CN114262273A - Novel degradable quaternary ammonium salt with high antibacterial activity and synthesis method thereof - Google Patents
Novel degradable quaternary ammonium salt with high antibacterial activity and synthesis method thereof Download PDFInfo
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Abstract
The invention discloses a novel degradable quaternary ammonium salt with high antibacterial activity and a synthesis method thereof, which comprises the steps of firstly reacting chloroacetyl chloride with ethylene glycol, butanediol or hexanediol to synthesize intermediates with the lengths N of spacers of 2, 4 and 6 respectively, and then reacting the intermediates with N, N-dimethyloctane-1-amine, N-dimethyldecane-1-amine, N-dimethyldodecane-1-amine or N, N-dimethyltetradecane-1-amine with the lengths m of hydrophobic alkyl chains of 8, 10, 12 and 14 respectively to obtain the gemini esterquat with the length m of the hydrophobic alkyl chains and the length N of the spacers. The synthesized gemini esterquat can be used as an antibacterial material, has high antibacterial activity, can be decomposed in water at normal temperature, and can kill bacteria by more than 99% before complete degradation compared with antibacterial kinetics and degradation kinetics.
Description
Technical Field
The invention relates to a novel degradable quaternary ammonium salt material with high antibacterial activity and a preparation method thereof, belonging to the field of sterilization.
Background
In the development of the current industry, due to the functional limitations of the oxidizing germicides and the generation of resistant bacteria and the limitation of environmental protection, the work of developing novel, environmental-friendly and multifunctional non-oxidizing germicides is gradually increasing. In the 30 s of the 20 th century, quaternary ammonium salt has attracted attention as a bactericide, and although single-chain quaternary ammonium salt bactericides developed in the early days have good bactericidal effects, certain defects of the bactericide, such as drug resistance, narrow biocidal spectrum and the like, gradually appear in the follow-up period. Therefore, double-chain quaternary ammonium salt bactericides are developed through successive research at home and abroad. Although the double-chain quaternary ammonium salt biocide attracts the attention of a plurality of researchers through the special structure and unique properties, the double-chain quaternary ammonium salt biocide is still a small-molecular quaternary ammonium salt and has the defects of easy volatilization, poor chemical stability, residual toxicity, short sterilization time and the like.
In order to overcome the defects of the double-chain small-molecule quaternary ammonium salt, a gemini quaternary ammonium salt is developed subsequently, wherein the gemini quaternary ammonium salt is an organic salt with two nitrogen positive ions, and has higher charge density, better degradation performance, biocompatibility and the like compared with the double-chain quaternary ammonium salt. The gemini quaternary ammonium salt has various types, and different types of gemini quaternary ammonium salts can be obtained by changing the properties of the hydrophilic head group, the lengths of the hydrophobic chain and the connecting group and the rigidity and flexibility or introducing chemical groups with special functions according to needs, so that the gemini quaternary ammonium salt has richer structures and more excellent performance. The diester group is introduced into the gemini quaternary ammonium salt, so that the quaternary ammonium salt has better biodegradability and biocompatibility, and the bactericidal performance of the quaternary ammonium salt to drug-resistant bacteria is expected to be improved.
Disclosure of Invention
The invention aims to provide a novel degradable quaternary ammonium salt with high antibacterial activity and a synthesis method thereof, and aims to obtain a quaternary ammonium salt antibacterial material with excellent antibacterial effect and degradation performance by changing the lengths of a hydrophobic chain and a spacer.
In order to achieve the purpose, the invention adopts the following technical scheme:
a method for synthesizing novel degradable quaternary ammonium salt with high antibacterial activity is characterized in that: firstly, reacting chloroacetyl chloride with ethylene glycol, butanediol or hexanediol to synthesize intermediates with the length N of a spacer group of 2, 4 and 6 respectively, and then reacting the intermediates with N, N-dimethyloctane-1-amine, N-dimethyldecane-1-amine, N-dimethyldodecane-1-amine or N, N-dimethyltetradecane-1-amine with the length m of a hydrophobic alkyl chain of 8, 10, 12 and 14 respectively to obtain the gemini ester group quaternary ammonium salt with the length m of the hydrophobic alkyl chain and the length N of the spacer group. The method specifically comprises the following steps:
and 2, adding N, N-dimethyloctane-1-amine, N-dimethyldecane-1-amine, N-dimethyldodecane-1-amine or N, N-dimethyltetradecane-1-amine into a three-necked flask, adding acetone or dichloromethane serving as a solvent, dropwise adding the intermediate obtained in the step 1, carrying out reflux reaction at 40-50 ℃ for 6-24h, carrying out suction filtration, carrying out recrystallization purification on the product, and carrying out vacuum drying at 50-80 ℃ to obtain the product, namely the diester-based quaternary ammonium salt.
