - para -(ferrocenyl) benzoyl dipeptide esters 4 – 12 were prepared by coupling the alkyl ferrocenyl benzoic acids 1 – 3 to the dipeptide ethyl esters Gly- L -Ala(OEt), Gly- L -Leu(OEt) and Gly- L -Phe(OEt) using the standard N -(3-dimethylaminopropyl)- N’ -ethylcarbodiimide hydrochloride (EDC), 1-hydroxybenzotriazole (HOBt) protocol. All the compounds were fully characterized using a combination of 1 H NMR, 13 C NMR, DEPT-135 and 1 H– 13 C COSY (HMQC) spectroscopy, electrospray ionization mass spectrometry (ESI-MS) and cyclic voltammetry (CV). Selected compounds showed micromolar activity in the H1299 NSCLC cell line, with IC 50 values in the range of 4.5–6.6 μM.

N -{6-(Ferrocenyl) ethynyl-2-naphthoyl} amino acid and dipeptide ethyl esters 2 – 8 were prepared by coupling 6-(ferrocenyl) ethynyl-2-naphthoic acid 1 to the amino acid ethyl ester GABA(OEt) and the dipeptide ethyl esters GlyGly(OEt), GlyAla(OEt), SarGly(OEt), SarAla(OEt), ProGly(OEt) and ProAla(OEt) using the standard N -(3-dimethylaminopropyl)- N ′-ethylcarbodiimide hydrochloride (EDC), 1-hydroxybenzotriazole (HOBt) protocol. All the compounds were fully characterized using a combination of 1 H NMR, 13 C NMR, DEPT-135 and 1 H– 13 C COSY (HMQC) spectroscopy, electrospray ionization mass spectrometry (ESI-MS) and cyclic voltammetry (CV). Compounds, 2 – 8 showed micromolar activity in the H1299 NSCLC cell line, with IC 50 values in the range of 3.2–7.2 μM.

A series of N-(ferrocenylmethyl amino acid) fluorinated benzene-carboxamide derivatives 4b, 4c, 4d, 4e, 4f, 4g, 4h, 4i and 5b, 5c, 5d, 5e, 5f, 5g, 5h, 5i have been synthesized by coupling ferrocenylmethyl amine 3 with various substituted N-(fluorobenzoyl) amino acid derivatives using the standard N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride, 1-hydroxybenzotriazole protocol. The amino acids employed in this study were glycine and L-alanine. All of the compounds were fully characterized using a combination of 1H NMR, 13C NMR, 19F NMR, distortionless enhancement by polarization transfer (DEPT)-135, 1H–1H correlation spectroscopy (COSY) and 1H–13C COSY (heteronuclear multiple-quantum correlation) spectroscopy. The compounds were biologically evaluated on the oestrogen-positive MCF-7 breast cancer cell line. Compounds 4g, 4i, 5h and 5i exhibited cytotoxic effects on the MCF-7 breast cancer cell line. N-(Ferrocenylmethyl-L-alanine)-3,4,5-trifluorobenzene-carboxamide (5h) was the most active compound, with an IC50 value of 2.84 μm. Compounds 4i, 5h and 5i had lower IC50 values than that found for the clinically employed anticancer drug cisplatin (IC50 = 16.3 μm against MCF-7). Guanine oxidation studies confirmed that 5h was capable of generating oxidative damage via a reactive oxygen species-mediated mechanism. Copyright © 2013 John Wiley & Sons, Ltd.

4-N-Arylamino-1-butanol derivatives are produced via a palladium-catalyzed tetrahydrofuran ring-opening reaction. This reaction occurs during the reduction of aromatic nitro groups with polymethylhydrosiloxane (PMHS) and potassium fluoride in the presence of hydrogen peroxide. This represents a novel route for the synthesis of 4-N-arylamino-1-butanols.

In this article, we report the findings of a comprehensive structure-activity relationship study of N-(6-ferrocenyl-2-naphthoyl) dipeptide ethyl esters, in which novel analogues were designed, synthesized, and evaluated in vitro for antiproliferative effect. Two new compounds, 2 and 16, showed potent nanomolar activity in the H1299 NSCLC cell line, with exceptional IC(50) values of 0.13 and 0.14 μM, respectively. These compounds were also found to have significant activity in the Sk-Mel-28 malignant melanoma cell line (IC(50) values of 1.10 and 1.06 μM, respectively). Studies were also conducted to elucidate the mode of action of these novel organometallic anticancer compounds. Cell cycle analysis in the H1299 cell line suggests these compounds induce apoptosis, while guanine oxidation studies confirm that 2 is capable of generating oxidative damage via a ROS-mediated mechanism.

