60239-18-1

Basic information

• Product Name: DOTA
• Synonyms: 1,4,7,10-TETRAAZACYCLODODECANE-1,4,7,10-TETRAACETIC ACID;1,4,7,10-TETRAAZACYCLODODECANE-1,4,7,10-TETRAACETIC ACID, FREE ACID;1,4,7,10-TETRAAZACYCLODODECANE-N,N',N'',N'''-TETRAACETIC ACID;DOTA;TETRAAZA-12-CROWN-4-1,4,7,10-TETRAACETIC ACID;NSC 681107;TETRAXETAN;1,4,7,10-Tetraazacyclododecane-N,N',N'',N'''-tetraaceticacid,min.98%DOTA
• CAS NO: 60239-18-1
• Molecular Formula: C₁₆H₂₈N₄O₈
• Molecular Weight: 404.42
• EINECS: 1592732-453-0
• Product Categories: Azacrown Ethers;Functional Materials;Macrocycles for Host-Guest Chemistry;Achiral Nitrogen;Cy-N
• Mol File: 60239-18-1.mol
• Article Data: 30

Chemical Properties

• Melting Point: 267 °C
• Boiling Point: 701.6 °C at 760 mmHg
• Flash Point: 378.1 °C
• Appearance: white/Powder
• Density: 1.321
• Vapor Pressure: 1.51E-21mmHg at 25°C
• Refractive Index: 1.531
• Storage Temp.: Sealed in dry,Room Temperature
• Solubility: Water (Slightly, Heated), Methanol (Slightly)
• PKA: 2.16±0.10(Predicted)
• Stability: Hygroscopic
• BRN: 1186987
• CAS DataBase Reference: DOTA(CAS DataBase Reference)
• NIST Chemistry Reference: DOTA(60239-18-1)
• EPA Substance Registry System: DOTA(60239-18-1)

Safety Data

• Hazard Codes: Xi
• Statements: 36/37/38
• Safety Statements: 26-36
• WGK Germany: 3
• F: 3-10-34
• Hazardous Substances Data: 60239-18-1(Hazardous Substances Data)

Usage

Chemical Properties

Colourless crystals

Uses

Different sources of media describe the Uses of 60239-18-1 differently. You can refer to the following data:
1. Bifunctional DOTA aconjugates to peptides and has become an established strategy for constructing target-specific metal containing agents including targeted MRI contrast agents and diagnostic and ther apeutic radiopharmaceuticals.
2. 1,4,7,10-Tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) is a macrocyclic complexing agent.It has been used for radiolabeling of carbon nanotube bioconjugates by chelating 64Cu radioisotope.DOTA can be activated with N-hydroxysulfosuccinimidyl for conjugation with monoclonal antibodies in clinical radioimmunotherapy.It can form complexes with gadolinium for application as MRI contrast agents.Metal complexes of DOTA-peptide conjugates can be used as therapeutic radiopharmaceuticals.

Definition

ChEBI: An azamacrocyle in which four nitrogen atoms at positions 1, 4, 7 and 10 of a twelve-membered ring are each substituted with a carboxymethyl group.

InChI:InChI=1/C16H28N4O8/c21-13(22)9-17-1-2-18(10-14(23)24)5-6-20(12-16(27)28)8-7-19(4-3-17)11-15(25)26/h1-12H2,(H,21,22)(H,23,24)(H,25,26)(H,27,28)

Synthetic route

1,4,7-tris(tert-butoxycarbonylmethyl)-1,4,7,10-tetraazacyclododecane-10-acetic acid (137076-54-1) → 1,4,7,10-tetrakis(carboxymethyl)-1,4,7,10-tetraazacyclododecane (60239-18-1) + tert-butyl alcohol (75-65-0)

Conditions	Yield
With chlorotriisopropylsilane; water; trifluoroacetic acid for 3h; Time; Reagent/catalyst; Solvent;	A 100% B 100%

C43H58N4O8 (1412494-57-5) → 1,4,7,10-tetrakis(carboxymethyl)-1,4,7,10-tetraazacyclododecane (60239-18-1) + 1-methyl-1-phenylethyl alcohol (617-94-7)

Conditions	Yield
With chlorotriisopropylsilane; water; trifluoroacetic acid for 0.833333h; Time; Reagent/catalyst; Solvent;	A 100% B 100%