In step 1, the molar ratio of ethylene glycol, butanediol or hexanediol to chloroacetic chloride is 1: 2-3, and the molar ratio of ethylene glycol, butanediol or hexanediol to chloroacetic acid is 1: 1.
Further, in the step 2, the molar ratio of the N, N-dimethyloctane-1-amine, the N, N-dimethyldecane-1-amine, the N, N-dimethyldodecane-1-amine or the N, N-dimethyltetradecane-1-amine to the intermediate is 2: 4-7.
Further, in step 1, the dropping speed of chloroacetyl chloride is 1-2 seconds per drop.
Further, in step 2, the dropping rate of the intermediate is 1 to 2 seconds per drop.
The invention has the beneficial effects that:
1. the gemini esterquat synthesized by the invention can be used as an antibacterial material, has high antibacterial activity, can be decomposed in water at normal temperature, and can kill more than 99% of bacteria before the degradation is finished compared with antibacterial kinetics and degradation kinetics.
2. The method can synthesize a series of quaternary ammonium salts with different molecular weights, and has the advantages of low reaction temperature, low energy consumption, high yield, simple method and low manufacturing cost.
3. The invention verifies that the obtained gemini esterquat has good biodegradability by adopting an activated sludge degradation method, is closer to the actual water condition and is environment-friendly.
Drawings
FIG. 1 shows the intermediates obtained in examples 1 to 3 of the present invention1H NMR chart in which 1,2 and 3 correspond to the intermediates ethane-1, 2-diylbis (2-chloroacetic acid), butane-1, 4-diylbis (2-chloroacetic acid) or hexane-1, 6-diylbis (2-chloroacetic acid), respectively;
FIG. 2 shows Q having different carbon chain lengths obtained in example 1 of the present inventionm-2-mIs/are as follows1HNMR map, wherein each of the maps a, b, c, d is Q8-2-8、Q10-2-10、Q12-2-12、Q14-2-14Is/are as follows1A HNMR map;
FIG. 3 shows Q of different carbon chain lengths obtained in example 2 of the present inventionm-4-mIs/are as follows1HNMR map, wherein each of the maps a, b, c, d is Q8-4-8、Q10-4-10、Q12-4-12、Q14-4-14Is/are as follows1A HNMR map;
FIG. 4 shows Q having different carbon chain lengths obtained in example 3 of the present inventionm-6-mIs/are as follows1HNMR map, in which 1,2, 3 and 4 are Q8-6-8、Q10-6-10、Q12-6-12、Q14-6-14Is/are as follows1A HNMR map;
FIG. 5 shows Q obtained in example 1 of the present inventionm-2-mAn antibacterial rate map of;
FIG. 6 shows Q obtained in example 2 of the present invention10-4-10、Q12-4-12Comparing the antibacterial efficiency;
FIG. 7 shows Q obtained in example 3 of the present inventionm-6-mAn antibacterial rate map of;
FIG. 8 shows Q obtained in example 1 of the present inventionm-2-mThe degradation curve of (d);
FIG. 9 shows Q obtained in example 2 of the present inventionm-4-mDegradation curve of (2).
Detailed Description
The following examples are given for the detailed implementation and specific operation of the present invention, but the scope of the present invention is not limited to the following examples.