Standard peptide coupling reactions were use to prepare the N -(ferrocenyl) 2 and N -(ferrocenoyl) 2 cystine dimethyl ester derivatives 4 – 11 . The ferrocene carboxylic acids 1 and 3 were treated with 1-hydroxybenzotriazole (HOBt), N -(3-dimethylaminopropyl)- N ′-ethylcarbodiimide hydrochloride (EDC), l -cystine methyl ester hydrochloride and triethylamine in dichloromethane at 0 °C to furnish compounds 4 – 9 . The preparation of compounds 10 and 11 employed the dipeptide derivatives (glycine) 2 - l -cystine dimethyl ester and (β-alanine) 2 - l -cystine dimethyl ester respectively. The N -(ferrocenyl) 2 and N -(ferrocenoyl) 2 cystine dimethyl ester derivatives 4 – 11 , which are potential anion sensing agents, were spectroscopically characterized by a combination of 1 H NMR, 13 C NMR, IR, UV, DEPT-135 and 1 H– 13 C COSY (HMQC) spectroscopy, mass spectrometry and cyclic voltammetry. The electrochemical detection of dihydrogen phosphate and adenosine nucleotide anions in aqueous electrolyte by monolayers of { N -(ferrocenoyl)-β-alanine} 2 - l -cystine dimethyl ester 11 immobilized on gold electrodes using cyclic voltammetry is described. Immobilization of this receptor on a gold electrode surface enabled the recognition process to be detected in aqueous media. The recognition process is as a result of electrostatic interactions between the ferricenium cation and the anion, and hydrogen bonding interactions between the peptide amide bonds and the anion. The complexation process was amperometrically sensed via a reduction in the peak current of the ferrocene/ferricenium redox couple. A linear relationship ( R 2 = c. 0.99) was observed between anion concentration and change in peak current in both cases.

N-(3-Ferrocenyl-2-naphthoyl) dipeptide ethyl esters 1-4 and N-(6-ferrocenyl-2-naphthoyl) dipeptide ethyl esters 5-8 were prepared by coupling either 3-ferrocenylnaphthalene-2-carboxylic acid or 6-ferrocenylnaphthalene-2-carboxylic acid to the dipeptide ethyl esters GlyGly(OEt) (1, 5), AlaGly(OEt) (2, 6), GlyPhe(OEt) (3, 7) and GlyLeu(OEt) (4, 8), using the standard N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride, 1-hydroxybenzotriazole protocol. Electrospray ionization mass spectrometry (ESI-MS) and laser desorption ionization mass spectrometry (LDI-MS) were employed in conjunction with tandem mass spectrometry in the analysis of N-(3-ferrocenyl-2-naphthoyl) dipeptide ethyl esters 1-4 and N-(6-ferrocenyl-2-naphthoyl) dipeptide ethyl esters 5-8. Radical cations, [M](+•) and [M + H](+) species were both observed in the mass spectra. Intense sodium [M + Na](+) and potassium [M + K](+) adducts were also present. An important diagnostic ion at m/z [M-65](+) was observed in both the MS and MS/MS spectra of the N-(3-ferrocenyl-2-naphthoyl) dipeptide derivatives. Sequence-specific ions were generally not observed in the MS/MS spectra of the N-(3-ferrocenyl-2-naphthoyl) series due to formation of the diagnostic [M-65](+) ion. Sequence-specific ions were observed in the MS/MS spectra of the N-(6-ferrocenyl-2-naphthoyl) dipeptide esters with charge retention on the derivatized N-terminal of the dipeptide. Both series of compounds could be successfully analyzed by MALDI without the use of a matrix (LDI).

Resveratrol is a potential chemopreventive agent and can be isolated from grape skins and other dietary sources. The Wittig reaction and the decarbonylative Heck reaction were employed to synthesise analogues of this stilbene. Fluorinated derivatives of this stilbene were synthesised maintaining the 3,4',5-substitution pattern. The hydroxyl groups were also replaced by amino groups and the biological activity evaluated. The compounds were assayed on a variety of cell lines, primarily the non-small lung carcinoma cell line DLKP-A. Analogues were evaluated alone and in combination with a known chemotherapeutic agent epirubicin.