2-(4,7,10-tris(2-(tert-butoxy)-2-oxoethyl)-1,4,7,10-tetraazacyclododecan-1-yl)acetic acid → 1,4,7,10-tetrakis(carboxymethyl)-1,4,7,10-tetraazacyclododecane (60239-18-1)

Conditions	Yield
With trifluoroacetic acid In dichloromethane for 12h;	89%
With trifluoroacetic acid In dichloromethane at 20℃; for 16h;	85%
With trifluoroacetic acid In dichloromethane at 20℃;

chloroacetic acid (79-11-8) + 1,4,7,10-tetraazacyclododecan (294-90-6) → 1,4,7,10-tetrakis(carboxymethyl)-1,4,7,10-tetraazacyclododecane (60239-18-1)

Conditions	Yield
With sodium hydroxide In water at 70℃; for 30h; pH=9.5 - 10;	88%
With (-)-cycleanine; sodium hydroxide In water at 80 - 85℃; pH=10 - 11; Large scale;	82.7%
With sodium hydroxide In water at 80 - 85℃; pH=10 - 11; Industrial scale;	82.7%

bromoacetic acid (79-08-3) + 1,4,7,10-tetraazacyclododecan (294-90-6) → 1,4,7,10-tetrakis(carboxymethyl)-1,4,7,10-tetraazacyclododecane (60239-18-1)

Conditions	Yield
With lithium hydroxide monohydrate; water at 0 - 30℃; for 24h; Temperature; Reagent/catalyst;	87.8%

tetraethyl 2,2',2'',2'''-(1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrayl)tetraacetate → 1,4,7,10-tetrakis(carboxymethyl)-1,4,7,10-tetraazacyclododecane (60239-18-1)

Conditions	Yield
With water; sodium hydroxide In methanol at 55 - 60℃; for 12h;	80.5%

Iodoacetic acid (64-69-7) + 1,4,7,10-tetraazacyclododecan (294-90-6) → 1,4,7,10-tetrakis(carboxymethyl)-1,4,7,10-tetraazacyclododecane (60239-18-1)

Conditions	Yield
With lithium hydroxide monohydrate; water at 0 - 30℃; for 24h;	72%

chloroacetic acid lithium salt (19326-51-3) + 1,4,7,10-tetraazacyclododecan (294-90-6) → 1,4,7,10-tetrakis(carboxymethyl)-1,4,7,10-tetraazacyclododecane (60239-18-1)

Conditions	Yield
With lithium hydroxide monohydrate; water at 0 - 30℃; for 24h;	43.8%

bromoacetic acid methyl ester (96-32-2) + 1,4,7,10-tetraazacyclododecan (294-90-6) → 1,4,7,10-tetrakis(carboxymethyl)-1,4,7,10-tetraazacyclododecane (60239-18-1)

Conditions	Yield
With lithium hydroxide monohydrate; water at 0 - 30℃; for 24h;	32.5%

ethyl bromoacetate (105-36-2) + 1,4,7,10-tetraazacyclododecan (294-90-6) → 1,4,7,10-tetrakis(carboxymethyl)-1,4,7,10-tetraazacyclododecane (60239-18-1)

Conditions	Yield
With lithium hydroxide monohydrate; water at 0 - 30℃; for 24h;	24.8%

1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid mono(4-nitrophenyl) ester (474424-15-2) → 1,4,7,10-tetrakis(carboxymethyl)-1,4,7,10-tetraazacyclododecane (60239-18-1) + 4-nitro-phenol (100-02-7)

Conditions	Yield
In water for 1h; pH=7; Kinetics; Further Variations:; pH-values;

N,N',N'',N'''-tetrakis-(p-tolylsulphonyl)-triethylenetetramine (55442-07-4) → 1,4,7,10-tetrakis(carboxymethyl)-1,4,7,10-tetraazacyclododecane (60239-18-1)