Example 1 Gemini ester Quaternary ammonium salt Qm-2-mSynthesis of (2)
This example prepares gemini esterquat Q as followsm-2-m：
Adding 6.2g of ethylene glycol into a three-neck flask, adding 9.45g of chloroacetic acid, dropwise adding 24.85g of chloroacetic chloride at the speed of 1-2 seconds per drop, carrying out reflux reaction at 55 ℃ for 2 hours, pouring the obtained reaction system into ice water, and carrying out suction filtration to obtain a crude product; finally washing the product with saturated brine and sodium carbonate solution, vacuum drying at 70 ℃ to obtain an intermediate ethane-1, 2-diylbis (2-chloroacetic acid),1HNMR(400MHz,Chloroform-d)δ4.44–4.38(m,4H),4.13–4.04(m,4H)。
Adding 4.72g of N, N-dimethyloctane-1-amine into a three-neck flask, adding 25mL of acetone, uniformly mixing 2.58g of ethane-1, 2-diylbis (2-chloroacetic acid) with 25mL of acetone, dropwise adding into the three-neck flask at the speed of 1-2 seconds/drop, carrying out reflux reaction at 45 ℃ for 6 hours, carrying out suction filtration, and adding Dichloromethane (DCM) and petroleum ether in a volume ratio of 1: 5, recrystallizing and purifying the product, and drying the product in vacuum at 50 ℃ to obtain the product gemini esterquat Q8-2-8。
5.56g of N, N-dimethyldecan-1-amine are taken and introduced into a three-necked flask, 25mL of acetone are added, and 2.58g of ethane-1, 2-diylbis (2-chloroacetic acid) and 25m are introducedAnd (3) uniformly mixing L acetone, dropwise adding the mixture into a three-neck flask at the speed of 1-2 seconds per drop, carrying out reflux reaction at 45 ℃ for 8 hours, carrying out suction filtration, and mixing DCM and petroleum ether in a volume ratio of 1: 5, recrystallizing and purifying the product, and drying the product in vacuum at 50 ℃ to obtain the product gemini esterquat Q10-2-10。
Adding 6.40g N, N-dimethyldodecane-1-amine into a three-necked flask, adding 25mL of acetone, uniformly mixing 2.58g of ethane-1, 2-diylbis (2-chloroacetic acid) with 25mL of acetone, dropwise adding into the three-necked flask at the speed of 1-2 seconds/drop, carrying out reflux reaction at 45 ℃ for 14 hours, carrying out suction filtration, and adding DCM and petroleum ether in a volume ratio of 1: 5, recrystallizing and purifying the product, and drying the product in vacuum at 50 ℃ to obtain the product gemini esterquat Q12-2-12。
Adding 7.24g N, N-dimethyltetradecane-1-amine into a three-neck flask, adding 25mL of acetone, uniformly mixing 2.58g of ethane-1, 2-diylbis (2-chloroacetic acid) and 25mL of acetone, dropwise adding into the three-neck flask at the speed of 1-2 seconds/drop, carrying out reflux reaction at 45 ℃ for 24 hours, carrying out suction filtration, and adding DCM and petroleum ether in a volume ratio of 1: 5, recrystallizing and purifying the product, and drying the product in vacuum at 50 ℃ to obtain the product gemini esterquat Q14-2-14。
FIG. 2 shows four Q values in this examplem-2-mIs/are as follows1HNMR picture, from which the structure is consistent with the spectrogram.
Q8-2-8，1H NMR(400MHz,Chloroform-d)δ5.49(s,4H),4.45(s,4H),3.83–3.75(m,4H),3.52(s,12H),1.75(dd,J＝10.8,6.3Hz,4H),1.35–1.16(m,20H),0.84(t,J＝6.8Hz,6H).
Q10-2-10，1H NMR(400MHz,Chloroform-d)δ5.47(s,4H),4.44(s,4H),3.82–3.73(m,4H),3.51(s,11H),1.73(dd,J＝10.7,5.5Hz,4H),1.33–1.22(m,14H),1.20(s,14H),0.83(t,J＝6.7Hz,6H).
Q12-2-12，1H NMR(400MHz,Chloroform-d)δ5.37(s,4H),4.48–4.42(m,4H),3.76(dd,J＝11.3,5.7Hz,4H),3.52–3.47(m,12H),1.70(d,J＝5.7Hz,4H),1.29(d,J＝16.6Hz,12H),1.24–1.18(m,26H),0.84(dd,J＝9.5,5.6Hz,6H).
Q14-2-14，1H NMR(400MHz,Chloroform-d)δ5.46(s,4H),4.45(s,3H),3.82–3.73(m,4H),3.51(s,12H),1.75(t,J＝8.4Hz,4H),1.35–1.22(m,44H),0.85(t,J＝6.7Hz,6H).
