133587-10-7

Usage

Type of Compound

Synthetic chemical compound

Fields of Application

Coordination chemistry and bioinorganic chemistry

Classification

Macrocyclic ligand

Metal Ion Complex Formation

Highly stable with metal ions such as copper, zinc, and cadmium

Medical Imaging

Due to its ability to chelate metal ions and form stable complexes

Targeted Drug Delivery

For the same reason as medical imaging

Environmental Chemistry

Due to its selective binding properties

Analytical Chemistry

For the same reason as environmental chemistry

Versatility

Wide range of potential uses in various fields of science and technology

Upstream product

• 175854-39-4 1,4,7-tris(tert-butyloxycarbonyl)-1,4,7,10-tetraazacyclododecane 
• 626-15-3 1,3-bis-(bromomethyl)benzene 
• 94530-07-1 1,4,7-tris-(4-tolylsulphonyl)-1,4,7,10-tetraazacyclododecane 
• 294-90-6 1,4,7,10-tetraazacyclododecan 
• 188903-14-2 1-benzyloxycarbonyl-4,7,10-tris-tert-butoxycarbonyl-1,4,7,10-tetraazacyclododecane 
• 289685-84-3 1,4,7-tricarbaldehyde-1,4,7,10-tetraazacyclododecane 
• 74199-09-0 cyclen-glyoxal 
• 74199-09-0 cis-13-1,4,7,10-tetraazatetracyclo<5.5.2.0^4,140^10,13>tetradecane 

Downstream Products

• 1073314-27-8 1,3-bis[1-(4,7,10-tris(carbamoylmethyl)-1,4,7,10-tetraazacyclododecane)]-m-xylene 

Relevant academic research and scientific papers

Unexpected aggregation of neutral, xylene-cored dinuclear GdIII chelates in aqueous solution

We have synthesized ditopic ligands L1, L2, and L3 that contain two DO3A3- metal-chelating units with a xylene core as a noncoordinating linker (DOSA3- = 1,4,7,10-tetraazacyclododecane-1,4,7-triacetat

Steric Effects on the Binding of Phosphate and Polyphosphate Anions by Zinc(II) and Copper(II) Dinuclear Complexes of m-Xylyl-bis-cyclen

The triethylbenzene-bis-cyclen (cyclen = 1,4,7,10-tetraazacyclododecane) compound (tbmce) was designed with an imposed structural rigidity at the m-xylyl spacer to be compared to a less restrained and known parent compound (bmce). The framework of both co

A tris(Zn(II)-1,4,7,10-tetraazacyclododecane) complex as a new receptor for phosphate dianions in aqueous solution

A new tris(Zn(II)-cyclen) (Zn3L3), which has three Zn(II)-macrocyclic tetraamine (cyclen) complexes connected through a 1,3,5-trimethylbenzene spacer, has been synthesized as a novel receptor for organic phosphate dianions in aqueous solution (cyclen = 1,4,7,10-tetraazacyclododecane and L3 = 1,3,5-tris(1,4,7,10-tetraazacyclododecan-1-ylmethyl)benzene). The design of Zn3L3 was based on X-ray crystal structure analysis of the 1:3 complex of 4-nitrophenyl phosphate (NPP2-) with Zn(II)-cyclen (ZnL1) complex. The potentiometric pH titration of Zn3L3.3H2O revealed the deprotonation constants of the three Zn(II)-bound H2O molecules to be 6.1 (pK1), 7.3 (pK2), and 8.6 (pK3) at 25 °C with I = 0.1 (NaNO3). These three stepwise deprotonations and 1H NMR spectra changes at various pD values in D2O suggest that strong intramolecular hydrogen bonds link each adjacent Zn(II)-OH2 (or Zn(II)-OH-) at neutral pH in aqueous solution. At higher pH (> 9), the hydrogen bond network disrupts. The 31P NMR titration of Zn3L3.3H2O with phenyl phosphate dianion (PP2-) in D2O confirmed the formation of a 1:1 complex (Zn3L3-PP2-). By potentiometric pH titrations, the 1:1 complex affinity constants, log K(aff) (K(aff) = [phosphate complex]/[Zn(II) complex] [phosphate] (M-1)), were determined to be 5.8 with NPP2-, 6.6 with PP2-, 7.0 with α-D-glucose-1-phosphate, and 7.9 with phenyl phosphonate in aqueous solution. The tris(Zn(II)-cyclen) complex is found to be a much better host toward phosphates than the parent Zn(II)-cyclen (ZnL1) (log K(aff) = 3.3 for ZnL1-NPP2-) or a bis(Zn(II)-cyclen) linked with a m-xylene spacer (Zn2L2) (log K(aff) = 4.0 for Zn2L2-NPP2-).

Dibridged bis(Zn2+-cyclen): A novel host molecule of malonate dianion in aqueous solution

A dinuclear zinc(II) complex, m,m-bis(Zn2+cyclen) was synthesized as a novel host molecule for a malonate dianion. The dizinc(II) complex has two zinc(II)cyclen moieties (cyclen = 1,4,7,10- tetraazacyclododecane) connected through two m-xylene bridges. The 1:1 association constant of log K (K = {[malonate-bound m,m-bis(Zn 2+-cyclen)]/[m,m-bis(Zn2+-cyclen)][malonate]}/M -1) was determined to be 3.6 by potentiometric pH titration at 25°C with I = 0.10M (NaNO3) in aqueous solution. The H/D exchange reaction of methylene hydrogen atoms of malonate dianion was accelerated by m,m-bis(Zn2+-cyclen) in D2O. The half-life was determined to be 80min for a 1:1 mixture (2mM) of malonate and m,m-bis(Zn 2+-cyclen) at 25°C and pD 7. From an aqueous solution of equimolar malonate and m,m-bis(Zn2+-cyclen) however, a cyclic 2:2 malonate/m,m-bis(Zn2+-cyclen) complex was isolated. The structure was confirmed by X-ray crystallography.