Conditions	Yield
Multi-step reaction with 3 steps 1: 78 percent / K2CO3 / dimethylformamide / 30 h / 100 °C 2: 33 percent / conc. H2SO4 / 28 h / 115 °C 3: 88 percent / NaOH / H2O / 30 h / 70 °C / pH 9.5 - 10 View Scheme

cyclen tetratosylate (52667-88-6) → 1,4,7,10-tetrakis(carboxymethyl)-1,4,7,10-tetraazacyclododecane (60239-18-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: 33 percent / conc. H2SO4 / 28 h / 115 °C 2: 88 percent / NaOH / H2O / 30 h / 70 °C / pH 9.5 - 10 View Scheme

triethylentetramine (112-24-3) → 1,4,7,10-tetrakis(carboxymethyl)-1,4,7,10-tetraazacyclododecane (60239-18-1)

Conditions	Yield
Multi-step reaction with 4 steps 1: 97 percent / Et3N / acetonitrile / 5 h / 20 °C 2: 78 percent / K2CO3 / dimethylformamide / 30 h / 100 °C 3: 33 percent / conc. H2SO4 / 28 h / 115 °C 4: 88 percent / NaOH / H2O / 30 h / 70 °C / pH 9.5 - 10 View Scheme

2Na(1+)*Pb(2+)*(N(CH2COO)C2H4)4(4-)*2H2O=Na2Pb(N(CH2COO)C2H4)4*2H2O → 1,4,7,10-tetrakis(carboxymethyl)-1,4,7,10-tetraazacyclododecane (60239-18-1) + lead(2+) cation

Conditions	Yield
In perchloric acid Kinetics; decompn. of Pb compd. in aq. HClO4 depending from acid concn.;

C46H62N4O8 (1412494-56-4) → 1,4,7,10-tetrakis(carboxymethyl)-1,4,7,10-tetraazacyclododecane (60239-18-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: tetrakis(triphenylphosphine) palladium(0); 4-methyl-morpholine / dichloromethane / 3 h / 20 °C 2: chlorotriisopropylsilane; trifluoroacetic acid; water / 0.83 h View Scheme

(1,4,7,10-tetraaza-cyclododec-1-yl)-acetic acid allyl ester (1023970-58-2) → 1,4,7,10-tetrakis(carboxymethyl)-1,4,7,10-tetraazacyclododecane (60239-18-1)

Conditions	Yield
Multi-step reaction with 3 steps 1: potassium carbonate / acetonitrile / 16 h / 20 °C 2: tetrakis(triphenylphosphine) palladium(0); 4-methyl-morpholine / dichloromethane / 2 h / 20 °C 3: chlorotriisopropylsilane; trifluoroacetic acid; water / 3 h View Scheme
Multi-step reaction with 3 steps 1: potassium carbonate / acetonitrile / 8 h / 20 °C 2: tetrakis(triphenylphosphine) palladium(0); 4-methyl-morpholine / dichloromethane / 3 h / 20 °C 3: chlorotriisopropylsilane; trifluoroacetic acid; water / 0.83 h View Scheme

C31H56N4O8 (1412494-55-3) → 1,4,7,10-tetrakis(carboxymethyl)-1,4,7,10-tetraazacyclododecane (60239-18-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: tetrakis(triphenylphosphine) palladium(0); 4-methyl-morpholine / dichloromethane / 2 h / 20 °C 2: chlorotriisopropylsilane; trifluoroacetic acid; water / 3 h View Scheme

1,4,7,10-tetraazacyclododecan (294-90-6) → 1,4,7,10-tetrakis(carboxymethyl)-1,4,7,10-tetraazacyclododecane (60239-18-1)

Conditions	Yield
Multi-step reaction with 2 steps 1: potassium carbonate / chloroform / 52 h / 20 °C 2: trifluoroacetic acid / dichloromethane / 12 h View Scheme
Multi-step reaction with 2 steps 1: potassium carbonate / acetonitrile / 40 h / Reflux 2: sodium hydroxide; water / methanol / 12 h / 55 - 60 °C View Scheme
Multi-step reaction with 2 steps 1: chloroform / 72 h / 20 °C 2: trifluoroacetic acid / dichloromethane / 20 °C View Scheme

cyclen hydrochloride + chloroacetic acid (79-11-8) → 1,4,7,10-tetrakis(carboxymethyl)-1,4,7,10-tetraazacyclododecane (60239-18-1)