Example 2
This example prepares Q as followsm-4-mQuaternary ammonium salts:
Adding 9.01g of butanediol into a three-neck flask, adding 9.45g of chloroacetic acid, dropwise adding 24.85g of chloroacetic chloride at the speed of 1-2 seconds per drop, carrying out reflux reaction at 55 ℃ for 3 hours, pouring the obtained reaction system into ice water, and carrying out suction filtration to obtain a crude product; finally washing the product with saturated brine and sodium carbonate solution, vacuum drying at 70 ℃ to obtain an intermediate butane-1, 4-diylbis (2-chloroacetic acid) product,1HNMR(400MHz,Chloroform-d)δ4.26–4.19(m,4H),4.05(t,J＝2.4Hz,4H),1.76(q,J＝3.8,3.4Hz,4H)。
Adding 4.72g of N, N-dimethyloctane-1-amine into a three-neck flask, adding 25mL of dichloromethane, uniformly mixing 3g of butane-1, 4-diylbis (2-chloroacetic acid) and 25mL of dichloromethane, dropwise adding into the three-neck flask at the speed of 1-2 seconds/drop, carrying out reflux reaction at 45 ℃ for 8 hours, and reacting with DCM (DCM) and petroleum ether in a volume ratio of 1: 5, recrystallizing and purifying the product, and drying the product in vacuum at 50 ℃ to obtain the product gemini esterquat Q8-4-8。
Adding 5.56g of N, N-dimethyldecane-1-amine into a three-neck flask, adding 25mL of dichloromethane, uniformly mixing 3g of butane-1, 4-diylbis (2-chloroacetic acid) and 25mL of dichloromethane, dropwise adding into the three-neck flask at the speed of 1-2 seconds/drop, carrying out reflux reaction at 45 ℃ for 12 hours, and reacting with DCM (DCM) and petroleum ether in a volume ratio of 1: 5, recrystallizing and purifying the product, and drying the product in vacuum at 50 ℃ to obtain the product gemini esterquat Q10-4-10。
Adding 6.40g of N, N-dimethyldodecane-1-amine into a three-neck flask, adding 25mL of dichloromethane, uniformly mixing 3g of butane-1, 4-diylbis (2-chloroacetic acid) and 25mL of dichloromethane, dropwise adding into the three-neck flask at the speed of 1-2 seconds/drop, carrying out reflux reaction at 45 ℃ for 12 hours, and using DCM and petroleum ether in a volume ratio of1: 5, recrystallizing and purifying the product, and drying the product in vacuum at 50 ℃ to obtain the product gemini esterquat Q12-4-12。
Adding 7.24g of N, N-dimethyltetradecane-1-amine into a three-neck flask, adding 25mL of dichloromethane, uniformly mixing 3g of butane-1, 4-diylbis (2-chloroacetic acid) and 25mL of dichloromethane, dropwise adding into the three-neck flask at the speed of 1-2 seconds/drop, carrying out reflux reaction at 45 ℃ for 14h, and reacting with DCM (DCM) and petroleum ether in a volume ratio of 1: 5, recrystallizing and purifying the product, and drying the product in vacuum at 50 ℃ to obtain the product gemini esterquat Q14-4-14。
FIG. 3 shows four Q values in this embodimentm-4-mIs/are as follows1H NMR chart, as shown, compares with Q in the vicinity of. delta. ═ 1.8m-2-mA new group of peaks is added, and other peaks and Qm-2-mMore similarly, the visible structure coincides with the spectrogram.
Q8-4-8，1HNMR(400MHz,Chloroform-d)δ5.59(d,J＝2.9Hz,4H),4.14(d,J＝4.2Hz,4H),3.84–3.75(m,4H),3.55(s,12H),1.86(d,J＝4.2Hz,4H),1.74(s,4H),1.41–1.11(m,20H),0.86(t,J＝6.6Hz,6H).
Q10-4-10，1H NMR(400MHz,)δ4.77(s,4H),3.35(t,J＝4.5Hz,4H),3.04–2.95(m,4H),2.75(s,12H),1.05(d,J＝4.5Hz,4H),1.00–0.91(m,4H),0.48(d,J＝37.8Hz,28H),0.06(d,J＝6.5Hz,6H).
