Ferrocene-dipeptide conjugates derived from aminoferrocene and 1-acetyl-1′-aminoferrocene: synthesis and conformational studies

Kovač, Veronika; Semenčić, Mojca Čakić; Kodrin, Ivan; Roca, Sunčica; Rapić, Vladimir

doi:10.1016/j.tet.2013.09.048

Cited by 23 publications

(44 citation statements)

References 35 publications

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“…48 In addition, the earlier described L-Ala containing bioorganometallics 1, 2 and 3a displayed the positive Cotton effect attributed to the righthanded helicity. 48 In addition, the earlier described L-Ala containing bioorganometallics 1, 2 and 3a displayed the positive Cotton effect attributed to the righthanded helicity.…”

Section: Compoundmentioning

confidence: 85%

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The conjugates of ferrocene-1,1′-diamine and amino acids. A novel synthetic approach and conformational analysis

et al. 2015

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A novel synthetic approach toward a poorly explored bioorganometallic consisting of ferrocene-1,1'-diamine bearing structurally and chirally diverse amino acid sequences is reported. Until now, ferrocene-1,1'-diamine was suitable for accommodating only identical amino acid sequences at its N-termini, leading to the symmetrically disubstituted homochiral products stabilized through a 14-membered intramolecular hydrogen-bonded ring as is seen in antiparallel β-sheet peptides. The key step of the novel synthetic pathway is the transformation of Ac-Ala-NH-Fn-COOH (5) (Fn = 1,1'-ferrocenylene) to orthogonally protected Ac-Ala-NH-Fn-NHBoc (7). The spectroscopic analysis (IR, NMR, CD) of the novel compounds, corroborated with DFT studies, suggests the interesting feature of the ferrocene-1,1'-diamine scaffold. The same hydrogen-bonding pattern, i.e. a 14-membered hydrogen-bonded ring, was determined both in solution and in the solid state, thus making them promising, yet simple scaffolds capable of mimicking β-sheet peptides. In vitro screening of potential anticancer activity in Hep G2 human liver carcinoma cells and Hs 578 T human breast cancer cells revealed a cytotoxic pattern for novel compounds (150-500 μM) with significantly decreased cell proliferation.

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Section: Compoundmentioning

confidence: 85%

“…13,48,54 Herein, we have decided to use the same approach to [c] Cg1 is centroid of the C6-C10 ring. 13,48,54 Herein, we have decided to use the same approach to [c] Cg1 is centroid of the C6-C10 ring.…”

Section: Computational Study Of 3a 3b and 3cmentioning

confidence: 99%

The conjugates of ferrocene-1,1′-diamine and amino acids. A novel synthetic approach and conformational analysis

et al. 2015

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“…NaN 3 ,L iOH, [D 6 ]DMSO (Sigma-Aldrich); HOBt, HBTU, EDC·HCl, BocÀl-AlaÀOH, BocÀd-AlaÀOH, HÀl-ProÀOH and HÀd-ProÀOH (Advanced ChemTech);S OCl 2 (Alfa Aesar) and 2picolinic acid (Sigma-Aldrich) were used as received (compounds 18-26). BocÀAlaÀOH was activated by coupling reagents HBTU/HOBt for 2h in CH 2 Cl 2 and then coupled to ProÀOMe, after which, the resulting product BocÀAlaÀProÀ OMe was hydrolyzed by using LiOH (compounds [18][19][20][21][22][23][24][25][26]. The syntheses of BocÀProÀNHÀFnÀCOOMe (1) had been previously described.…”

Section: Methodsmentioning

confidence: 99%

“…Conversely,t he slow proline isomerization keeps the peaks resolved at higher temperatures. [39] The former studies on ferrocene peptides revealed that the introductiono ft he ferrocene moiety into the chiral peptidei nducedi ntramolecular hydrogen-bonds between two podandp eptide strands [3][4][5]13] or within the same peptides trand, [12,16,18,19] which increases the intensityo ft he spectralb ands at 480 nm. The minimallyt emperature-affected amide resonanceso fh omochiral peptides 14 and 16 might account for the isomer locking that was induced by the proposed participation in strong hydrogen bonds( see the Supporting Information, Figures S151a-e).…”