N -(3-ferrocenyl-2-naphthoyl) dipeptide esters ( 5–7 ) and N -(6-ferrocenyl-2-naphthoyl) dipeptide esters ( 8–10 ) were prepared by coupling either 3-ferrocenylnaphthalene-2-carboxylic acid 2 or 6-ferrocenylnaphthalene-2-carboxylic acid 4 to the dipeptide ethyl esters GlyAla(OEt) ( 5, 8 ), AlaGly(OEt) ( 6, 9 ), and AlaAla(OEt) ( 7, 10 ) using the standard N -(3-dimethylaminopropyl)- N ′-ethylcarbodiimide hydrochloride (EDC), 1-hydroxybenzotriazole (HOBt) protocol. All the compounds were fully characterized using a combination of 1 H NMR, 13 C NMR, DEPT-135 and 1 H- 13 C COSY (HMQC) spectroscopy, electrospray ionization mass spectrometry (ESI-MS) and cyclic voltammetry (CV). In vitro , the cytotoxic effects of compounds 5–10 show improvements over the corresponding N -(ferrocenyl)benzoyl derivatives, with IC 50 values against the H1299 lung cancer cells ranging from 1.2 μM to 8.0 μM. N -(6-ferrocenyl-2-naphthoyl)-glycine- l -alanine ethyl ester 8 was found to be the most active derivative of the naphthoyl series so far, displaying an IC 50 value of 1.3 ± 0.1 μM. This value is slightly lower than that found for the clinically employed anti-cancer drug cisplatin (IC 50 = 1.5 ± 0.1 μM against H1299).

N - ortho, meta and para -(ferrocenyl)benzoyl dipeptide esters 2–10 were prepared by coupling ferrocenyl benzoic acids 1 (ortho, meta and para) to the dipeptide ethyl esters GlyAbu(OEt) 2–4 , GlyNva(OEt) 5–7 and GlyNle(OEt) 8–10 in the presence of N -(3-dimethylaminopropyl)- N′ -ethylcarbodiimide hydrochloride and 1-hydroxybenzotriazole. The compounds were fully characterized by a range of NMR spectroscopic techniques, mass spectrometry and cyclic voltammetry. The cytotoxicity of 3, 6 and 9 versus H1299 lung cancer cells were 10.5 μM, 19.1 μM and 18.9 μM, respectively, whereas N -{ meta -(ferrocenyl)-benzoyl}-glycine- l -alanine ethyl ester 11 and N -{ para -(ferrocenyl)-benzoyl}-glycine- l -alanine ethyl ester 12 gave IC 50 values of 4.0 and 6.6 μM, respectively. Therefore, an increase in alkyl chain length of the second amino acid also increases the IC 50 values. Cell cycle analysis of N -{ ortho -(ferrocenyl)-benzoyl}-glycine- l -alanine ethyl ester 13 suggests a block in the G2/M phase of the cell cycle.

A series of novel ferrocene-based receptors, 1,1'-N,N'-ferrocenoylbisamino acid methyl esters 2-5 have been prepared and their electrochemical properties determined. The amino acids employed were glycine (2), beta-alanine (3), gamma-aminobutyric acid (4) and l-norleucine (5). These receptors are composed of an electroactive core and two parallel strands of amino acids that can interact with anions via electrostatic interactions in the oxidized state as well as secondary interactions, such as hydrogen bonding and hydrophobic interactions. Furthermore, the semi-rigid molecular clefts between the two strands of amino acids in these receptors are capable of discerning anions of different geometries and sizes. The anion sensing capabilities of receptors 2-5 were studied using cyclic voltammetry (CV). The anions studied were chloride (Cl-), nitrate (NO3-), dihydrogen phosphate (H(2)PO(4)-), hydrogen sulfate (HSO(4)-), acetate (CH(3)COO-) and neurologically important anions such as lactate (CH(3)CH(OH)COO-), pyruvate (CH(3)COCOO-) and glutamate (HOOC-CH(NH2)CH(2)CH(2)COO-). The receptors 2-5 exhibit selectivity towards chloride, dihydrogen phosphate and acetate, over hydrogen sulfate and nitrate ions and generate a redox response in organic media. Also, binding studies of receptor 3 with neurologically important anions show it displays selectivity towards lactate and pyruvate, over glutamate ions and generates a redox response. However the response is ill defined in all cases, with poorly separated "free" and "ion-pair" peaks, which preclude accurate measurement of the response by CV. These results emphasize the considerations required for the design of ferrocene-based receptors and the necessary parameters for efficient electrochemical recognition of small anions by CV.