Linked cyclic polyamines with activity against hiv.

There is disclosed a pharmaceutical composition comprising as active ingredient a linked cyclic compound of general formula I,Z - R - A - R' - Y in which Z and Y are independently cyclic polyamine moieties having from 9 to 32 ring members and from 3 to 8 amine nitrogens in the ring spaced by 2 or more carbon atoms from each other, ???A is an aromatic or heteroaromatic moiety, ???R and R' are each a substituted or unsubstituted alkylene chain or heteroatom containing chain. or an acid addition salt or metal complex thereof, in admixture or association with a pharmaceutically acceptable diluent or carrier.

Bis-aminals: Efficient tools for bis-macrocycle synthesis

Tetraazamacrocyclic bis-aminals prove to be excellent tools for the synthesis of symmetrical, dissymmetrical or functionalized bis-tetraazamacrocycles. The key feature of the process is the separation of insoluble mono- or bis-quaternary ammonium salts from solution during the course of the alkylation reaction.

Expeditious N-monoalkylation of 1,4,7,10-tetraazacyclododecane (cyclen) via formamido protection

The reaction of cyclen 1 with chloral hydrate afforded exclusively 1,4,7-triformylcyclen 2 in high yield; the triprotected macrocycle was easily alkylated with various electrophiles in good to excellent yields. The alkaline removal of the formyl groups pr

New facile and convenient synthesis of bispolyazamacrocycles using Boc protection. Determination of geometric parameters of dinuclear copper(II) complexes using ESR spectroscopy and molecular mechanics calculations

A new facile and convenient synthetic route has been designed for the preparation of bispolyazamacrocycles in high yields by direct condensation of the readily available intermediate //,W-diboctriazamacrocycle or N,N',N"triboctetraazamacrocycles with aromatic biselectrophiles, ie, o-, m-, p-xylyl and anthracenyl derivatives. The use of a versatile group, such as ferf-butyloxycarbonyl (Boc), which is easily removed within l h by treatment with 6 M HC1 or TFA, leads to polyazamacrocycles in which one nitrogen is discriminated from the others. The anthracenyl and o-xylyl dimers were synthesized by reacting diacyl chloride to give the corresponding diamides. Further reduction of the amide groups and elimination of the protecting Boc moieties were carried in a one-pot reaction with BHa-THF followed by acid treatment. In parallel, exclusive mono-JV-alkylation of the available secondary amine of the same protected macrocycle with the corresponding dibromoxylene gave the meta and para dimers; the protecting moieties were eliminated in a similar way. ESR measurements of spin-spin distances of the dicopper complexes were determined from the ratio of the intensity of the forbidden transition to the intensity of the allowed transitions. Molecular mechanics calculations were also undertaken in order to evaluate the Cu-Cu distance by using a new rule-based force field. Eisevier,.

Synthesis and structure-activity relationships of phenylenebis(methylene)- linked bis-tetraazamacrocycles that inhibit HIV replication. Effects of macrocyclic ring size and substituents on the aromatic linker

We have previously described the potent and selective inhibition of several strains of human immunodeficiency virus type 1 (HIV-1) and type 2 (HIV-2) by JM2763, an n-propyl-linked dimer of the 1,4,8,11- tetraazamacrocyclic(cyclam) ring system. Upon further investigation, we have also found that incorporating an aromatic rather than aliphatic linker leads to analogs with higher antiviral potency. The prototype, JM3100 (19a, isolated as the octahydrochloride salt), which contains a p- phenylenebis(methylene) moiety linking the cyclam rings, inhibited the replication of HIV-1 (III(B)) and HIV-2 (ROD) at EC50's of 4.2 and 5.9 nM, respectively, while remaining nontoxic to MT-4 cells at concentrations exceeding 421 μM. In order to identify the structural features of bis- tetraazamacrocycles required for potent activity, we have prepared a novel series of phenylenebis(methylene)-linked analogs, in which the macrocyclic ring size was varied from 12 to 16 ring members. Depending upon the substitution of the phenylenebis-(methylene) linker (para or meta), sub- micromolar anti-HIV activity was exhibited by analogs bearing macrocycles of 12-14 ring members but with varying cytotoxicity to MT-4 cells. Furthermore, while we found that identical macrocyclic rings are not required for activity, substituting an acyclic polyamine equivalent for one of the cyclam rings in 19a resulted in a substantial reduction in anti-HIV potency, clearly establishing the importance of the constrained macrocyclic structure. A short series of transition metal complexes of 19a were also prepared and evaluated. Complexes of low kinetic stability such as the bis-zinc complex retained activity comparable to that of the parent compound. Finally, the activity of bicyclam analogs appears to be insensitive to the electron-withdrawing or - donating properties of substituents introduced onto the linker, but sterically hindering groups such as phenyl markedly reduced activity. As a result, several analogs with anti-HIV potency comparable to that of 19a have been identified.

Mono N-Functionalization of Cyclic and Linear Tetraamines via Their Tridentate Tricarbonylchromium Complexes

The fac-LCr(CO)3 tridentate complexes of 1,4,7,10-tetraazacyclododecane 1, 1,4,8,11-tetraazacyclotetradecane 2, 1,4,7,10-tetraazadecane 3 and 1,5,8,12-tetraazadodecane 4 have been shown selectively alkylated in high yield at the uncomplexed nitrogen atom, giving rise to mono N-functionalized tetraamines and bis-macrocyclic compounds.