Patent Application: US-14296008-A

Abstract:
the scheme illustrates the synthesis mechanism of the new materials . this invention involves the combination of gelatine with organic salts in the solid or liquid state . for that purpose , gelatines of several origins can be used . wherein x ⊖ represents the anion of the salt and y ⊕ represents the cation of the salt . the invention relates also to the application of said synthesized new materials in the domains of physics , chemistry and biology , disclosing the process for the synthesis of the new materials and the use thereof as supports for biocatalysts immobilization in chemical reactions , controlled drug delivery , manufacturing of sensors / biosensors aimed at the detection of chemical species , manufacturing of conductive / semi - conductive materials , electrochemical cells or parts of cells .

Description:
embodiments of the present invention differ from baroli et al . because in the process of embodiments of the present invention for the manufacturing of the material there is no polymerization being employed , since the material results from the cross - linking of the two species . this invention relates to the synthesis and application of a family of new materials resulting from the cross - linking of both species . the present invention comprises the synthesis and application of a family of new materials resulting from the cross - linking between proteins and organic salts . the scheme ( i ) illustrates the synthesis mechanism of said new materials wherein x ⊖ represents the anion of the salt and y ⊕ represents the cation of the salt , and wherein gelatines of several origins ( animal , microbial , vegetal ) can be used , in association with different types of organic salts . a common procedure for obtaining this type of material is the following : to a salt solution is added a portion of gelatine under stirring , in order to yield solid , homogeneous and elastic gelatine . the amount of gelatine to be added is related to the characteristics of the salt solutions to be used in each case . therefore , the amount of added gelatine will depend on the type of organic salt used , and consequently on its water solubility . the salt used shall be dissolved in water . its concentration shall be in the range from 4 to 50 % ( w / v ), this depending on the water solubility of the salt . at this point , the gelatine is to be incorporated in the system until an elastic and solid phase is obtained . the addition of gelatine shall be made gradually , in order to ensure that the mixture remains homogeneous between each of the additions of gelatine . in certain cases , water must be added to the system in order to provide a better homogenization of all the phases , as well as to allow for an improved interaction between the gelatine and the salt . during this process , parameters such as the temperature , ionic strength and ph shall be monitored . the temperature is a parameter which must be controlled during the whole process . this affects the solubility of gelatine in the salt solution , as well as the cross - linking . the process is faster at a temperature from 60 to 90 ° c ., but it will work from 20 to 90 ° c . the ionic strength is directly associated with the degree of cross - linking between the gelatine and the salt . therefore , the ionic strength depends both on the amount of gelatine , and on the type of salt used for manufacturing the material . in a typical process , the salt / gelatine ratio will vary from 0 . 5 to 10 , and the corresponding ionic strength will vary from 1 m to 60 m . the type of salt can have an influence on the ph of the mixture , and so it is vital to check the ph of the solution prior to manufacturing the material . the material can be produced at any ph value , but the manufacturing process works better if it is within the range from 5 to 9 . another aspect to be considered is the stirring of the mixture . this stirring shall make all the phases to be adequately homogenized . several types of stirring ( orbital , magnetic , mechanical ) were assayed . all of them gave very satisfactory results . the final form of the material is determined by the surface where the gelification occurs . so , one can obtain thin films , compact blocks , or particles in case there is a dispersion of the material formed . the physical properties of the materials , such as colour and opacity , elasticity and conductivity , depend on the type of ionic liquid used and on the final form of the material . thus , the first object of the invention is the synthesis of new materials based on gelatine and organic salts , characterized in that the cross - linking of between the gelatine unit and the organic salts ( i ) wherein x ⊖ represents the anion of the salt and y ⊕ represents the cation of the salt , is carried out in aqueous solutions with different ionic strengths ( 0 . 