N-ortho-ferrocenyl benzoyl dipeptide esters 2–6 were prepared by coupling ortho-ferrocenyl benzoic acid 1 to the dipeptide ethyl esters GlyGly(OEt) (2), GlyAla(OEt) (3), GlyPhe(OEt) (4), AlaGly(OEt) (5) and AlaPhe(OEt) (6). The compounds were fully characterized by a range of NMR spectroscopic techniques, mass spectrometry and cyclic voltammetry. The cytotoxicity of 3 and 5 towards lung cancer cells has been determined.

A series of N -(ferrocenylmethyl)benzene-carboxamide derivatives ( 4a – f ) have been synthesised by coupling ferrocenylmethyl amine 3 with benzoic acid and various substituted fluorobenzoic acids using the standard 1,3-dicyclohexylcarbodiimide (DCC), 1-hydroxybenzotriazole (HOBt) protocol. All compounds were fully characterised using a combination of 1 H NMR, 13 C NMR, 19 F NMR, DEPT-135, 1 H– 1 H COSY and 1 H– 13 C COSY (HMQC) spectroscopy and electrospray ionisation mass spectrometry (ESI-MS). The compounds 4a , 4d , 4e and 4f exhibited cytotoxic effects on the MDA-MB-435-S-F breast cancer cell line. Single crystal X-ray crystallographic data for 4d is also presented.

N-para-ferrocenyl benzoyl dipeptide esters 2–5 were prepared by coupling para-ferrocenyl benzoic acid 1 to the dipeptide ethyl esters GlyGly(OEt) 2, GlyAla(OEt) 3, GlyLeu(OEt) 4 and GlyPhe(OEt) 5. The compounds were fully characterized by a range of NMR spectroscopic techniques, mass spectrometry (ESI-MS, FABMS, MS/MS) and cyclic voltammetry (CV). The a1 and b1 ions appeared at one mass unit less than the expected mass in the tandem mass spectra. The CV curves of compounds 2–5 exhibited quasi-reversible redox behavior similar to the Fc/Fc+ redox couple and displayed oxidation potential values in the 50–55 mV range, against the Fc/Fc+ redox couple.

A series of N - para -ferrocenyl benzoyl dipeptide esters 2 – 5 were prepared by coupling para -ferrocenyl benzoic acid ( 1 ) to the dipeptide ethyl esters using the conventional 1,3-dicyclohexylcarbodiimide (DCC), 1-hydroxybenzotriazole (HOBt) protocol. The dipeptides employed in the synthesis were Ala-Gly(OEt) ( 2 ), Ala-Ala(OEt) ( 3 ), Ala-Leu(OEt) ( 4 ) and Ala-Phe(OEt) ( 5 ). The compounds were fully characterized by a range of NMR spectroscopic techniques, electrospray ionization mass spectrometry (ESI-MS) and tandem mass spectrometry (MS/MS). In addition the X-ray crystal structure of the l -alanine-glycine derivative 2 has been determined.

A series of novel N-meta-ferrocenyl benzoyl dipeptide esters (2–5) have been prepared by coupling meta-ferrocenyl benzoic acid (1) to the dipeptide ethyl esters using the conventional 1,3-dicyclohexylcarbodiimide (DCC), 1-hydroxybenzotriazole (HOBt) protocol. The dipeptides employed were GlyGly(OEt) (2), GlyAla(OEt) (3), GlyLeu(OEt) (4) and GlyPhe(OEt) (5). The compounds were fully characterized by a range of NMR spectroscopic techniques and by mass spectrometry (MALDI-MS, ESI-MS).