Q12-4-12，1H NMR(400MHz,Chloroform-d)δ5.43(s,4H),4.14(d,J＝4.9Hz,4H),3.81–3.73(m,4H),3.52(s,12H),1.79(s,4H),1.76–1.67(m,4H),1.24(d,J＝38.2Hz,36H),0.82(t,J＝6.8Hz,6H).
Q14-4-14，1H NMR(400MHz,Chloroform-d)δ5.53(s,4H),4.14(d,J＝4.7Hz,4H),3.83–3.74(m,4H),3.54(s,12H),1.82(d,J＝4.6Hz,4H),1.78–1.70(m,4H),1.30(d,J＝4.6Hz,8H),1.21(s,36H),0.84(t,J＝6.7Hz,6H).
Example 3
This example prepares Q as followsm-6-mQuaternary ammonium salts:
Take 11.8gAdding butanediol into a three-neck flask, adding 9.45g of chloroacetic acid, then dropwise adding 24.85g of chloroacetic chloride at the speed of 1-2 seconds per drop, carrying out reflux reaction at 55 ℃ for 3 hours, pouring the obtained reaction system into ice water, and carrying out suction filtration to obtain a crude product; finally washing the product with saturated brine and sodium carbonate solution, vacuum drying at 70 ℃ to obtain an intermediate hexane-1, 6-diylbis (2-chloroacetic acid) product,1H NMR(400MHz,Chloroform-d)δ4.20–4.11(m,2H),4.03(d,J＝3.0Hz,2H),1.69–1.62(m,2H),1.38(p,J＝3.8Hz,2H).
Adding 4.72g of N, N-dimethyloctane-1-amine into a three-neck flask, adding 25mL of dichloromethane, uniformly mixing 3.25g of hexane-1, 6-diylbis (2-chloroacetic acid) and 25mL of acetone, dropwise adding into the three-neck flask at the speed of 1-2 seconds/drop, carrying out reflux reaction at 45 ℃ for 10 hours, and reacting with DCM (DCM) and petroleum ether in a volume ratio of 1: 5, recrystallizing and purifying the product, and drying the product in vacuum at 50 ℃ to obtain the product gemini esterquat Q8-6-8。
Adding 5.56g of N, N-dimethyldecane-1-amine into a three-necked flask, adding 25mL of dichloromethane, uniformly mixing 3.25g of hexane-1, 6-diylbis (2-chloroacetic acid) and 25mL of acetone, dropwise adding into the three-necked flask at the speed of 1-2 seconds/drop, carrying out reflux reaction at 45 ℃ for 12 hours, and reacting with DCM (DCM) and petroleum ether in a volume ratio of 1: 5, recrystallizing and purifying the product, and drying the product in vacuum at 50 ℃ to obtain the product gemini esterquat Q10-6-10。
Adding 6.40g N, N-dimethyldodecane-1-amine into a three-neck flask, adding 25mL of dichloromethane, uniformly mixing 3.25g of hexane-1, 6-diylbis (2-chloroacetic acid) and 25mL of acetone at the speed of 1-2 seconds/drop, dropwise adding into the three-neck flask, carrying out reflux reaction at 45 ℃ for 12 hours, and reacting with DCM (DCM) and petroleum ether in a volume ratio of 1: 5, recrystallizing and purifying the product, and drying the product in vacuum at 50 ℃ to obtain the product gemini esterquat Q12-6-12。
Adding 7.24g N, N-dimethyltetradecane-1-amine into a three-neck flask, adding 25mL of dichloromethane, uniformly mixing 3.25g of hexane-1, 6-diylbis (2-chloroacetic acid) and 25mL of acetone at the speed of 1-2 seconds/drop, dropwise adding into the three-neck flask, and carrying out reflux reaction at 45 DEG CAnd 24h, mixing DCM with petroleum ether in a volume ratio of 1: 5, recrystallizing and purifying the product, and drying the product in vacuum at 50 ℃ to obtain the product gemini esterquat Q14-6-14。
FIG. 4 shows four Q values in this embodimentm-6-mIs/are as follows1H NMR chart, as shown, compares with Q in the vicinity of. delta. ═ 1.8m-2-mA new group of peaks are added, and the value near delta to 1.9 is better than that of Qm-4-mA new group of peaks is added, and other peaks and Qm-2-mMore similarly, the visible structure coincides with the spectrogram. With the exception of Q10-6-10Is difficult to purify and has obvious hetero peaks compared with the structures of other three quaternary ammonium salts
Q8-6-8，1H NMR(400MHz,Chloroform-d)δ5.44(s,4H),4.18(t,J＝5.3Hz,4H),3.82–3.73(m,4H),3.55(s,12H),1.80–1.62(m,8H),1.58–1.49(m,4H),1.35–1.17(m,20H),0.84(t,J＝6.7Hz,6H).