01 - 1000 m ) and / or different phs ( 1 - 14 ), depending on the origin of the gelatine used , at a temperature from 20 ° to 90 ° c . under stirring ( magnetic , orbital , mechanical or other ). the gelatine may be of animal , microbial or vegetal origin from the different types a , b , i , ii , iii , iv . the organic salts may be in the liquid or solid state and are chiral or achiral . a ) halides ( cl , br , i , f ), phosphites and phosphates ( pf 6 , h 2 po 2 h 2 po 4 , po 3 ), borates ( bf 4 , bo 2 , bo 3 ), nitrites and nitrates ( no 3 , no 2 ), sulphates ( hso 4 ), cyanides and cyanates ( cn , scn , cno ), cyanamides ( c 2 n 3 ), dicyanamide ( n ( cn ) 2 ), azides ( n 3 ), carbonates ( hco 3 ), bromates ( bro 3 ), iodates ( io 3 , io 4 ), chlorites and chlorates ( cl 2 o 3 , clo 4 , clo 2 , clo ); b ) metal halides such as zncl 3 , znbr 3 , sncl 5 , snbr 5 , fecl 4 , febr 4 , nicl 3 , aubr 4 , aubr 4 , aucl 4 , gacl 4 , alcl 4 , al 2 cl 7 , al3cl 10 ; c ) compounds which include other elements of the periodic table , preferably from the groups ib to viib , groups iiia to via and group viii , more preferably including elements such as arsenic ( asf 6 , h 2 aso 3 , aso 2 ), antimony ( sbf 6 , sbo 3 ), chromium ( hcro 4 ), tellurium ( hteo 6 , hteo 3 ), selenium ( hseo 3 , secn ), niobium ( nbo 3 ), thallium ( tao 3 ), ruthenium ( ruo 4 ), manganese ( mno 4 ) and rhenium ( reo 4 ), bismuth ( bio 3 ), vanadium ( vo 4 ) and silver ( ag ( cn ) 2 ); a ) carboxylates , thiocarboxylates , carbamates , dithiocarbamates , xanthates , sulphonates , organosulfates , organosulfamates , organophosphates , phosphonates , thiophosphonates and other compounds having the general formula r 1 - z - y − ( ii ) wherein z is cy , so 2 , p ( y ) r 2 or as ( y ) r 2 ; y is , independently for each occurrence , o or s ; and r 1 and r 2 are equal or different radicals defined as : a1 ) h — or e -, in which e is f , cl , oh , nh 2 or sh ; a2 ) a hydrocarbon radical of 1 to 30 carbon atoms , optionally including double or triple bonds and / or 1 or more saturated , unsaturated or aromatic rings ; a3 ) a radical having the same meaning as in a2 ) but wherein 1 to 15 ch 2 units were substituted by equal or different di - radicals , selected from o , nr 3 , s , so , so 2 , co , sir 3 r 4 or p ( o ) r 3 , the radicals r 3 and r 4 being as defined in paragraphs a1 ), a2 ), a3 ), a4 ) and a5 ); a4 ) a radical having the same meaning as in a2 ) or a3 ), wherein 1 to 15 ch units were substituted by equal or different tri - radicals selected from n , sir 5 or po , r 5 being a radical as defined in paragraphs a1 ), a2 ), a3 ), a4 ) and a5 ); a5 ) a radical having the same meaning as in a2 ), a3 ) or a4 ), wherein one or more h atoms were substituted by f , cl , br , i , oh , sh or nh 2 ; being understood that , in case there is a group r 2 in ( ii ), it can be connected to r 1 by one or more single , double or triple covalent bonds , forming one or more rings , including aromatic rings ; b ) imides , thioimides , sulfonimides , n - acyl - sulfonamides , n - acyl - phosphoramides and other compounds of general formula wherein z is cy , so 2 , p ( y ) r 2 or as ( y ) r 2 ; y is , independently for each occurrence , o or s ; and r 1 and r 2 are , independently for each occurrence , equal or different radicals as defined in paragraphs a1 ), a2 ), a3 ), a4 ) and a5 ), being understood that in ( iii ) the groups r 1 , and r 2 if existing , are connected to each other by one or more single , double or triple covalent bonds , forming one or more rings , including aromatic rings ; c ) ascorbates , barbiturates , ferrocenecarboxylates , isocyanurates , oxaloacetates , methane - fullerene carboxylates , and mixtures of the compounds mentioned in paragraphs a ) and b ); a1 ) heterocycles of charge centered in the sulphur , phosphorous , nitrogen , oxygen atoms such as phosphonium , ammonium ( including chirals ), sulfonium , pyridinium , 8 - alkyl - 1 , 8 - diazabicyclo [ 5 , 4 , 0 ]- 7 - undecenium [ alkyl - dbu ], 1 , 2 - dialkylimidazolium , 1 , 3 - dialkylimidazolium , 1 , 2 , 3 - trialkylimidazolium , monoalkyl - dialkylguanidinium , trialkyl - dialkylguanidinium , tetraalkyl - dialkylguanidinium , pentaalkyl - dialkylguanidinium , hexaalkyl - dialkylguanidinium ; a2 ) compounds including other elements of the periodic table , preferably alkaline - earth metals . the new materials based on gelatine and organic salts are , preferably , in the form of a : i ) solid ( fibre , nanofibre , particle , nanoparticle , film , nanofilm , among others ) ii ) liquid iii ) colloid ( emulsion , foam , gel , aerosol , aerogel , among others ) a second object of the invention is the use of the new materials based on gelatine and organic salts , synthesized as referred to above , selected from one of the following uses : a ) as cell growth medium , b ) in the manufacturing of biosensors and electrodes for bioelectrochemical applications , c ) in the immobilization of chemical and biological catalysts so that chemical reactions are performed , d ) for the impregnation and / or encapsulation of substances having pharmacological properties , e ) as catalysts for chemical transformation reactions in aqueous and non - aqueous media , f ) in the manufacturing and modification of fibres for incorporation of electronic devices into textiles , g ) in electrochemical ( galvanic or electrolytic ) cells or parts of cells , including fuel cells , so that they can act as conductors or semiconductors , h ) for the manufacture of photovoltaic cells that can act as immobilization matrix for photosynthetic cells , conductive or semi - conductive or electrolytic material , i ) as a new type of membrane employed in the selective transport of different organic molecules ( such as alcohols , amines , ethers , esters , carboxylic acids ), peptides , amino acids , sugars , anthocyanines , nucleic acids and other compounds of chemical , biochemical or pharmaceutical interest , and j ) as immobilization matrix for cells ( of microbial , vegetal and animal origin ) in the manufacture of compounds with chemical , biochemical or pharmaceutical interest . to 540 mg of bmimcl is added a portion of 100 mg of gelatine under magnetic stirring at a temperature in the range from 40 to 90 ° c ., most preferably at 65 ° c . this mixture shall remain over a period of no less than 60 minutes , most preferably 30 minutes , until it is perfectly homogenous . the mixture is cooled to a temperature from 20 ° to 40 ° c . water is added so that the concentration of salt is from 1 to 250 m , most preferably 155 m . it shall be checked if the ph is at a value from 5 to 9 . gelatine is gradually added in order to keep the salt / gelatine ratio ( w / w ) in the range from 0 . 1 to 10 , most preferably 1 . 4 . the stirring continues until the mixture is homogenous and then it is allowed to solidify . cross - linking between gelatine and 1 - butyl 3 methyl imidazolium dicyanamide salt ( bmimdca ) to 300 μl of bmimdca is added a portion of 30 mg of gelatine under magnetic stirring at a temperature in the range from 40 to 90 ° c ., most preferably 70 ° c . this mixture shall remain over a period of no less than 60 minutes , most preferably 30 minutes , until it is perfectly homogenous . the mixture is cooled to a temperature from 20 ° to 40 ° c . water is added so that the concentration of salt is from 1 to 250 m , most preferably 24 m . it shall be checked if the ph is at a value from 5 to 9 . gelatine is gradually added in order to keep the salt / gelatine ratio ( w / w ) in the range from 0 . 1 to 10 , most preferably 1 . 4 . the stirring continues until the mixture is homogenous and then it is allowed to solidify . to 300 μl of bmimsaccharin is added a portion of 30 mg of gelatine under magnetic stirring at a temperature in the range from 40 to 90 ° c ., most preferably 70 ° c . this mixture shall remain over a period of no less than 60 minutes , most preferably 45 minutes , until it is perfectly homogenous . the mixture is cooled to a temperature from 20 ° to 40 ° c . water is added so that the concentration of salt is from 1 to 250 m , most preferably 14 m . it shall be checked if the ph is at a value from 5 to 9 . gelatine is gradually added in order to keep the salt / gelatine ratio ( w / w ) is in the range from 0 . 1 to 10 , most preferably 0 . 