A series of N - ortho -ferrocenyl benzoyl amino acid ethyl esters 3 – 9 have been prepared by coupling ortho -ferrocenyl benzoic acid 2 to the amino acid ethyl esters of glycine, l -alanine, l -leucine, l -phenylalanine, β-alanine, 4-aminobutyric acid and (±)-2-aminobutyric acid using the conventional 1,3-dicyclohexylcarbodiimide, 1-hydroxybenzotriazole protocol. The compounds were fully characterized by a range of NMR spectroscopic techniques and by mass spectrometry (MALDI-MS, ESI-MS). The X-ray crystal structure of the l -phenylalanine derivative 6 has been determined.

The structure of fampridine (EL-970) or 4-amino­pyridine, C5H6N2, has been redetermined at 150 K. The room-temperature structure has been reported previously [Chao & Schempp (1977). Acta Cryst. B33, 1557–1564]. Pyramidalization at the amine N atom occurs in fampridine, with the N atom 0.133 (11) A from the plane of the three C/H/H atoms to which it is bonded; the inter­planar angle between the pyrid­yl ring and NH2 group is 21 (2)°. Aggregation in the solid state occurs by N—H⋯N and N—H⋯π(pyridine) inter­actions with N⋯N and N⋯π(centroid) distances of 2.9829 (18) and 3.3954 (15) A, respectively; a C—H⋯π(pyridine) contact completes the inter­molecular inter­actions [C⋯π(centroid) = 3.6360 (16) A].

A series of N-para-ferrocenyl benzoyl amino acid ethyl esters 1–8 have been prepared by coupling para-ferrocenyl benzoic acid with the amino acid esters using the conventional 1,3-dicyclohexylcarbodiimide (DCC), 1-hydroxybenzotriazole (HOBt) protocol. The amino acids employed in the synthesis were glycine, l -alanine, l -leucine, l -phenylalanine, β-alanine, 4-aminobutyric acid, (±)-2-aminobutyric acid and 2-aminoisobutyric acid. The compounds were fully characterized by a range of spectroscopic techniques such as NMR and mass spectrometry. In addition the X-ray crystal structures of the glycyl 1 and (±)-2-aminobutyrate 7 derivatives have been determined. Analysis of relevant fragments in crystal structures on the Cambridge Structural Database indicates a relative paucity of common fragments such as the α-aminobutyrate group in comparison to the glycyl moiety.

The N-ferrocenoyl amino acid ester derivatives FcCOR {Fc=(η5-C5H5)Fe(η5-C5H4)} where R=Gly(OMe) 1, Gly(OEt) 2, Gly(OBn) 3, l -Ala(OMe) 4, l -Ala(OEt) 5, l -Leu(OMe) 6, l -Leu(OEt) 7, l -Leu(OBn) 8, l -Phe(OMe) 9 and l -Phe(OEt) 10, were prepared by coupling ferrocene carboxylic acid with the appropriate amino acid ester starting materials using the 1,3-dicyclohexylcarbodiimide (DCC), 1-hydroxybenzotriazole (HOBt) protocol and these have been characterised by spectroscopic techniques. The electrochemical anion sensing behaviour of compounds 1–10 with several anions using a platinum microdisk working electrode is described, together with 1H NMR anion complexation studies. The X-ray single crystal structure of N-ferrocenoyl- l -alanine methyl ester 4 has been determined and contains two molecules which differ slightly in conformation in the asymmetric unit of space group P21 (No. 4); principal dimensions are amide N(H)CO 1.224(6) and 1.231(6) A, ester CO 1.220(10) and 1.190(7) A, with N–H⋯OC(amide) as the primary intermolecular hydrogen bond, N⋯O 2.992(6) and 2.971(6) A and with graph set C(4).

A series of N-para-(ferrocenyl)benzoyl amino-acid esters, para-Fc(C6H4)CONHCH(R)CO2CH3 {Fc = (η5-C5H5)Fe(η5-C5H4); R = H, CH3, CH2CH(CH3)2, CH2C6H5}, 3–6 have been prepared by coupling para-(ferrocenyl)benzoic acid to the amino-acid esters (gly, l -Ala, l -Leu, l -Phe) using the standard 1,3-dicyclohexylcarbodiimide (DCC), 1-hydroxybenzotriazole (HOBt) protocol. The compounds were fully characterized by a range of spectroscopic techniques including FAB-MS. The X-ray crystal structures of the parent para-(ferrocenyl)benzoyl methyl ester, Fc-C6H4CO2Me, 1 and a chiral derivative N-{para-(ferrocenyl)benzoyl}- l -alanine methyl ester, Fc-C6H4CONHCH(CH3)CO2Me, 4 have been determined.