Q10-6-10，1H NMR(400MHz,Chloroform-d)δ5.30(s,4H),4.18(t,J＝5.4Hz,4H),3.80–3.71(m,4H),3.42(s,12H),1.74(s,4H),1.66(s,4H),1.51(s,4H),1.30(s,4H),1.22(s,20H),0.84(t,J＝6.8Hz,6H).
Q12-6-12，1H NMR(400MHz,Chloroform-d)δ5.48(s,4H),4.20(t,J＝5.3Hz,4H),3.83–3.74(m,4H),3.56(s,12H),1.76(q,J＝5.4Hz,4H),1.68(d,J＝5.3Hz,4H),1.59–1.51(m,4H),1.31(d,J＝4.9Hz,8H),1.23(s,28H),0.86(t,J＝6.7Hz,6H).
Q14-6-14，1H NMR(400MHz,Chloroform-d)δ5.48(s,4H),4.23–4.16(m,4H),3.83–3.74(m,4H),3.56(s,12H),1.75(s,4H),1.68(t,J＝5.4Hz,4H),1.55(s,4H),1.31(d,J＝5.3Hz,8H),1.23(s,36H),0.86(t,J＝6.7Hz,6H).
The degradable gemini esterquat antibacterial material prepared in each embodiment is applied to killing of harmful microorganisms in water environment, taking escherichia coli as an example, and the specific test method is as follows: the antimicrobial activity was evaluated using the measurement of the Minimum Inhibitory Concentration (MIC). Various concentrations of quaternary ammonium salt solutions (1024, 512, 256, 128, 64, 32, 16, 8, 4 and 2 μ g/mL) were prepared using 0.9% sterile saline. The concentration of Escherichia coli is 5 × 105CFU/mL of 50. mu.L TSB (Trypsin)Enzyme soy broth) solution was added to a 96 well microtiter plate, followed by 350 μ L of quaternary ammonium salt solution. 400 μ L of 0.9% sterile saline was used as a negative control, and 350 μ L of 0.9% sterile saline and 50 μ L of test organism were used as positive controls. The 96-well plates with the test organisms were incubated at 37 ℃ for 24 hours. The lowest concentration of the quaternary ammonium salt solution without turbidity was the MIC, as shown in table 1.
TABLE 1
Then preparing quaternary ammonium salt into solution with corresponding concentration according to MIC value, taking 200 mu L and 200 mu L of isovolumetric bacterial liquid (about 5 multiplied by 10)5CFU/mL), incubating at 37 deg.C for 5min, 10min, 15min, 30min, and 60min, and spreading 20 μ L. Another 20. mu.L of the bacterial liquid is diluted to 2mL, and 20. mu.L of the diluted bacterial liquid is coated on a flat plate to serve as a blank control. And (3) inversely culturing the coated flat plate in a biological incubator for 12h, counting the number of colonies before and after coating the flat plate by a counting method, and qualitatively evaluating the antibacterial performance of the quaternary ammonium salt.
FIG. 5 shows Q in example 1m-2-mAntimicrobial kinetics of antimicrobial material, wherein Q8-2-8The MIC value of (1) is too large, no test value exists, so the antibacterial dynamics of the other three quaternary ammonium salts are tested, the conditions that the plate is coated and incubated at 37 ℃ for 12 hours after different quaternary ammonium salts and bacterial liquid are jointly processed for 5min, 10min, 15min, 30min and 60min are respectively carried out from left to right, the number of the bacterial colonies counted in a blank group is 315CFU, the bacterial colonies counted before dilution is 31500CFU, namely the concentration of the test bacterial liquid is 3.15 x106CFU/mL. The colony number is greatly reduced after 5min treatment, and the sterilization rate can reach more than 99.9% after 10min treatment. It can be seen that the antibacterial process of the quaternary ammonium salt material can kill more than 99.9% of Escherichia coli within 10 min.