Conditions	Yield
With sodium hydroxide In water at 0 - 75℃; pH=10 - 10.5;
Stage #1: cyclen hydrochloride; chloroacetic acid With hydrogenchloride; sodium hydroxide In water at 0 - 75℃; pH=10 - 10.5; Stage #2: In water pH=2.5 - 3;
With sodium hydroxide In water at 10 - 30℃; for 24h; Reagent/catalyst;

sodium monochloroacetic acid (3926-62-3) + 1,4,7,10-tetraazacyclododecan (294-90-6) → 1,4,7,10-tetrakis(carboxymethyl)-1,4,7,10-tetraazacyclododecane (60239-18-1)

Conditions	Yield
With sodium hydroxide In water for 5h; pH=11; Concentration; Large scale;
With lithium hydroxide monohydrate; water at 0 - 30℃; for 24h;

sodium 2-bromoacetate (1068-52-6) + 1,4,7,10-tetraazacyclododecan (294-90-6) → 1,4,7,10-tetrakis(carboxymethyl)-1,4,7,10-tetraazacyclododecane (60239-18-1)

Conditions	Yield
With lithium hydroxide monohydrate; water at 0 - 30℃; for 24h;

potassium iodoacetate (15973-59-8) + 1,4,7,10-tetraazacyclododecan (294-90-6) → 1,4,7,10-tetrakis(carboxymethyl)-1,4,7,10-tetraazacyclododecane (60239-18-1)

Conditions	Yield
With lithium hydroxide monohydrate; water at 0 - 30℃; for 24h;

monosodium iodoacetate (305-53-3) + 1,4,7,10-tetraazacyclododecan (294-90-6) → 1,4,7,10-tetrakis(carboxymethyl)-1,4,7,10-tetraazacyclododecane (60239-18-1)

Conditions	Yield
With lithium hydroxide monohydrate; water at 0 - 30℃; for 24h;

1,4,7,10-tetrakis(carboxymethyl)-1,4,7,10-tetraazacyclododecane (60239-18-1) + gadolinium(III) chloride hexahydrate → gadoteric acid (72573-82-1)

Conditions	Yield
With potassium hydroxide In water at 60℃; for 24h; pH=5.5 - 7;	100%

1,4,7,10-tetrakis(carboxymethyl)-1,4,7,10-tetraazacyclododecane (60239-18-1) + manganese (II) sulfate monohydrate → Mn(1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid(2-))*2H2O

Conditions	Yield
In water MnSO4*H2O dissolved in H2O, ligand added, stirred for 30 min; H2O evapd.; elem. anal.;	99%

1,4,7,10-tetrakis(carboxymethyl)-1,4,7,10-tetraazacyclododecane (60239-18-1) + scandium(III) acetate (3804-23-7) + sodium hydroxide (1310-73-2) → 3(Na[Sc(1,4,7,10-tetra-azacyclododecane-N,N',N'',N'''-tetraacetate)])*NaOH*18H2O

Conditions	Yield
In water to aq. suspn. H4DOTA NaOH was added until pH 5, Sc(acetate)3 was added and heated at 60°C for 12 h at pH 4; soln. was concd., residue was dissolved in water, basified with NaOH at pH 7.0 and evapd. to dryness under reduced pressure;	95%

lanthanum(III) oxide + 1,4,7,10-tetrakis(carboxymethyl)-1,4,7,10-tetraazacyclododecane (60239-18-1) + sodium hydroxide (1310-73-2) → Na(1+)*2La(3+)*C8H16N4(CH2CO2)4(4-)*C8H16N4(CH2CO2)3CH2CO2H(3-)*10H2O=Na[La2(C8H16N4(CH2CO2)4)2H]*10H2O

Conditions	Yield
In water stoich. amts., 85°C, stirring for several d; cooling to room temp., filtration, evapn. (reduced pressure);	93%

gadolinium(III) oxide + 1,4,7,10-tetrakis(carboxymethyl)-1,4,7,10-tetraazacyclododecane (60239-18-1) + 1-deoxy-1-(methylamino)-D-glucitol (6284-40-8) → gadoterate meglumine