The title compound, C 19 H 27 N 3 O 2 , crystallizes in space group P1 with two molecules in the asymmetric unit which differ slightly in conformation. Intermolecular N-H...N and C-H...O interactions generate a hydrogen-bonded ring system between the alternating molecules, graph set R 2 2 (16), with N...N distances of 3.021 (3) and 3.041 (3) A, and C...O distances of 3.219(3) and 3.296 (3) A along the hydrogen-bonded chains.

The title compound, benzyl N-(ferrocenecarbonyl)glycinate, [Fe(C 5 H 5 )(C 15 H 14 NO 3 )] a glycine benzyl ester derivative, is an effective anion sensor for electrochemically sensing the dihydrogen phosphate anion (H 2 PO 4 - ). Intermolecular N-H...O hydrogen bonds form one-dimensional chains with graph set C(4) [N...O 2.811 (3) A]. A two-dimensional network is formed by linking the chains through C ar -H...O=C ester interactions about inversion centres [graph set R 2 2 (14); C...O 3.406 (4) A]. An intramolecular C Cp -H...O=C ester interaction [C...O 3.540 (3) A] with graph set S(9) completes the hydrogen bonding.

The synthesis of six N -ferrocenoyl dipeptide ester derivatives FcCOR (Fc=( η 5 -C 5 H 5 )Fe( η 5 -C 5 H 4 ); R=Gly-Gly(OMe) ( 1 ), Leu-Leu(OEt) ( 2 ), Ala-Phe(OEt) ( 3 ), Phe-Phe(OMe) ( 4 ), Phe-Leu(OBn) ( 5 ) and Phe-Ser(OEt) ( 6 )) is described. The electrochemical anion sensing behaviour (using a platinum microdisk working electrode) and 1 H NMR anion coordination studies of these novel pendant N -ferrocenoyl dipeptide ester derivatives with a range of anions are reported.

The title compound, [Fe(C5H5)(C12H10NO3S)], was synthesized from ferrocenecarboxylic acid and methyl 2-amino­thio­phene-3-carboxyl­ate in modest yield. The substituted ring system is essentially planar through the amido­thienylcarboxyl­ate moiety, η5-(C5H4)CONH(C4H2S)CO2Me, with the amido unit at an angle of 3.60 (7)° to the five-atom thienyl group, which is oriented at an angle of 3.17 (7)° to the ester moiety. The primary hydrogen bond is an intramolecular N—H⋯O=Ccarboxyl­ate interaction [N⋯O 2.727 (2) A], and the main intermolecular hydrogen bond involves a thienyl carboxyl­ate and the carboxyl­ate of a symmetry-related molecule [C⋯O 3.443 (3) A].

4-N-Arylamino-1-butanol derivatives are produced via a palladium-catalyzed tetrahydrofuran ring-opening reaction. This reaction occurs during the reduction of aromatic nitro groups with polymethylhydrosiloxane (PMHS) and potassium fluoride in the presence of hydrogen peroxide. This represents a novel route for the synthesis of 4-N-arylamino-1-butanols.

The title compound, [Fe(C₅H₅)(C₂₁H₁₆NO)], was synthesized from the coupling reaction of anthracene-9-carboxylic acid and ferrocenylmethylamine. The ferrocenyl (Fc) group and the anthracene ring system both lie approximately orthogonal to the amide moiety. An amide-amide interaction (along the a axis) is the principal interaction [N...O = 2.910 (2) A]. A C-H...π(arene) interaction [C...centroid = 3.573 (2) A] and a C-H...O interaction [C...O = 3.275 (3) A] complete the hydrogen bonding; two short (Fc)C...C(anthracene) contacts are also present.

The title compounds, [Fe(C(5)H(5))(C(14)H(13)O(2))] and [Fe(C(5)H(5))(C(15)H(15)O(2))], respectively, contain the ferrocenyl eta(5)(C(5)H(4)) and phenylene -C(6)H(4)- rings in a nearly coplanar arrangement, with interplanar angles of 6.88 (12) and 10.5 (2) degrees, respectively. Molecules of the ethyl ester form dimers through eta(5)(C(5)H(5))C-H...O=C hydrogen bonds, with graph set R(2)(2)(20), and, together with Csp(3)-H.pi(C(5)H(5)) interactions, generate a one-dimensional column (irregular ladder). Molecules of the isopropyl ester aggregate through eta(5)(C(5)H(5))C-H.pi(C(6)H(4)) interactions.