FIG. 6 shows Q in example 210-4-10、Q12-4-12Two quaternary ammonium salts at equal MIC valuesAnd (3) performing antibacterial dynamics test, namely respectively treating the two quaternary ammonium salts and the bacterial liquid from left to right for 5min, 10min, 15min, 30min and 60min, coating a flat plate, incubating at 37 ℃ for 12h, counting the number of blank groups of bacterial colonies to be 51CFU, and before dilution to be 5100CFU, namely testing the concentration of the bacterial liquid to be 2.5x105CFU.mL-1. After 5min treatment Q12-4-12The colony number is greatly reduced, and the sterilization rate can reach more than 99.8 percent after 10min treatment. Q10-4-10The performance is inferior to Q12-4-12However, the sterilization rate of 93.63% was also achieved after 30min treatment.
FIG. 7 shows Q in example 3m-6-mKinetics of antibacterial action of antibacterial material due to Q10-6-10Difficult purification, so the antibacterial dynamics of the other three quaternary ammonium salts are tested, the conditions that the plate is coated and incubated at 37 ℃ for 12h after different quaternary ammonium salts and bacterial liquid are jointly processed for 5min, 10min, 15min, 30min and 60min respectively from left to right are shown, the number of the bacterial colonies in a blank group is counted to be 27CFU, the bacterial colonies before dilution is 2700CFU, namely the concentration of the tested bacterial liquid is 1.35 x105CFU/mL. Wherein Q12-6-12、Q14-6-14After 5min treatment, the number of viable bacteria was greatly reduced.
Q8-6-8Compared with Q8-2-8、Q8-4-8The MIC value of the quaternary ammonium salt is greatly reduced, and the antibacterial effect of the quaternary ammonium salt with the spacer of 6 is better than that of the quaternary ammonium salt with the spacers of 2 and 4, wherein the length of the hydrophobic chain segment also has certain influence on the antibacterial effect.
The degradation performance of the quaternary ammonium salt obtained in each embodiment is tested according to the GBT-5174-2018 standard, and the specific steps are as follows:
And drawing a standard curve of each gemini esterquat by taking the maximum absorbance at 485nm as the ordinate and the concentration as the abscissa.
1000mL of pure water, 1g of ammonium chloride, 1g of dipotassium hydrogen phosphate, 0.25g of magnesium sulfate, 0.25g of potassium chloride, 0.002g of ferrous sulfate and 0.3g of yeast extract are weighed to prepare nutrient solution, and the nutrient solution is sterilized at high temperature for later use.
Taking 800 g-1000 g of pond sludge of Anhui university, diluting with 1L of river water for three times, stirring, standing for 15min, filtering with double-layer gauze, and taking filtrate for later use.
Weighing 500mL of nutrient solution into a 1L triangular flask, adding 15mL of 1g/L Gemini ester group quaternary ammonium salt aqueous solution, adding 5mL of activated sludge solution, shaking uniformly, covering a cotton plug, and placing in a constant temperature shaking table at 25 ℃ and 200r/min for shaking for 72h to obtain the culture solution.
Weighing 500mL of nutrient solution into a 1L triangular flask, adding 15mL of 1g/L gemini esterquat aqueous solution, adding 5mL of culture solution obtained in the step 4, shaking uniformly, covering a cotton plug, and placing in a constant-temperature shaking table at 25 ℃ and 200r/min for shaking for 72h to obtain the domestication solution.
Measuring 500mL of nutrient solution into a 1L triangular flask, adding 15mL of 1g/L of gemini esterquat aqueous solution, adding 5mL of the domestication solution obtained in the step 4, shaking uniformly, covering a cotton plug, placing in a constant temperature shaking table at 25 ℃ and 200r/min, shaking for 5min, taking as a degradation zero, sampling at certain time intervals, and testing the degradation degree.