8 . the stirring continues until the mixture is homogenous and then it is allowed to solidify . to 200 μl of aliqdca is added a portion of 20 mg of gelatine under magnetic stirring at a temperature in the range from 40 to 90 ° c ., most preferably 60 ° c . this mixture shall remain over a period of no less than 60 minutes , most preferably 45 minutes , until it is perfectly homogenous . the mixture is cooled to a temperature from 10 ° to 40 ° c . water is added so that the concentration of salt is from 0 . 5 to 800 m , most preferably 150 m . it shall be checked if the ph is at a value from 5 to 9 . gelatine is gradually added in order to keep the salt / gelatine ratio ( w / w ) in the range from 1 to 50 . the stirring continues until the mixture is homogenous and then it is allowed to solidify . to 200 μl of omimdca is added a portion of 20 mg of gelatine under magnetic stirring at a temperature in the range from 20 to 90 ° c . this mixture shall remain over a period of no less than 60 minutes , most preferably 30 minutes , until it is perfectly homogenous . the mixture is cooled to a temperature from 10 ° to 40 ° c . water is added so that the concentration of salt is from 0 . 5 to 500 m , most preferably 30 m . it shall be checked if the ph is at a value from 5 to 9 . gelatine is gradually added in order to keep the salt / gelatine ratio ( w / w ) in the range from 1 to 50 , most preferably 5 . the stirring continues until the mixture is homogenous and then it is allowed to solidify . to 210 μl of omimdca is added a portion of 20 mg of gelatine under magnetic stirring at a temperature in the range from 20 to 90 ° c . this mixture shall remain over a period of no less than 60 minutes , most preferably 30 minutes , until it is perfectly homogenous . the mixture is cooled to a temperature from 10 ° to 40 ° c . water is added so that the concentration of salt is from 1 to 250 m , most preferably 6 m . it shall be checked if the ph is at a value from 5 to 9 . gelatine is gradually added in order to keep the salt / gelatine ratio ( w / w ) in the range from 0 . 1 to 10 . the stirring continues until the mixture is homogenous and then it is allowed to solidify . 100 mg of nadca are dissolved in 190 μl of water under magnetic stirring and at a temperature in the range from 20 to 90 ° c ., preferably 35 ° c ., in order to provide a solution 11 . 2 m . this mixture shall remain under stirring until it gives a perfectly homogenous solution . the mixture is cooled to a temperature from 10 ° to 40 ° c . it shall be checked if the ph is at a value from 5 to 9 . gelatine is gradually added in order to keep the salt / gelatine ratio ( w / w ) in the range from 0 . 1 to 100 , most preferably 0 . 9 . the stirring continues until the mixture is homogenous . the material shall be dried according to the desired application . therefore , it can be done by hot air drying , with a temperature from 20 to 90 ° c ., most preferably 35 ° c ., under vacuum , lyophilisation or supercritical extraction . 500 mg of nasaccharin are dissolved in 450 μl of water under magnetic stirring and at a temperature in the range from 20 to 90 ° c ., preferably 35 ° c ., in order to provide a solution 11 . 2 m . this mixture shall remain under stirring until it gives a perfectly homogenous solution . the mixture is cooled to a temperature from 20 ° to 40 ° c . it shall be checked if the ph is at a value from 5 to 9 . gelatine is gradually added in order to keep the salt / gelatine ratio ( w / w ) in the range from 0 . 1 to 10 , most preferably 1 . 7 . the stirring continues until the mixture is homogenous . the material shall be dried according to the desired application . therefore , it can be done by hot air drying , with a temperature from 25 to 90 ° c ., most preferably 35 ° c ., under vacuum , lyophilisation or supercritical extraction . to 200 μl of aliquat 336 ® is added a portion of 20 mg of gelatine under magnetic stirring and at a temperature in the range from 20 ° to 90 ° c ., most preferably 60 ° c . this mixture shall remain over a period of no less than 60 minutes , most preferably 30 minutes , until it is perfectly homogenous . the mixture is cooled to a temperature from 10 ° to 40 ° c . water is added so that the concentration of salt is from 0 . 5 to 800 m , most preferably 150 m . it shall be checked if the ph is at a value from 5 to 9 . gelatine is gradually added in order to keep the salt / gelatine ratio ( w / w ) in the range from 1 to 50 . the stirring continues 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