Tandem mass spectrometry (MS/MS) is an attractive technique for sequencing membrane proteins because it can be applied to peptides in mixtures that are difficult to separate chromatographically. To evaluate the suitability of MS/MS sequencing for membrane proteins and to develop protocols for the preparation of the cleaved peptides, we employed the well characterized apoproteins of bacteriorhodopsin and bovine rhodopsin, i.e. bacterioopsin and opsin, respectively. Without separation, nine out of ten peptides resulting from cyanogen bromide cleavage of bacterioopsin were detected by fast atom bombardment MS, the single undetected fragment being a tetrapeptide that was presumably hidden in the low-m/z matrix background. Furthermore, MS/MS was used to confirm the sequence of all the peptides detected with m/z values below 3.5 kDa (40% of the protein). Bovine opsin was analyzed in a similar fashion. Tandem MS/MS has thus allowed the sequencing of substantial portions of two integral membrane proteins by the analysis of unseparated peptide mixtures, demonstrating for the first time that this technique can obviate some of the most serious difficulties associated with sequencing membrane proteins, namely the difficult-to-achieve separation of the ‘sticky’ peptide fragments.

A series of N-(ferrocenyl)naphthoyl amino acid esters 5-18 has been prepared by coupling ferrocenyl naphthoic acids 3-4 to alpha-amino acids and linear amino acids in the presence of N-(3-dimethylaminopropyl)-N'-ethylcarbodiimide hydrochloride (EDC) and 1-hydroxybenzotriazole (HOBt). The compounds were fully characterised by a range of NMR spectroscopic techniques, UV-Vis spectroscopy, mass spectrometry and cyclic voltammetry. X-ray crystallographic studies of the intermediate compounds 1-2 were also performed. Biological evaluation of the intermediates 1-2 and N-(ferrocenyl)naphthoyl amino acid esters 5-18 was performed in the H1299 non-small cell lung cancer (NSCLC) cell line and the Sk-Mel-28 metastatic melanoma cell line. The intermediates 1-2 failed to produce an effect in either cell line. Compounds 5-18 exhibited a strong anti-proliferative effect in the H1299 cell line, whilst the Sk-Mel-28 cells were slightly more resistant to these compounds. N-(6-ferrocenyl-2-naphthoyl)-gamma-aminobutyric acid ethyl ester 17 shows a particularly high activity in both the H1299 cell line (IC(50) = 0.62 +/- 0.07 microM) and the Sk-Mel-28 cell line (IC(50) = 1.41 +/- 0.04 microM).

1. An FMRFamide-related decapeptide isolated from the anterior byssus retractor muscle (ABRM) of the bivalve mollusc, Mytilus edulis, was shown to have D-Leu as the second amino acid residue. 2. The excitatory effects of the peptide (Mytilus-FFRFamide) on the ABRM were not changed appreciably by substituting an L-Leu residue for the D-Leu residue.

1. Ten peptides that showed an inhibitory effect on phasic contraction of the ABRM of Mytilus were isolated from the ganglia of the African giant snail, Achatina fulica. 2. Seven of the peptides were shown to be hexapeptides having -Pro-Xaa-Phe-Val-NH2 as a common structure, which was previously shown to be a characteristic of Mytilus inhibitory peptides (MIPs). 3. The remaining three were pentadecapeptides, each of which consisted of two MIP-related hexapeptides linked by -Gly-Arg-Arg-.

Cathepsins are known to have many important physiological roles and provide a viable target for inhibition. Fluorobenzoyl dipeptide derivatives were synthesized and tested for biological activity in an effort to find an efficient inhibitor of the cysteine protease cathepsin L. Thirty-six novel inhibitors (1-36) were synthesized from protected amino acids via the standard DCC/HOBt coupling protocol, containing a benzyl ester or a nitrile as an electrophilic warhead. The activity of the inhibitors was evaluated against cathepsin L and IC50 values calculated. Modification of both amino acids and terminal groups afforded compounds with single digit micromolar inhibition. Results utilizing the benzoyl-L-leucine-glycine nitrile backbone are comparable to that for the commercially available inhibitor 39. © 2010 Informa UK Ltd.