Q in FIGS. 8 and 9m-2-m、Qm-4-mThe degradation kinetics curve shows that the concentrations of the eight quaternary ammonium salts are all less than 1% of the original concentration after 24 hours of sludge degradation, and the eight quaternary ammonium salts can be degraded by more than 50% in the first 6 hours. Q14-2-14May be associated with too long unstable segments.
According to the results of the antibacterial kinetics, the conclusion can be drawn that the quaternary ammonium salt material prepared by the invention can kill bacteria by more than 99% before being completely degraded, and has extremely high degradation characteristics.
It should be understood that the above examples are only for clarity of illustration and are not intended to limit the embodiments. Any person skilled in the art may, using the teachings disclosed above, change or modify the equivalent embodiments with equivalent changes. However, any simple modification, equivalent change and modification of the above embodiments according to the technical essence of the present invention are within the protection scope of the technical solution of the present invention.
Claims (9)
1. A method for synthesizing novel degradable quaternary ammonium salt with high antibacterial activity is characterized by comprising the following steps: firstly, reacting chloroacetyl chloride with ethylene glycol, butanediol or hexanediol to synthesize intermediates with the length N of a spacer group of 2, 4 and 6 respectively, and then reacting the intermediates with N, N-dimethyloctane-1-amine, N-dimethyldecane-1-amine, N-dimethyldodecane-1-amine or N, N-dimethyltetradecane-1-amine with the length m of a hydrophobic alkyl chain of 8, 10, 12 and 14 respectively to obtain the gemini ester group quaternary ammonium salt with the length m of the hydrophobic alkyl chain and the length N of the spacer group.
2. The method of synthesis according to claim 1, characterized in that: the resulting gemini esterquat was designated as Qm-n-mWhen m is 8, 10, 12 or 14, n is 2, 4 or 6, namely the obtained gemini esterquat is Q8-2-8、Q10-2-10、Q12-2-12、Q14-2-14、Q8-4-8、Q10-4-10、Q12-4-12、Q14-4-14，Q8-6-8、Q10-6-10、Q12-6-12And Q14-6-14One kind of (1).
3. The method of synthesis according to claim 1, comprising the steps of:
step 1, adding ethylene glycol, butanediol or hexanediol into a three-neck flask, adding chloroacetic acid, dropwise adding chloroacetyl chloride, carrying out reflux reaction at 50-60 ℃ for 2-4h, pouring the obtained reaction system into ice water, and carrying out suction filtration to obtain a crude product; finally washing the product with saturated brine and sodium carbonate solution, and vacuum drying at 50-80 deg.C to obtain intermediate ethane-1, 2-diylbis (2-chloroacetic acid), butane-1, 4-diylbis (2-chloroacetic acid) or hexane-1, 6-diylbis (2-chloroacetic acid);
and 2, adding N, N-dimethyloctane-1-amine, N-dimethyldecane-1-amine, N-dimethyldodecane-1-amine or N, N-dimethyltetradecane-1-amine into a three-necked flask, adding acetone or dichloromethane serving as a solvent, dropwise adding the intermediate obtained in the step 1, carrying out reflux reaction at 40-50 ℃ for 6-24h, carrying out suction filtration, carrying out recrystallization purification on the product, and carrying out vacuum drying at 50-80 ℃ to obtain the product, namely the diester-based quaternary ammonium salt.
4. The method of synthesis according to claim 3, characterized in that: in the step 1, the molar ratio of ethylene glycol, butanediol or hexanediol to chloroacetic chloride is 1: 2-3, and the molar ratio of ethylene glycol, butanediol or hexanediol to chloroacetic acid is 1: 1.
5. The method of synthesis according to claim 3, characterized in that: in the step 2, the molar ratio of the N, N-dimethyloctane-1-amine, the N, N-dimethyldecane-1-amine, the N, N-dimethyldodecane-1-amine or the N, N-dimethyltetradecane-1-amine to the intermediate is 2: 4-7.
6. The method of synthesis according to claim 3, characterized in that: in the step 1, the dropping speed of the chloracetyl chloride is 1-2 seconds per drop.
7. The method of synthesis according to claim 3, characterized in that: in step 2, the dropping speed of the intermediate is 1-2 seconds per drop.
8. A gemini esterquat produced by the synthetic method of any one of claims 1 to 7.
9. Use of the gemini esterquat as claimed in claim 8 as a degradable antibacterial material.
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