Conditions	Yield
Stage #1: 1,4,7,10-tetrakis(carboxymethyl)-1,4,7,10-tetraazacyclododecane; 1-deoxy-1-(methylamino)-D-glucitol In water for 0.05h; Green chemistry; Stage #2: gadolinium(III) oxide In water for 0.283333h; Sonication; Green chemistry;	89%

morpholine (110-91-8) + gadolinium(III) oxide + 1,4,7,10-tetrakis(carboxymethyl)-1,4,7,10-tetraazacyclododecane (60239-18-1) → gadoterate morpholine

Conditions	Yield
Stage #1: morpholine; 1,4,7,10-tetrakis(carboxymethyl)-1,4,7,10-tetraazacyclododecane In water for 0.05h; Sonication; Green chemistry; Stage #2: gadolinium(III) oxide In water for 0.283333h; Sonication; Green chemistry;	85%

gadolinium(III) oxide + 1,4,7,10-tetrakis(carboxymethyl)-1,4,7,10-tetraazacyclododecane (60239-18-1) → Na(1+)*Gd(3+)*(CH2CH2N(CH2COO))4(4-)*H2O*4H2O=Na{Gd(CH2CH2N(CH2COO))4H2O}*4H2O

Conditions	Yield
In water Gd2O3 and tetraazacyclododecanetetraacetic acid soln. was stirred at 368 K for 2 h, NaOH was slowly added at room temp. to pH 7 with stirring; after filtration mixt. was concd. in vac. and pptd. with acetone; recrystn. from hot H2O/acetone; elem. anal.;	83%

gadolinium(III) oxide + 1,4,7,10-tetrakis(carboxymethyl)-1,4,7,10-tetraazacyclododecane (60239-18-1) + 1-deoxy-1-(methylamino)-D-glucitol (6284-40-8) → gadoteric dcid meglumine

Conditions	Yield
In water at 40 - 50℃; for 3h; pH=7 - 9; Industrial scale;	82%

1,4,7,10-tetrakis(carboxymethyl)-1,4,7,10-tetraazacyclododecane (60239-18-1) + nickel(II) → {(CH2CH2)NCH2COOH}2{(CH2CH2)NCH2COO}2Ni (107171-59-5)

Conditions	Yield
In water equimolar amounts of ligand and metal salt; pH 2.5;; crystallization after several days; elem. anal.;;	80%

gadolinium(III) oxide + 1,4,7,10-tetrakis(carboxymethyl)-1,4,7,10-tetraazacyclododecane (60239-18-1) + (2S,3S,4S,5R)-6-(methylamino)hexane-1,2,3,4,5-pentaol → gadoteric dcid meglumine

Conditions	Yield
In water at 40 - 50℃; for 3h; pH=7 - 9; Large scale;	78.5%

1,4,7,10-tetrakis(carboxymethyl)-1,4,7,10-tetraazacyclododecane (60239-18-1) + p-xylylidenediamine (539-48-0) → 2,2',2''-(10-(2-(4-(aminomethyl)benzylamino)-2-oxoethyl)-1,4,7,10-tetraazacyclo-dodecane-1,4,7-triyl)triacetic acid (1314043-15-6)

Conditions	Yield
With pyridine; diisopropyl-carbodiimide In water; acetonitrile	75%

1,4,7,10-tetrakis(carboxymethyl)-1,4,7,10-tetraazacyclododecane (60239-18-1) + zinc(II) cation → (1,4,7,10-tetraazacyclododecane-N,N',N''-N'''-dihydrogentetraacetato)zinc (107171-57-3, 277333-19-4)

Conditions	Yield
In water equimolar amounts of ligand and metal salt; pH 2.5;; crystallization after several days; elem. anal.;;	72%

1,4,7,10-tetrakis(carboxymethyl)-1,4,7,10-tetraazacyclododecane (60239-18-1) + 2-AMINOETHYL TRIMETHYLAMMONIUM CHLORIDE (10256-43-6) → 10-<2-(trimethylammonio)ethylcarbamoylmetyhyl>-1,4,7,10-tetraazacyclododecane-1,4,7-tri(triacetic acid) chloride

Conditions	Yield
With dicyclohexyl-carbodiimide In pyridine; acetonitrile at 20℃; for 48h;	71%

1,4,7,10-tetrakis(carboxymethyl)-1,4,7,10-tetraazacyclododecane (60239-18-1) + copper(II) ion → {(CH2CH2)NCH2COOH}2{(CH2CH2)NCH2COO}2Cu (107171-58-4, 277333-30-9)