Section: Conformational Analysis By Ir Nmr and CD Spectroscopymentioning

confidence: 99%

“…[37b] The closer inspection of temperature-dependent NMR data revealed that the amide resonances of heterochiral conjugates 15 and 17 underwent coalescence to some extent upon heating, which is an additional confirmation of their involvement in somewhat weaker hydrogen bonds. [4b] It is worth emphasizing the appreciable decrease in CD activity of desymmetrized analogues of peptides II (BocÀProÀNHÀFnÀCOOMe (1)a nd AcÀProÀNHÀFnÀCOOMe (IIa), [13] M q % 500 deg cm 2 dmol À1 ;B ocÀAlaÀAlaÀNHÀFnÀCOMe (IIb), [19] M q % 2000 deg cm 2 dmol À1 ), which are structurally predisposed to form as ingle intrastrand hydrogen bond. Moreover,u pon heatingf rom 233 to 313 K, the peaks that corresponded to trans/trans, cis/trans, trans/cis,a nd cis/cis states of peptides 21-24 (see the Supporting Information, Figures S115, S120, S126, S136) did not completely coalesce, which indicates that the slow isomerization owing to strong hydrogen bonds is capable of inducing isomer locking.…”

Section: Conformational Analysis By Ir Nmr and CD Spectroscopymentioning

confidence: 99%

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Helically Chiral Peptides That Contain Ferrocene‐1,1′‐diamine Scaffolds as a Turn Inducer

Kovačević

Kodrin

Roca

et al. 2017

Chemistry A European J

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A series of peptides that contain homo- and heterochiral Ala-Pro sequences attached to the turn-inducing ferrocene-1,1'-diamine scaffold were synthesized. The effects of the backbone chirality and the N-terminal group (Boc/Ac) on the conformational properties of the novel peptidomimetics were thoroughly explored by IR, NMR, and CD spectroscopy and the experimental observations were corroborated by DFT studies in solution. The most stable conformers of the homochiral peptides adopted the interstrand hydrogen-bond patterns, realized through ten- and thirteen-membered rings. The common feature of the most stable conformers of the heterochiral peptides was the adoption of the turn-like structures that feature the simultaneous intra- (seven-membered) and interstrand (sixteen-membered) hydrogen-bonded rings. An exchange of two N-terminal groups had a somewhat larger influence on the distribution of the hydrogen-bond patterns in homochiral than in heterochiral derivatives. The homochiral peptides that contain pyridine moieties as metal coordination sites formed 1:1 complexes with divalent metal ions, which included Zn , Cd , Cu and Fe .

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Synthesis and structure analysis of ferrocene‐containing pseudopeptides

et al. 2018

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Ferrocene with its aromaticity and facile redox properties is an attractive moiety to be incorporated into functional moieties. Medicinal applications of ferrocene are well known and ferrocene itself shows cytotoxic and antianemic properties. In this article, we will describe the synthesis and the structure analysis of two pseudopeptides containing a ferrocene moiety as N-terminal group. After purification, Fc-l-Phe-d-Oxd-OBn [l-Phel-phenylalanine; d-Oxd(4R,5S)-4-Methyl-5-carboxy-oxazolidin-2-one] appears as bright brown solid that spontaneously forms brown needles. The X-ray diffraction of the crystals shows the presence of strong π interactions between the ferrocenyl moiety and the phenyl rings, while no NH•••OC hydrogen bonds are formed. This result is confirmed by FT-IR and H NMR analysis. In contrast, both FT-IR and H NMR analysis suggest that Fc-(l-Phe-d-Oxd) -OBn forms a turn conformation stabilized by intramolecular NH•••OC hydrogen bonds in solution. Chiroptical spectroscopies (ECD and VCD) substantially confirmed the absence of a well-defined folded structure. The presence of the Fc moiety is responsible for specific ECD signals, one of which displayed pronounced temperature dependence and is directly related with the helicity assumed by the Fc core. Solid-state ECD spectra were recorded and rationalized on the basis of the X-ray geometry and quantum-mechanical calculations.

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Ferrocene-dipeptide conjugates derived from aminoferrocene and 1-acetyl-1′-aminoferrocene: synthesis and conformational studies

Cited by 23 publications

References 35 publications

The conjugates of ferrocene-1,1′-diamine and amino acids. A novel synthetic approach and conformational analysis

The conjugates of ferrocene-1,1′-diamine and amino acids. A novel synthetic approach and conformational analysis

Helically Chiral Peptides That Contain Ferrocene‐1,1′‐diamine Scaffolds as a Turn Inducer

Synthesis and structure analysis of ferrocene‐containing pseudopeptides

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