N-Ferrocenoyl glycine ester derivatives FcCONHCH2COOR (Fc=(η5-C5H5)Fe(η5-C5H4); R=methyl (1), ethyl (2) and benzyl (3)) have been prepared by coupling ferrocene carboxylic acid to a series of glycine esters using 1,3-dicyclohexylcarbodiimide (DCC), 1-hydroxybenzotriazole (HOBT) and Et3N in CH2Cl2. The electrochemical anion sensing using a platinum microdisk working electrode of these N-ferrocenoyl glycine ester derivatives is reported. The crystal structure of 1 has been determined; principal dimensions are amide N(H)CO 1.229(3) A, ester CO 1.183(3) A with N–H⋯OC(amide) as the primary intermolecular hydrogen bond, N⋯O 2.804(3) A.

The title compound, C₁₇H₁₅NO₃, forms a hydrogenbonded network in the solid state consisting of O-H...O=C, Carene--H...and 0=C and Carene--H...πarene intermolecular interactions, with shortest O...O, C...O and C...C distances of 2.625(2), 3.281(3) and 3.652 (3)A, respectively. The interplanar angle between the five- and six-membered rings of the isoindole system is 1.07 (14) °, with the carbonyl O atom 0.I10 (3)A from the C₄N ring plane.

The conformations and hydrogen bonding in the thiophene and thiazole title compounds, [Fe(C5H5)(C20H14NO3S)], (I), and [Fe(C5H5)(C19H17N2O3S)], (II), are discussed. The sequence (C5H4)-(C6H4)-(CONH)-(C4H2S)-(CO2Me) of rings and moieties in (I) is close to being planar; all consecutive interplanar angles are less than 10 degrees . An intramolecular N-H...O=C(ester) hydrogen bond [graph set S6, N...O = 2.768 (2) A and N-H...O = 134 (2) degrees ] effects the molecular planarity, and aggregation occurs via hydrogen-bonded chains formed from intermolecular C(ar)-H...O=C(ester/amide) interactions along [010], with C...O distances ranging from 3.401 (3) to 3.577 (2) A. The thiazole system in (II) crystallizes with two molecules in the asymmetric unit; these differ in the conformation along their long molecular axes; for example, the interplanar angle between the phenylene (C6H4) and thiazole (C3NS) rings is 8.1 (2) degrees in one molecule and 27.66 (14) degrees in the other. Intermolecular N-H...O=C(ester) hydrogen bonds [N...O = 2.972 (4) and 2.971 (3) A], each augmented by a C(phenylene)-H...O=C(ester) interaction [3.184 (5) and 3.395 (4) A], form motifs with graph set R2(1)(7) and generate chains along [100]. The amide C=O groups do not participate in hydrogen bonding. Compound (II) is the first reported ferrocenyl-containing thiazole structure.

The mechanism for the formation of y ions in the collision-induced dissociation (CID) spectra of protonated peptides produced by fast-atom bombardment was investigated by tandem mass spectrometry and deuterium labelling studies. The results show that a hydrogen atom attached to nitrogen and not to carbon migrates during cleavage of the amide bond. A mechanism based on these results is presented.

Several novel applications of 2-hydroxyethyl disulphide as a matrix material in liquid secondary-ion mass spectrometry are presented. This matrix is superior to the conventional glycerol matrix for the analysis of peptides with hydrophobic residues. It was found to be an excellent matrix for the analysis of a wide range of other compounds. It is chemically inert, enhances the formation of [M + Na]+ and [M + K]+ adducts and gives few ions above m/z 300.

Four hypotensive peptides called elapherine-A, -B, -C and -D were isolated from the body of Elaphe climacophora after removal of the internal organs. Elapherine-A, which had the lowest molecular weight, exhibited a prolonged fall for 5 min in the blood pressure of spontaneously hypertensive rats, whereas elapherin-B, -C and -D displayed a transient fall in the blood pressure. The molecular weights of elapherine-A---D estimated from sodium dodecyl sulfate (SDS) gel disk electrophoresis were 6600, 6900, 7000 and 7200, respectively. The isoelectric points of these peptides were 10.4, 10.6, 10.7 and 10.5, respectively. They possessed a single polypeptide chain of 34-35 (elapherine-A), 56-58 (elapherine-B), 56-57 (elapherine-C) and 52-53 (elapherine-D) amino acid residues.