Conditions	Yield
In water equimolar amounts of ligand and metal salt; pH 2.5;; crystallization after several days; elem. anal.;;	69%

gadolinium(III) oxide + 1,4,7,10-tetrakis(carboxymethyl)-1,4,7,10-tetraazacyclododecane (60239-18-1) → gadolinium(III) 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (72573-82-1)

Conditions	Yield
In water for 3h;	67.9%
In water addn. of gadolinium oxide to aq. soln. of tetraazacyclododecane deriv., mixt. heated at 90°C for 12 h; cooling to room temp., addn. of cation-exchange and anion-exchange resins, stirring for 60 min at room temp., filtration, filtrate freeze dried;	61%

1,4,7,10-tetrakis(carboxymethyl)-1,4,7,10-tetraazacyclododecane (60239-18-1) + NO2(C6H4)CH2CH(C(O)NHCH2CH2NH2)NHC(O)(C6H4)((C9BN2)(F)2(CH3)4(CH2CH3)2) → NO2(C6H4)CH2CH(C(O)NHCH2CH2NHC(O)CH2(C8H16N4)(CH2C(O)OH)3)NHC(O)(C6H4)((C9BN2)(F)2(CH3)4(CH2CH3)2)

Conditions	Yield
With triethylamine In N,N-dimethyl-formamide at 20℃; for 12h;	65%

1,4,7,10-tetrakis(carboxymethyl)-1,4,7,10-tetraazacyclododecane (60239-18-1) + 3-bromopropyl biotin (1296869-99-2) → C29H48N6O11S

Conditions	Yield
With 1,8-diazabicyclo[5.4.0]undec-7-ene In acetonitrile at 82℃; for 18h;	65%

1,4,7,10-tetrakis(carboxymethyl)-1,4,7,10-tetraazacyclododecane (60239-18-1) + 3-amino-deoxycombretastatin A4 (162705-07-9) → C34H47N5O11

Conditions	Yield
Stage #1: 1,4,7,10-tetrakis(carboxymethyl)-1,4,7,10-tetraazacyclododecane With thionyl chloride for 4h; Reflux; Stage #2: 3-amino-deoxycombretastatin A4 With N-ethyl-N,N-diisopropylamine In dichloromethane at 30℃; for 3h; Cooling with ice;	65%

1,4,7,10-tetrakis(carboxymethyl)-1,4,7,10-tetraazacyclododecane (60239-18-1) + N,N-bis(ethoxycarbonylmethyl)ethylenediamine → (Ethoxycarbonylmethyl-{2-[2-(4,7,10-tris-{[2-(bis-ethoxycarbonylmethyl-amino)-ethylcarbamoyl]-methyl}-1,4,7,10-tetraaza-cyclododec-1-yl)-acetylamino]-ethyl}-amino)-acetic acid ethyl ester

Conditions	Yield
With (benzotriazo-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate; triethylamine In chloroform; N,N-dimethyl-formamide at 20℃; for 30h;	63%

1,4,7,10-tetrakis(carboxymethyl)-1,4,7,10-tetraazacyclododecane (60239-18-1) + copper(ll) sulfate pentahydrate → {(CH2CH2)NCH2COO}4(4-)*2Cu(2+)*5H2O={(CH2CH2)NCH2COO}4Cu2*5H2O

Conditions	Yield
In water pH=4; stochiometric amounts;; after 2-3 days crystallization; elem. anal.;;	60%

1,4,7,10-tetrakis(carboxymethyl)-1,4,7,10-tetraazacyclododecane (60239-18-1) + Met-OMe (10332-17-9) → C40H72N8O12S4

Conditions	Yield
With O-(1H-benzotriazol-1-yl)-N,N,N',N'-tetramethyluronium hexafluorophosphate; N-ethyl-N,N-diisopropylamine In N,N-dimethyl-formamide at 20℃; for 24h;	55%

1,4,7,10-tetrakis(carboxymethyl)-1,4,7,10-tetraazacyclododecane (60239-18-1) + gadolinium(III) trifluoromethanesulfonate → gadolinium 2-[4,7,10-tris(carboxymethyl)-1,4,7,10-tetraazacyclododec-1-yl]acetic acid (783303-01-5, 83678-67-5, 881694-36-6, 881694-49-1)

Conditions	Yield
With triethylamine In methanol at 45℃; for 48h;	55%

Upstream product

• 79-11-8 chloroacetic acid 
• 294-90-6 1,4,7,10-tetraazacyclododecan 
• 19326-51-3 chloroacetic acid lithium salt 
• 96-32-2 bromoacetic acid methyl ester 
• 105-36-2 ethyl bromoacetate 
• 305-53-3 monosodium iodoacetate 
• 15973-59-8 potassium iodoacetate 
• 1068-52-6 sodium 2-bromoacetate 
• 64-69-7 Iodoacetic acid 
• 79-08-3 bromoacetic acid 
• 137076-50-7 tetraethyl 2,2',2'',2'''-(1,4,7,10-tetraazacyclododecane-1,4,7,10-tetrayl)tetraacetate 
• 3926-62-3 sodium monochloroacetic acid 
• 1412494-55-3 C₃₁H₅₆N₄O₈ 
• 1023970-58-2 (1,4,7,10-tetraaza-cyclododec-1-yl)-acetic acid allyl ester 

Downstream Products

• 72573-82-1 gadolinium(III) 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid 
• 92943-93-6 gadoterate meglumine 
• 72573-82-1 gadoteric acid 

Relevant articles and documents

Cherenkov Radiation-Mediated In Situ Excitation of Discrete Luminescent Lanthanide Complexes

Lanthanide luminescence, while ideal for in vivo applications owing to sharp emission bands within the optical window, requires high-intensity, short-wavelength excitation of small organic “antenna” chromophores in the vicinity of the lanthanide complex to access excited f-orbital states through intersystem crossing. Herein, we explored Cherenkov radiation of the radioisotopes 18F and 89Zr as an in situ source of antenna excitation. The effective inter- and intramolecular excitation of the terbium(III) complexes of a macrocylic polyaminocarboxylate ligand (hydration number (q)=0, quantum yield (φ)=47 %) as well as its analogue functionalized to append an intramolecular Cherenkov excitation source (q=0.07, φ=63 %) was achieved. Using conventional small-animal fluorescence imaging equipment, we have determined a detection limit of 2.5 nmol of Tb(III) complex in presence of 10 μCi of 18F or 89Zr. Our system is the first demonstration of the optical imaging of discrete luminescent lanthanide complexes without external short-wave excitation.

METHOD FOR PREPARING 1,4,7,10-TETRAAZACYCLODODECANE-1,4,7,10-TETRAACETIC ACID

Disclosed is a method for preparing 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid (DOTA) of formula (II), comprising the following steps: carrying out an alkylation reaction on cyclen in formula (I) and XCH2COOR in the presence of an acid-binding agent in water; adjusting a pH value to separate out a crude product of DOTA; and recrystallizing. The preparation method of the present invention is applicable to large-scale industrial production of DOTA, the whole process does not need to adopt an ion-exchange resin or low-temperature refrigeration mode for purification, and the purity and yield of the product are higher.

General Approach to Direct Measurement of the Hydration State of Coordination Complexes in the Gas Phase: Variable Temperature Mass Spectrometry

The formation of ternary aqua complexes of metal-based diagnostics and therapeutics is closely correlated to their in vivo efficacy but approaches to quantify the presence of coordinated water ligands are limited. We introduce a general and high-throughput method for characterizing the hydration state of para- and diamagnetic coordination complexes in the gas phase based on variable-temperature ion trap tandem mass spectrometry. Ternary aqua complexes are directly observed in the mass spectrum and quantified as a function of ion trap temperature. We recover expected periodic trends for hydration across the lanthanides and distinguish complexes with several inner-sphere water ligands by inspection of temperature-dependent speciation curves. We derive gas-phase thermodynamic parameters for discernible inner- and second-sphere hydration events, and discuss their application to predict solution-phase behavior. The differences in temperature at which water binds in the inner and outer spheres arise primarily from entropic effects. The broad applicability of this method allows us to estimate the hydration states of Ga, Sc, and Zr complexes under active preclinical and clinical study with as-yet undetermined hydration number. Variable-temperature mass spectrometry emerges as a general tool to characterize and quantitate trends in inner-sphere hydration across the periodic table.